Golimumab (Simponi and Simponi Aria)

Number: 0790

Commercial CPB  |  Medicare CPB

 

Policy

Note: Simponi Aria (golimumab intravenous) requires precertification:

Commercial plans: Precertification of intravenous golimumab (Simponi Aria) is required of all Aetna participating providers and members in applicable plan designs.  For precertification intravenous golimumab, call (866) 752-7021 or fax (888) 267-3277.

Medicare Part B plans: Precertification of intravenous golimumab (Simponi Aria) is required of participating providers and members in applicable Medicare Part B plan designs. For precertification of intravenous golimumab, call (866) 503-0857, or fax (844) 268-7263.

Note: For commercial plans, Site of Care Utilization Management Policy applies to Simponi Aria. For information on site of service for Simponi Aria infusions, see Utilization Management Policy on Site of Care for Specialty Drug Infusions.

Intravenous golimumab (Simponi Aria)

1. Criteria for Initial Approval

   Aetna considers intravenously administered golimumab (Simponi Aria) medically necessary for the following indications, where the member has had a documented negative TB test (which can include a tuberculosis skin test (PPD), an interferon-release assay (IGRA), or a chest x-ray)Footnote1* within 6 months of initiating therapy for persons who are naive to biologic DMARDs or targeted synthetic DMARDs associated with an increased risk of TB: 

   1. Moderately to severely active rheumatoid arthritis (RA)

      1. For members who have previously received a biologic or targeted synthetic DMARD (e.g. Rinvoq, Xeljanz) indicated for moderately to severely active rheumatoid arthritis; the requested medication must be prescribed in combination with methotrexate unless the member has a clinical reason not to use methotrexate (see Appendix A) or leflunomide; or
      2. For treatment of moderately to severely active RA when all of the following criteria are met:
         
         

         1. Member meets either of the following criteria:

            1. Member has been tested for either of the following biomarkers and the test was positive:

               1. Rheumatoid factor (RF); or
               2. Anti-cyclic citrullinated peptide (anti-CCP); or

            2. Member has been tested for all of the following biomarkers:

               1. RF; and
               2. Anti-CCP; and
               3. C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR); and
                  
         2. Member is prescribed the requested medication in combination with methotrexate or leflunomide or has a clinical reason not to use methotrexate or leflunomide; and
         3. Member meets either of the following criteria:
            
            
            1. Member has experienced an inadequate response to at least a 3-month trial of methotrexate despite adequate dosing (i.e., titrated to at least 15 mg/week); or
            2. Member has an intolerance or contraindication to methotrexate (see Appendix A);

   2. Active psoriatic arthritis (PsA)

      When member meets criteria in CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators or CPB 0658m - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators [Medicare];

   3. Active ankylosing spondylitis (AS)

      1. For members who have previously received a biologic indicated for active ankylosing spondylitis; or
      2. For treatment of active ankylosing spondylitis when any of the following criteria is met:
         
         
         1. Member has experienced an inadequate response to at least two non-steroidal anti-inflammatory drugs (NSAIDs); or
         2. Member has an intolerance or contraindication to two or more NSAIDs (see Appendix B);
            

   4. Active articular juvenile idiopathic arthritis (JIA)

      1. For members who have previously received a biologic or targeted synthetic DMARD indicated for active articular juvenile idiopathic arthritis; or
      2. For treatment of active articular juvenile idiopathic arthritis when any of the following criteria is met: 
         
         
         1. The member has had an inadequate response to methotrexate or another non-biologic DMARD administered at an adequate dose and duration; or
         2. The member has risk factors (see Appendix C) and the member also meets one of the following:
            
            
            1. High-risk joints are involved (e.g., cervical spine, wrist, or hip); or
            2. High disease activity; or
            3. Are judged to be at high risk for disabling joint disease.

   Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).

2. Continuation of Therapy

   Aetna considers continuation of intravenous golimumab (Simponi Aria) therapy medically necessary for the following indications:

   1. Moderately to severely active rheumatoid arthritis (RA)

      For all members (including new members) who are using the requested medication for moderately to severely active rheumatoid arthritis and who achieve or maintain a positive clinical response as evidenced by disease activity improvement of at least 20% from baseline in tender joint count, swollen joint count, pain, or disability;

   2. Active psoriatic arthritis (PsA)

      When member meets criteria in CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators or CPB 0658m - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators [Medicare];

   3. Active ankylosing spondylitis (AS)

      For all members (including new members) who are using the requested medication for active ankylosing spondylitis and who achieve or maintain a positive clinical response with the requested medication as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:

      1. Functional status; or
      2. Total spinal pain; or
      3. Inflammation (e.g., morning stiffness);

   4. Active articular juvenile idiopathic arthritis

      For all members (including new members) who are using the requested medication for active articular juvenile idiopathic arthritis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:

      1. Number of joints with active arthritis (e.g., swelling, pain, limitation of motion); or
      2. Number of joints with limitation of movement; or
      3. Functional ability.

Subcutaneous golimumab (Simponi)

1. Criteria for Inital Approval

   Aetna considers subcutaneously administered golimumab (Simponi) medically necessary for the following indications, where the member has a documented negative TB test (which can include a tuberculosis skin test (PPD), an interferon-release assay (IGRA), or a chest x-ray)Footnotes for TB test* within 6 months of initiating therapy for persons who are naive to biologic DMARDs or targeted synthetic DMARDs associated with an increased risk of TB:

   1. Moderately to severely active rheumatoid arthritis (RA)

      1. For members who have previously received a biologic or targeted synthetic DMARD (e.g., Rinvoq, Xeljanz) indicated for moderately to severely active rheumatoid arthritis; the requested medication must be prescribed in combination with methotrexate or leflunomide unless the member has a clinical reason not to use methotrexate (see Appendix A) or leflunomide; or
      2. For treatment of moderately to severely active RA when all of the following criteria are met:
         
         

         1. Member meets either of the following criteria:

            1. Member has been tested for either of the following biomarkers and the test was positive:

               1. Rheumatoid factor (RF); or
               2. Anti-cyclic citrullinated peptide (anti-CCP); or

            2. Member has been tested for all of the following biomarkers:

               1. RF; and
               2. Anti-CCP; and
               3. C-reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR); and
                  
         2. Member is prescribed the requested medication in combination with methotrexate or leflunomide or has a clinical reason not to use methotrexate or leflunomide; and
         3. Member meets either of the following criteria:
            
            
            1. Member has experienced an inadequate response to at least a 3-month trial of methotrexate despite adequate dosing (i.e., titrated to at least 15 mg/week); or
            2. Member has an intolerance or contraindication to methotrexate (see Appendix A);

   2. Active psoriatic arthritis (PsA) 

      When member meets criteria in CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators or CPB 0658m - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators [Medicare];

   3. Active ankylosing spondylitis (AS) and active axial spondyloarthritis

      1. For members who have previously received a biologic indicated for active ankylosing spondylitis or active axial spondyloarthritis; or
      2. For treatment of active ankylosing spondylitis and active axial spondyloarthritis when any of the following criteria is met:
         
         
         1. Member has experienced an inadequate response to at least two non-steroidal anti-inflammatory drugs (NSAIDs); or
         2. Member has an intolerance or contraindication to two or more NSAIDs (see Appendix B);

   4. Moderately to severely active ulcerative colitis (UC)

      1. For members who have previously received a biologic or targeted synthetic drug (e.g., Xeljanz) indicated for moderately to severely active ulcerative colitis; or
      2. For the treatment of moderately to severely active UC when the member has had an inadequate response, intolerance or contraindication to at least one conventional therapy option (see Appendix D).

   Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).

2. Continuation of Therapy

   1. Moderately to severely active rheumatoid arthritis (RA)

      For all members (including new members) who are using the requested medication for moderately to severely active rheumatoid arthritis and who achieve or maintain a positive clinical response as evidenced by disease activity improvement of at least 20% from baseline in tender joint count, swollen joint count, pain, or disability;

   2. Active psoriatic arthritis (PsA)

      When member meets criteria in CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators or CPB 0658m - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators [Medicare];

   3. Active ankylosing spondylitis (AS) and active axial spondyloarthritis

      For all members (including new members) who are using the requested medication for active ankylosing spondylitis or active axial spondyloarthritis and who achieve or maintain a positive clinical response with the requested medication as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:

      1. Functional status; or
      2. Total spinal pain; or
      3. Inflammation (e.g., morning stiffness);

   4. Moderately to severely active ulcerative colitis (UC)

      1. For all members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain remission; or
      2. For all members (including new members) who are using the requested medication for moderately to severely active ulcerative colitis and who achieve or maintain a positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition when there is improvement in any of the following from baseline:
         
         
         1. Stool frequency; or
         2. Rectal bleeding; or
         3. Urgency of defecation; or
         4. C-reactive protein (CRP); or
         5. Fecal calprotectin (FC); or
         6. Endoscopic appearance of the mucosa; or
         7. Improvement on a disease activity scoring tool (e.g., Ulcerative Colitis Endoscopic Index of Severity [UCEIS], Mayo score).

Footnote1* If the screening test for TB is positive, there must be further testing to confirm there is no active disease. Do not administer the requested medication to members with active TB infection. If there is latent disease, TB treatment must be started before initiation of the requested medication. 

See also:

• CPB 0314 - Rituximab or CPB 0314m - Rituximab [Medicare],
• CPB 0315 - Etanercept,
• CPB 0341 - Infliximab or CPB 0341m - Infliximab [Medicare],
• CPB 0655 - Adalimumab (Humira), and
• CPB 0720 - Abatacept (Orencia) or CPB 0720m - Abatacept (Orencia) [Medicare].

Dosage and Administration

Note: Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines. Below includes dosing recommendations as per the FDA-approved prescribing information.

Simponi Aria (golimumab intravenous)

• Simpoini Aria (golimumab) is available for intravenous injection as 50 mg/4 mL (12.5 mg/mL) solution in a single-dose vial. Simponi Aria solution for intravenous infusion should be diluted by a healthcare professional.

• Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

  The Simponi Aria dosage regimen is 2 mg/kg given as an intravenous infusion over 30 minutes at weeks 0 and 4, then every 8 weeks thereafter. For persons with rheumatoid arthritis (RA), Simponi Aria should be given in combination with methotrexate. The efficacy and safety of switching between intravenous and subcutaneous formulations and routes of administration have not been established.

• Polyarticular juvenile idiopathic arthritis

  The Simponi Aria dosage regimen, based on body surface area (BSA), is 80 mg/m² given as an intravenous infusion over 30 minutes at weeks 0 and 4, and every 8 weeks thereafter.

Source: Janssen Biotech, 2021

Simponi (golimumab subcutaneous)

• Simponi (golimumab) is available for subcutaneous injection as 50 mg/0.5 mL and 100 mg/mL in a single-dose prefilled syringe or single-dose prefilled SmartJect autoinjector. Simponi is intended for use under the guidance and supervision of a healthcare provider. After proper training in subcutaneous injection technique, a person may self-inject with Simponi if a physician determines that it is appropriate. 

• Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis

  The Simponi dose regimen is 50 mg administered by subcutaneous injection once a month. For persons with rheumatoid arthritis (RA), Simponi should be given in combination with methotrexate. For persons with psoriatic arthritis (PsA) or ankylosing spondylitis (AS), Simponi may be given with or without methotrexate or other nonbiologic Disease-Modifying Antirheumatic Drugs (DMARDs). For persons with RA, PsA, or AS, corticosteroids, non-biologic DMARDs, and/or NSAIDs may be continued during treatment with Simponi.

• Ulcerative Colitis (moderate to severe)

  The recommended Simponi induction dosage regimen is a 200 mg subcutaneous injection at Week 0, followed by 100 mg at Week 2, and then maintenance therapy with 100 mg every 4 weeks.

Source: Janssen Biotech, 2019

Experimental and Investigational

1. Aetna considers golimumab in combination with other biological disease-modifying antirheumatic drugs (bioDMARDs) experimental and investigational because the safety and effectiveness of these combinations has not been established.

2. Aetna considers intravenously administered golimumab experimental and investigational for Crohn's disease and for the treatment of ocular inflammatory disorders (e.g., Behcet's disease, panuveitis, posterior uveitis, and scleritis) because its effectiveness for these indications has not been established (not an all-inclusive list).

3. Aetna considers subcutaneously administered golimumab experimental and investigational for all other indications, including the following (not an all-inclusive list) because its effectiveness for these indications has not been established:

   1. Asthma
   2. Behcet's
   3. Crohn's disease
   4. Panuveitis
   5. Posterior uveitis
   6. Sarcoidosis
   7. Scleritis.

Background

Golimumab, a tumor necrosis factor (TNF) blocker, is available as Simponi (for subcutaneous injection) and Simponi Aria (for intravenous infusion). 

Golimumab, a human monoclonal antibody, inhibits the biological activity of tumor necrosis factor alpha (TNF-alpha).  Elevated TNF-alpha levels have been implicated in the pathophysiology of several chronic inflammatory diseases, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).  Tumor necrosis factor-alpha is an important mediator of the articular inflammation that is characteristic of these diseases.

Golimumab neutralizes the biologic activity of tumor necrosis factor (TNF)‐alpha by binding and blocking its interaction with cell surface TNF receptors. Elevated TNF‐alpha concentrations in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis. Tumor necrosis factor‐alpha is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.

Boyce and colleagues (2010) reviewed the literature on golimumab (GLM) and provided recommendations for the use of GLM based on the published information.  The PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, International Pharmaceutical Abstracts, and other databases, as well as the Web sites for the ACR and the European Union League Against Rheumatism, were searched for relevant articles published in English between the inception of the databases through April 2010.  Pharmacologic, pharmacokinetic, clinical, outcomes, and economic studies as well as meta-analyses, case reports, and select abstracts were eligible for inclusion.  Review articles on GLM were not used except to identify other primary papers.  A total of 7 clinical studies were identified and used to evaluate the efficacy and tolerability of GLM: 5 in patients with RA (4 subcutaneous administration and 1 intravenous administration), 1 in patients with PsA (subcutaneous), and 1 in patients with AS (subcutaneous).  In MTX-naive patients with RA, the number of patients satisfying the ACR20 response criteria (greater than 20 % improvement in ACR response rate) at 24 weeks was significantly higher for the GLM + MTX groups than for the MTX-only groups (62 % versus 49 %, respectively; p < 0.05).  In patients with active RA despite MTX therapy, ACR20 responses at 14 to 16 weeks were significantly higher for the combined GLM + MTX groups than for the MTX groups (50 % to 79 % versus 33 % to 37 %, respectively; p < 0.001).  Golimumab was more effective than placebo, both with and without MTX, in patients with RA and a history of treatment with 1 or 2 TNF-α inhibitors (ACR20 at 14 weeks, 35 % to 37 % versus 18 %, respectively; p < 0.001).  Studies of other TNF-α inhibitors reported ACR20 responses in 53 % to 59 % of patients with active RA at 24 weeks.  Golimumab was also more effective than placebo at 24 weeks in patients with PsA (ACR20, 52 % to 61 % versus 12 %, respectively; p < 0.001) (ASAS40 [40 % improvement based on Assessment in Ankylosing Spondylitis International Working Group criteria], 44 % to 54 % versus 15 %, respectively; p < 0.001).  Studies of other TNF-α inhibitors reported ACR20 responses at 24 weeks in 55 % to 57 % of patients with PsA and ASAS40 responses in 46 % to 47 % of patients with AS.  The incidence of any adverse effect appeared to be comparable in the GLM (61.2 % to 93.9 %) and placebo groups (59.3 % to 85.3 %), but withdrawals because of adverse effects were higher in the GLM groups (0 % to 12.1 %) than in the placebo groups (0 % to 5.9 %).  The incidence of serious infections was comparable for GLM (0 % to 4.4 %) and placebo (0.8 % to 3.5 %).  The most frequently reported adverse effects in the GLM groups were injection-site reactions (2.7 % to 37.1 %), nausea (2.7 % to 22.9 %), headache (3.8 % to 21.2 %), nasopharyngitis (1.9 % to 15.0 %), and upper respiratory tract infections (5.7 % to 13.8 %).  The authors concluded that based on the results of the studies included in this review, GLM appeared to be more effective than placebo in patients with RA, PsA, or AS.  Clinical studies have not directly compared GLM with other TNF-α inhibitors.  However, according to the available efficacy and tolerability data, GLM should be considered as the first or second TNF-α inhibitor for the treatment of PsA or AS and as the second or possibly first TNF-α inhibitor in combination with MTX for the treatment of RA.

Golimumab for Subcutaneous Injection (Simponi)

U.S. Food and Drug Administration (FDA)-Approved Indications for Simponi (for subcutaneous injection)

• Moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate
• Active psoriatic arthritis (PsA), alone or in combination with methotrexate 
• Active ankylosing spondylitis (AS)
• Moderately to severely active ulcerative colitis (UC) who have demonstrated corticosteroid dependance or who have had an inadequate response to or failed to tolerate oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine for inducing and maintaining clinical response, improving endoscopic appearance of the mucosa during induction, inducing clinical remission, and achieving and sustaining clinical remission in induction responders

Compendial Use for Simponi (for subcutaneous use)

• Axial spondyloarthritis

Subcutaneous golimumab is available as Simponi (Janssen Biotech, Inc.), a tumor necrosis factor (TNF) blocker. Golimumab is a human monoclonal antibody that binds to both the soluble and transmembrane bioactive forms of human TNFα. This interaction prevents the binding of TNFα to its receptors, thereby inhibiting the biological activity of TNFα (a cytokine protein). Elevated TNFα levels in the blood, synovium, and joints have been implicated in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. TNFα is an important mediator of the articular inflammation that is characteristic of these diseases (Janssen, 2019).

Golimumab (Simponi) (Janssen Biotech Inc., formerly Centocor Ortho Biotech Inc.) for subcutaneous use was approved by the U.S. FDA on April 24, 2009 for adults with moderately-to-severely active rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis. Simponi is intended for use in combination with methotrexate (MTX) in patients with rheumatoid arthritis.  It also may be used with or without MTX for active psoriatic arthritis and alone in patients with active ankylosing spondylitis, a chronic inflammatory arthritis of the spine.  For patients with rheumatoid arthritis, active psoriatic arthritis, or active ankylosing spondylitis, corticosteroids, non-biologic disease-modifying anti-rheumatic drugs (DMARDs), and/or non-steroidal anti-inflammatory drugs (NSAIDs) may be continued during treatment with golimumab. 

The label for Simponi includes a black box warning for risk of serious infections and malignancy. Patients treated with Simponi are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, or parasitic organisms including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, egionellosis, listeriosis, pneumocystosis, and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections; therefore, the concomitant use of Simponi and these biologic products is not recommended. Treatment with Simponi should not be initiated in patients with an active infection, including clinically important localized infections. Patients greater than 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants such as corticosteroids or methotrexate may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating Simponi in patients with chronic or recurrent infection, who have been exposed to tuberculosis, with a history of an opportunistic infection, and who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomy. Other labeled warning and precautions include hepatitis B reactivation, new onset or worsening congestive heart failure, demyelinating disorders, lupus-like syndrome, and hypersensitivity reactions. Live vaccines/therapeutic infectious agents should be avoided with with Simponi.

Most common adverse reactions (incidence > 5%) are upper respiratory tract infection, nasopharyngitis, and injection site reactions.

Subcutaneous Golimumab (Simponi) for Ankylosing Spondylitis and Axial Spondyloarthritis

Ankylosing spondylitis (AS) is a form of arthritis known as spondyloarthritis, which is a group of closely linked rheumatic diseases that can cause pain in the spine and joints as well as ligaments and tendons. UpToDate defines spondyloarthritis as a group of arthritis-associated conditions. One of the associated conditions include axial spondyloarthritis (axSpA), which is a potentially disabling inflammatory arthritis that typically affects the spine; however, may also affect joints in the arms and legs. Symptoms typically begin before the age of 45. Those with axSpA can be further classified into 2 subtypes such as ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA). Individuals affected by AS exhibit radiographic abnormalities consistent with sacrolitis, whereas, findings are absent or minimal on plain radiography for those with nr-axSpA. Individuals with nr-axSpA may have evidence of active inflammation of the sacroiliac (SI) joints on MRI findings (e.g., bone marrow edema of the joints). The diagnosis of axSpA, including AS and nr-axSpA, should be considered in persons with continuous chronic back pain prior to age 45. Per UpToDate, "there is no single historical feature, physical finding, laboratory test, or imaging study with sufficient specificity by itself to establish the diagnosis without the presence of additional abnormalities. Thus, the presence of a combination of features together with the exclusion of other diagnoses that may explain such symptoms or findings is necessary to arrive at an accurate diagnosis"  (Yu and van Tubergen, 2018).

The safety and efficacy of golimumab in AS were evaluated in a multi-center, randomized, double-blind placebo-controlled trial.  Adult patients (n = 356) with active AS according to modified New York criteria for at least 3 months (study AS) with symptoms of active disease (defined as a Bath AS Disease Activity Index (BASDAI) of 4 or greater and visual analogue scale (VAS) for total back pain of 4 or greater, on a scale of 0 to 10 cm) despite current or previous NSAID therapy.  Patients were excluded if they were previously treated with a biologic TNF-blocker or if they had complete ankylosis of the spine.  Patients were randomly assigned to placebo (n = 78), 50-mg golimumab (n = 138), or 100-mg golimumab (n = 140) administered subcutaneously every 4 weeks.  Patients were allowed to continue stable doses of concomitant MTX, SSZ, HCQ, low dose corticosteroids (equivalent to less than 10 mg of prednisone a day), and/or NSAIDs during the trial.  The use of other DMARDs including cytotoxic agents or other biologics was prohibited.  The primary endpoint was the percentage of patients achieving as Assessment in Ankylosing Spondylitis (ASAS) 20 response at week 14.  Placebo-controlled efficacy data were collected and analyzed through week 24.  The median duration of ankylosing spondylitis disease was 5.6 years, median duration of inflammatory back pain was 12 years, 83 % were HLA-B27 positive, 24 % had prior joint surgery or procedure, and 55 % received at least 1 DMARD in the past.  During the trial, the use of concomitant DMARDS and/or NSAIDS was: MTX (20 %), SSZ (26 %), HCQ (1 %), low-dose oral steroids (16 %), and NSAIDs (90 %).  Golimumab, with or without DMARDs, resulted in a significant improvement in signs and symptoms, compared with placebo, with or without DMARDs, as demonstrated by the proportion of patients with an ASAS 20 response at week 14.  There was no clear evidence of improved ASAS response with the higher golimumab dose group (100 mg) compared to the lower dose group (50 mg).

The safety and efficacy of golimumab in active AS were evaluated in the Go-Raise study.  Patients with active AS, a BASDAI score of 4 or greater, and a back pain score of 4 or greater were randomly assigned in a 1.8:1.8:1 ratio to receive subcutaneous injections of golimumab (50-mg or 100-mg) or placebo every 4 weeks.  The primary endpoint was the proportion of patients with at least 20 % improvement in the ASAS20 criteria at week 14.  At randomization, 138, 140, and 78 patients were assigned to the 50-mg, 100-mg, and placebo groups, respectively.  After 14 weeks, 59.4 %, 60.0 %, and 21.8 % of patients, respectively, were ASAS20 responders (p < 0.001).  A 40 % improvement in the ASAS criteria at week 24 occurred in 43.5 %, 54.3 %, and 15.4 % of patients, respectively.  Patients receiving golimumab also showed significant improvement in the physical and mental component summary scores of the SF-36 Health Survey, the Jenkins Sleep Evaluation Questionnaire score, the BASDAI score, and the Bath AS Functional Index score, but not the Bath AS Metrology Index score.  Through week 24, 85.6 % of golimumab-treated patients and 76.6 % of patients in the placebo group had 1 or more adverse event, and 5.4 % and 6.5 % of patients, respectively, had 1 or more serious adverse event.  Eight golimumab-treated patients and 1 placebo-treated patient had markedly abnormal liver enzyme values, which were transient.  Golimumab was effective and well-tolerated in a large cohort of patients with AS during a 24-week study period (Inman et al, 2008).

Per the Prescribing Information (PI) (Janssen Biotech, 2018), subcutaneous golimumab (Simponi) is indicated for the treatment of active ankylosing spondylitis (AS). Although axial spondyloarthritis (active nonradiographic) is not listed as an indication of Simponi in the PI, it is included in the compendia as an off-label indication, as well as recommended in UpToDate (Yu and van Tubergen, 2019) for individuals who have had an inadequate resonse to two different nonsteroidal antiinflammatory drugs (NSAIDS) used consecutively.

Subcutaneous Golimumab (Simponi) for Psoriatic Arthritis

The safety and efficacy of golimumab in active PsA were evaluated in a multi-center, randomized, double-blind placebo-controlled trial in 405 adult patients with moderately-to-severely active PsA with at least 3 swollen joints and 3 tender joints despite NSAID or DMARD therapy (study PsA).  Patients in this study had a diagnosis of active PsA for at least 6 months with a qualifying psoriatic skin lesion of at least 2 cm in diameter.  Previous treatment with a biologic TNF-blocker was not permitted.  Patients were randomly assigned to placebo (n = 113), 50-mg golimumab (n = 146), or 100-mg golimumab (n = 146) given subcutaneously every 4 weeks.  Patients were allowed to receive stable doses of concomitant MTX (25 mg or less/week), low-dose oral corticosteroids (equivalent to 10 mg or less of prednisone/day), and/or NSAIDS during the trial.  The use of other DMARDs including sulfasalazine (SSZ), hydroxychloroquine (HCQ), cytotoxic agents, or other biologics was prohibited.  The primary endpoint was the percentage of patients achieving ACR 20 response at week 14.  Placebo-controlled efficacy data were collected and analyzed through week 24.  Patients with each subtype of active PsA were enrolled, including polyarticular arthritis with no rheumatoid nodules (43 %), asymmetric peripheral arthritis (30 %), distal inter-phalangeal (DIP) joint arthritis (15 %), spondylitis with peripheral arthritis (11 %), and arthritis mutilans (1 %).  The median duration of active psoriatic arthritis disease was 5.1 years, 78 % of patients received at least 1 DMARD in the past, approximately 48 % of patients received MTX, and 16 % received low-dose oral steroids.  Golimumab with or without MTX resulted in significant improvement in signs and symptoms compared with placebo with or without MTX as demonstrated by the proportion of patients with an ACR 20 response at week 14.  There was no clear evidence of improved ACR response with the higher golimumab dose group (100 mg) compared to the lower dose group (50 mg).  ACR responses observed in the golimumab-treated groups were similar with or without concomitant MTX.  Similar ACR 20 responses at week 14 were observed in patients with different active PsA subtypes.  Treatment with golimumab resulted in improvement in enthesitis and skin manifestations in patients with active PsA.  However, the safety and efficacy of golimumab in the treatment of patients with plaque psoriasis has not been established. 

Kavanaugh et al (2009) assessed the safety and efficacy of golimumab in adult patients with active PsA who had at least 3 swollen and 3 tender joints and active psoriasis.  Patients were randomly assigned to receive subcutaneous injections of placebo (n = 113), 50-mg golimumab (n = 146), or 100-mg golimumab (n = 146) every 4 weeks through week 20.  Efficacy assessments through week 24 included ACR20, the Psoriasis Area and Severity Index (PASI) in patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline, the Short Form 36 Health Survey (SF-36), HAQ-DI, the Nail Psoriasis Severity Index (NAPSI), the physician's global assessment of psoriatic nail disease, and enthesitis (using the PsA-modified Maastricht Ankylosing Spondylitis Enthesitis Score [MASES] index).  At week 14, 48 % of all patients receiving golimumab, 51 % of patients receiving 50-mg golimumab, and 45 % of patients receiving 100-mg golimumab achieved an ACR20 response (the primary endpoint), compared with 9 % of patients receiving placebo (p < 0.001 for all comparisons).  Among the 74 % of patients in whom at least 3 % of the body surface area was affected by psoriasis at baseline, 40 % of those in the 50-mg golimumab group and 58 % of those in the 100-mg golimumab group had at least 75 % improvement in the PASI at week 14 (major secondary endpoint), compared with 3 % of placebo-treated patients (p < 0.001 for both doses).  Significant improvement was observed for other major secondary endpoints (the HAQ and the SF-36), the NAPSI, the physician's global assessment of psoriatic nail disease, and the PsA-modified MASES index in each golimumab group compared with placebo.  This efficacy was maintained through week 24.  Golimumab was generally well-tolerated.  The authors concluded that treatment with golimumab at doses of 50-mg and 100-mg significantly improved active PsA and associated skin and nail psoriasis through week 24.

Subcutaneous Golimumab (Simponi) for Rheumatoid Arthritis

The safety and effectiveness of golimumab in RA were evaluated in 3 multi-center, randomized, double-blind, controlled trials (studies RA-1, RA-2, and RA-3).  Patients (n = 1,542) 18 years of age or older with moderately- to-severely active RA diagnosed according to the American College of Rheumatology (ACR) criteria at least 3 months prior to the study, with at least 4 swollen and 4 tender joints were included.  Golimumab was administered subcutaneously at doses of 50 mg or 100 mg every 4 weeks.  Double-blinded controlled efficacy data were collected and analyzed through week 24.  Patients were allowed to continue stable doses of concomitant low-dose corticosteroids (equivalent to 10 mg or less of prednisone/day) and/or NSAIDs and patients may have received oral MTX during the trials.  The primary endpoint in study RA-1 and study RA-2 was the percentage of patients achieving an ACR response at week 14 and primary endpoint in study RA-3 was the percentage of patients achieving an ACR 50 response at week 24.  In studies RA-1, RA-2, and RA3, the median duration of rheumatoid arthritis disease was 9.4, 5.7, and 1.2 years; and 99 %, 75 %, and 54 % of the patients used at least 1 DMARD in the past, respectively.  Approximately 77 % and 57 % of patients received concomitant NSAIDs and low-dose corticosteroids, respectively, in the 3 pooled RA trials.  A greater percentage of patients treated with the combination of golimumab and MTX achieved ACR responses at week 14 (studies RA-1 and RA-2) and week 24 (studies RA-1, RA-2, and RA-3) versus patients treated with MTX alone.  There was no clear evidence of improved ACR response with the higher golimumab dose group (100 mg) compared to the lower dose group (50 mg).  In the subset of patients who received golimumab in combination with MTX (n = 103) in study RA-1, the proportion of patients achieving ACR 20, 50 and 70 responses at week 14 were 40 %, 18 %, and 13 %, respectively, compared with 17 %, 6 %, and 2 %, respectively, in the placebo plus MTX group (n = 107).  ACR responses were observed in 38 % of patients treated with the combination of 50-mg golimumab and MTX at the first assessment (week 4) after the initial golimumab administration.  In studies RA-1 and RA-2, the 50-mg golimumab groups demonstrated a greater improvement compared to the control groups in the change in mean Health Assessment Questionnaire Disability Index (HAQ-DI) score from baseline to week 24: 0.25 versus 0.05 in RA-1, 0.47 versus 0.13 in RA-2, respectively.  Also, in studies RA-1 and RA-2, the 50-mg golimumab groups had a greater proportion of HAQ responders (change from baseline greater than 0.22) compared to the control groups at week 24: 44 % versus 28 %, 65 % versus 35 %, respectively.

Guidance from the National Institute for Health and Clinical Excellence (NICE, 2011) recommended the use of golimumab in combination with methotrexate as an option for the treatment of rheumatoid arthritis in adults whose rheumatoid arthritis has responded inadequately to conventional DMARDs only, including methotrexate, in persons who have undergone trials of 2 DMARDs, including methotrexate (unless contraindicated).  A trial of a DMARD is defined as being normally of 6 months, with 2 months at standard dose, unless significant toxicity has limited the dose or duration of treatment.

Kay et al (2008) assessed the safety, efficacy, and pharmacology of subcutaneous administration of golimumab in patients with active RA despite treatment with MTX.  Patients were randomly assigned in a double-blinded manner to receive injections of placebo plus MTX or 50-mg or 100-mg golimumab every 2 or 4 weeks plus MTX through week 48.  Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20.  The primary endpoint was the proportion of patients meeting achieving an ACR 20 response at week 16.  The study was powered to detect a difference in the primary endpoint when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo.  The primary endpoint was attained.  Sixty-one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR 20 response at week 16 compared with 37 % of patients in the placebo plus MTX group (p = 0.010).  In addition, 79 % of patients in the group receiving 100-mg golimumab every 2 weeks achieved an ACR 20 response (p < 0.001 versus placebo).  Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9 % of patients in the combined golimumab groups and in 6 % of patients in the placebo group.  The authors concluded that golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well-tolerated in patients with an inadequate response to MTX.

The phase III Go-Forward study (Keystone et al, 2009) examined the safety and efficacy of golimumab in patients with active RA despite MTX therapy.  Patients were randomly assigned in a 3:3:2:2 ratio to receive placebo injections plus MTX capsules (group 1, n = 133), 100-mg golimumab injections plus placebo capsules (group 2, n = 133),  50-mg golimumab injections plus MTX capsules (group 3, n = 89), or 100-mg golimumab injections plus MTX capsules (group 4, n = 89).  Injections were administered subcutaneously every 4 weeks.  The co-primary endpoints were the proportion of patients achieving an ACR20 response at week 14 and the change from baseline in the HAQ-DI score at week 24.  The proportion of patients who achieved an ACR20 response at week 14 was 33.1 % in the placebo plus MTX group, 44.4 % (p = 0.059) in the 100-mg golimumab plus placebo group, 55.1 % (p = 0.001) in the 50-mg golimumab plus MTX group, and 56.2 % (p < 0.001) in the 100-mg golimumab plus MTX group.  At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p < 0.001), and 0.50 (p < 0.001), respectively.  During the placebo-controlled portion of the study (through week 16), serious adverse events occurred in 2.3 %, 3.8 %, 5.6 %, and 9.0 % of patients and serious infections occurred in 0.8 %, 0.8 %, 2.2 %, and 5.6 %, respectively.  The authors concluded that the addition of golimumab to MTX in patients with active RA despite MTX significantly reduced the signs and symptoms of RA and improved physical function.

The American College of Rheumatology (ACR) conducted a systematic review to synthesize the evidence for the benefits and harms of various treatment options. Their goal was to develop evidence-based, pharmacologic treatment guideline for rheumatoid arthritis. The 2015 American College of Rheumatology Guidelines for the Treatment of Rheumatoid Arthritis provided “strong” recommendations for established RA and symptomatic early RA.

For established RA, the guidelines state “if the disease activity is low, in patients who have never taken a DMARD, the recommendation is to use DMARD monotherapy (methotrexate preferred) over TNFi”. “If disease activity remains moderate or high despite DMARD monotherapy, the recommendation is to use combination traditional [conventional] DMARDs or add a TNFi or a non-TNF biologic or tofacitinib (all choices with or without methotrexate, in no particular order of preference), rather than continuing DMARD monotherapy alone”. Recommendations for patients with symptomatic early RA state that “if disease activity is low, in patients who have never taken a DMARD, use DMARD monotherapy (methotrexate preferred) over double or triple therapy”.  “If disease activity remains moderate or high despite DMARD monotherapy (with our without glucocorticoids), use combination DMARDs or a TNFi or a non-TNF biologic (all choices with our without methotrexate, in no particular order of preference), rather than continuing DMARD monotherapy alone”. A strong recommendation means that the panel was confident that the desirable effects of following the recommendation outweigh the undesirable effects (or vice versa), so the course of action would apply to most patients, and only a small proportion would not want to follow the recommendation (Singh et al, 2016).

Subcutaneous Golimumab (Simponi) for Ulcerative Colitis

Sandborn et al (2014) noted that little is known about the efficacy of golimumab for treatment of ulcerative colitis (UC).  These investigators evaluated subcutaneous golimumab induction therapy in TNFα-antagonist naive patients with moderate-to-severe UC despite conventional treatment.  They integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1,064 adults with UC (Mayo score: 6 to 12; endoscopic subscore greater than or equal to 2; 774 patients in phase 3).  Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart.  The phase 3 primary endpoint was week-6 clinical response.  Secondary endpoints included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change.  In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively.  In phase 3, rates of clinical response at week 6 were 51.8 % and 55.0 % among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, versus 29.7 % among those given placebo (both p < 0.0001).  Rates of clinical remission and mucosal healing, and mean changes in IBDQ scores, were significantly greater in both golimumab groups versus the placebo group (p ≤ 0.0005, all comparisons).  Rates of serious adverse events were 6.1 % and 3.0 %, and rates of serious infection were 1.8 % and 0.5 %, in the placebo and golimumab groups, respectively.  One patient in the 400 mg/200mg group died of surgical complications from an ischio-rectal abscess.  The authors concluded that treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life, in larger percentages of patients with active UC than placebo.

Sandborn et al (2014) performed a phase 3, double-blind trial of patients who completed golimumab induction trials (PURSUIT).  Patients who responded to induction therapy with golimumab (n = 464) were randomly assigned to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52.  Patients who responded to placebo in the induction study continued to receive placebo.  Non-responders in the induction study received 100 mg golimumab.  The primary endpoint was clinical response maintained through week 54; secondary endpoints included clinical remission and mucosal healing at both weeks 30 and 54.  Clinical response was maintained through week 54 in 47.1 % of patients receiving 50 mg golimumab, 50.6 % receiving 100 mg golimumab, and 31.4 % receiving placebo (p = 0.010 and p < 0.001, respectively).  At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (28.6 % and 43.5 %) than patients given placebo (15.4 % and 26.9 %; p = 0.003 and p = 0.001, respectively) or 50 mg golimumab (23.5 % and 41.8 %, respectively).  Percentages of serious adverse events were 7.7 %, 8.4 %, and 14.3 % among patients given placebo, 50 mg, or 100 mg golimumab, respectively; percentages of serious infections were 1.9 %, 3.2 %, and 3.2 %, respectively.  Among all patients given golimumab in the study, 3 died (from sepsis, tuberculosis, and cardiac failure, all in patients who received 100 mg golimumab) and 4 developed active tuberculosis.  The authors concluded that golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderately-to-severely active UC; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54.  Safety was consistent with that reported for other TNFα-antagonists and golimumab in other approved indications.

On May 15, 2013, the FDA approved Simponi (golimumab) for the treatment of adults with moderate-to-severe ulcerative colitis that is refractory to prior treatment or requires continuous steroid therapy. The recommended dose of golimumab for ulcerative colitis is 200 mg initially administered by subcutaneous injection at Week 0, followed by 100 mg at Week 2 and then 100 mg every 4 weeks.

Golimumab for Intravenous Infusion (Simponi Aria)

U.S. Food and Drug Administration (FDA)-Approved Indications for Simponi Aria (for intravenous infusion)

• Adult patients with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate
• Active psoriatic arthritis (PsA) in patients 2 years of age and older
• Adult patients with active ankylosing spondylitis (AS)
• Active polyarticular juvenile idiopathic arthritis (pJIA) in patients 2 years of age and older

Compendial Uses

• Oligoarticular juvenile idiopathic arthritis

Intravenous golimumab is available as Simponi Aria (Janssen Biotech, Inc.) and contains the same mechanism of action and labeled black box warning and precautions as subcutaneous golimumab (Simponi). The most common adverse reactions (incidence ≥ 3%) include upper respiratory tract infection, alanine aminotransferase increased, viral infection, aspartate aminotransferase increased, neutrophil count decreased, bronchitis, hypertension, and rash. Live vaccines should not be given with Simponi Aria.

Intravenous Golimumab (Simponi Aria) for Active Psoriatic Arthritis and Active Ankylosing Spondylitis

On October 20, 2017, Janssen Biotech, Inc. announced that the U.S. FDA approved an intravenous (IV) formulation of Simponi Aria, golimumab, for the treatment of adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS). The approvals were based on two pivotal Phase 3 studies, GO-VIBRANT and GO-ALIVE, which demonstrated significant efficacy of Simponi Aria over placebo, along with a consistent safety profile across all indications.

Go-VIBRANT was a multi-center, randomized, double-blind, placebo-controlled phase-III clinical trial, which evaluated the efficacy and safety of Simponi Aria in biologic-naïve adults (18 years of age and older) with active PsA.  Criteria included a diagnosis of PsA for at least six months and had symptoms of active disease [greater than or equal to 5 swollen joints and greater than or qual to 5 tender joints and a C-reactive protein (CRP) level of greaterthan or equal to  0.6 mg/dL].  Patients who were on stable doses of methotrexate (MTX) were allowed to enroll in the study and remained on MTX during the double-blind phase.  Patients (n = 480) were randomized 1-to-1 to receive Simponi Aria 2 mg/kg (n = 241) or placebo (n = 239) as a 30-min IV infusion at Weeks 0, 4, 12 and 20.  All patients on placebo received Simponi Aria at Week 24, Week 28 and every 8 weeks thereafter through Week 52.  Patients in the Simponi Aria treatment group continued to receive Simponi Aria infusions at Week 28 and every 8 weeks through Week 52.  The primary end-point was ACR20 response at week 14.  Multiplicity-controlled endpoints at week 14 or 24 included ACR50, ACR70, at least a 75 % improvement in the Psoriasis Area Severity Index (PASI 75) and change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), enthesitis, dactylitis, van der Heijde Sharps (vdH-S) and Short Form (SF)-36 Physical Component (PC)/Mental Component (MC) scores. The study continued through 60 weeks (Janssen, 2017).

Go-ALIVE was a phase-III, multi-center, randomized, double-blind, placebo-controlled study which evaluated the efficacy and safety of Simponi Aria in adult patients (18 years of age and older) with active AS who had inadequate response or intolerance to NSAIDS.  Criteria included diagnosis of definite AS for at least 3 months according to modified New York criteria.  Patients had symptoms of active disease [Bath AS Disease Activity Index (BASDAI) greaterthan or equal to 4, VAS for total back pain of greater than or equal to 4, on scale of 0 to 10 cm (0 to 100 mm), and a hsCRP level of greater than or eual to 0.3 mg/dL (3 mg/L)].  Patients (n = 208) were randomized 1-to-1 to receive Simponi Aria 2 mg/kg (n = 105) as a 30-min IV infusion at weeks 0 and 4, and then every 8 weeks thereafter or placebo (n = 103) at weeks 0, 4 and 12, with cross-over to Simponi Aria at week 16.  The primary end-point was ASAS20 response at week 16.  Multiplicity-controlled end-points at week 16 included ASAS40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Bath Ankylosing Spondylitis Functional Index (BASFI), ASAS partial remission, Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis Quality of Life (ASQoL), and SF-36 PC/MC scores.  The study continued through 60 weeks (Janssen, 2017).

Intravenous Golimumab (Simponi Aria for Active Articular Juvenile Idiopathic Arthritis

In September 2020, the U.S. FDA approved Simponi Aria (golimumab) for patients 2 years of age and older for the treatment of active polyarticular juvenile idiopathic arthritis (pJIA) and extended the PsA indication for this same patient population. FDA approval was based on results from the GO-VIVA phase 3 clinical trial (NCT02277444), a multicenter, open-label, single-arm study in 127 children (age 2 to 17 yrs) with active pJIA who had active arthritis in five or more joints, despite receiving treatment with methotrexate for at least two months. The pJIA patient subtypes at study entry included rheumatoid factor negative (43%), rheumatoid factor positive (35%), enthesitis-related arthritis (9%), oligoarticular extended (6%), juvenile psoriatic arthritis (4%), and systemic JIA without systemic manifestations (3%). All patients received Simponi Aria 80 mg/m² as an intravenous infusion at Week 0, 4, and every 8 weeks through Week 52. Patients continued stable doses of MTX weekly through Week 28; after Week 28, changes in MTX dose were permitted. Efficacy was assessed as supportive endpoints through Week 52. The efficacy was generally consistent with responses in patients with RA. The efficacy of Simponi Aria in pediatric patients with pJIA was also based on the pharmacokinetic exposure and extrapolation of the established efficacy of Simponi Aria in RA patients (Janssen Biotech, 2020; Johnson & Johnson, 2020).

Intravenous Golimumab (Simponi Aria) for Rheumatoid Arthritis

The U.S. Food and Drug Administration (FDA) has approved an intravenous formulation of golimumab, Simponi Aria, for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) in combination with methotrexate. Simponi Aria (golimumab) is supplied as individually boxed‐single use vials as 50mg/4ml vial of IV injection. The Simponi Aria dose regimen is 2 mg/kg given as an intravenous infusion at weeks 0 and 4, then every 8 weeks thereafter. The infusion is given over a 30-minute period, providing a short infusion time for patients.

The approval is supported by findings from the Phase 3 Trial of Golimumab, an Anti-TNF-alpha Monoclonal Antibody, Administered Intravenously, in Subjects with Active Rheumatoid Arthritis Despite Methotrexate Therapy (GO-FURTHER) trial, a Phase 3, international multicenter, double-blind, placebo-controlled study including 592 adults with RA designed to compare ACR 20 response at week 14 in patients receiving an I.V. golimumab infusion plus methotrexate compared with patients receiving placebo infusions plus methotrexate. The trial included patients diagnosed with moderately to severely active RA who had at least six tender and six swollen joints at screening and baseline, had elevated CRP levels at screening and who had been receiving background methotrexate for at least 3 months. Patients were randomized 2:1 to receive a 30 (+/- 10) minute I.V. infusion of golimumab 2 mg/kg or placebo at weeks 0, 4, and then every 8 weeks; in both treatment arms, methotrexate was taken. The primary endpoint of the study was the proportion of subjects who had at least 20 percent improvement in American College of Rheumatology criteria (ACR 20) at week 14. At week 16, patients receiving placebo with less than 10 percent improvement in combined swollen and tender joint counts from baseline qualified for early escape and received I.V. golimumab 2 mg/kg infusions at week 16 and week 20 and every 8 weeks subsequent; patients receiving golimumab who qualified for early escape remained on their golimumab therapy. All patients receiving placebo crossed over to I.V. golimumab at week 24. Radiographs of the hands and feet were taken at baseline, week 24 (week 16 for early escape participants regardless of whether they had been randomized to placebo or golimumab) and week 52, and were scored using the van der Heijde-Sharp (vdH-S) score, an X-ray measure of joint destruction, including joint erosion and joint space narrowing in which higher scores indicate greater structural damage. 

Results from the trial revealed 59 percent (n = 231/395) of patients receiving treatment with I.V. golimumab plus methotrexate versus 25 percent of patients receiving placebo plus methotrexate (n = 49/197) (a difference with 95 percent CI 25.9, 41.4) experienced significant improvements in signs and symptoms at week 14, as demonstrated by at least 20 percent improvement in American College of Rheumatology criteria (ACR 20). A higher proportion of patients receiving I.V. golimumab plus methotrexate achieved at least a 50 percent improvement in ACR criteria (ACR 50) compared with patients receiving placebo plus methotrexate at week 14 (30 percent versus 9 percent, respectively, a difference with 95 percent CI 15.3, 27.2). Significant improvements in ACR 20 were observed as early as week 2, after a single I.V. golimumab infusion, as 33 percent of patients achieved an ACR 20 response versus 12 percent of patients receiving placebo. Radiographic progression of the hands and feet were assessed by the change from baseline in van der Heijde-Sharp (vdH-S) scores. At week 24, patients receiving I.V. golimumab plus methotrexate had a mean change in total vdH-S score of 0.03 from baseline, compared with a mean change of 1.09 in the placebo plus methotrexate group (P<0.001). At week 52, the mean change in total vdH-S score from baseline was 0.13 in I.V. golimumab treated patients versus 1.20 in placebo patients who crossed over to I.V. golimumab at either week 16 or 24. 

Through week 24, adverse events (AEs) occurred in 53 percent of patients receiving I.V. golimumab and 49 percent of patients receiving placebo, and serious AEs were reported in more I.V. golimumab-treated patients (4 percent) than placebo-treated patients (2 percent). In the controlled phase of the trial through Week 24, infections were observed in 27 percent of I.V. golimumab-treated patients compared with 24 percent of placebo-treated patients, and serious infections were observed in 0.9 percent of I.V. golimumab-treated patients and 0.0 percent of placebo-treated patients. One case of tuberculosis and one death, a myocardial infarction secondary to community-acquired pneumonia, were reported in the I.V. golimumab group. In addition, one death was reported among placebo-treated patients through week 24. Through week 24, the proportions of infusions with infusion reactions were 1.1 percent and 0.2 percent, respectively.

Other Indications

Asthma

In a randomized, double-blind, placebo-controlled study, Wenzel et al (2009) evaluated the safety and effectiveness of golimumab in a large population of patients with uncontrolled, severe persistent asthma.  A total of 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through week 52.  Co-primary endpoints were the change from baseline through week 24 in pre-bronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through week 24.  No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95 % confidence interval (CI): -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696 to 5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 versus combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24.  Through week 24, 2.6 % of patients treated with placebo versus 19.5 % of those treated with golimumab discontinued the study agent, and 1.3 % and 7.8 % discontinued study participation, respectively.  An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the week-24 database lock.  Through week 76, 20.5 % of patients treated with placebo and 30.3 % of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients.  One death and all 8 malignancies occurred in the active groups.  The authors concluded that overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma.

Crohn's Disease

An UpToDate review on "Overview of medical management of high-risk, adult patients with moderate to severe Crohn disease" (Hashash and Regueiro, 2020) do not provide a recommendation for golimumab for treatment of moderate to severe Crohn's disease in adult patients. 

Yang and colleagues (2020) noted that biologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates.  After multiple failed therapies, combining 2 biologic therapies is possibly the sole medical alternative to recurrent surgery.  However, data on this approach are limited.  These researchers examined the safety and efficacy of concomitant use of 2 biologic therapies in the largest cohort to-date of refractory Crohn's disease patients.  Data were extracted from Crohn's disease patients started on dual biologic therapy at 2 referral centers.  Biologics used include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab.  The primary outcome was endoscopic improvement (greater than 50 % reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated).  Endoscopic remission (SES-CD less than 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 of less than 8), and CRP were also assessed.  A total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified.  The majority of patients had prior surgical resections (91 %), stricturing (59 %) or penetrating (36 %) phenotype, and peri-anal fistulas (50 %).  Median number of prior failed biologics was 4.  Endoscopic improvement occurred in 43 % of trials and 26 % achieved endoscopic remission; 50 % had clinical response and 41 % achieved clinical remission.  There were significant post-treatment reductions in median SES-CD (14.0 [12.0 to 17.5] to 6.0 [2.5 to 8.0], p = 0.0005], PRO-2 (24.1 [20.3 to 27.0] to 13.4 [4.6 to 21.8], p = 0.002] and CRP (17.0 [11.0 to 24.0] to 9.0 [4.0 to 14.0], p = 0.02).  Presence of peri-anal fistulas decreased from 50 % to 33 %; AEs occurred in 13 % of trials.  The authors concluded that dual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics.  Moreover, these researchers stated that further studies are needed to validate this approach.

Sarcoidosis

Bargagli et al (2011) noted that sarcoidosis is a granulomatous lung disease in which several cytokines play a pivotal pathogenetic role.  Steroid-resistant disease can be treated with immunosuppressive drugs, anti-malarial therapies and recently with anti-TNF-alpha agents.  The use of biological agents for the treatment of sarcoidosis springs from research into the pathogenesis of the disease and also from the experience of rheumatologists with other chronic inflammatory diseases.  Rituximab, golimumab and ustekinumab are cytokine modulators, useful in the treatment of immuno-inflammatory disorders, for which randomized trials to evaluate safety and efficacy in sarcoidosis are not yet available.  Novel anti-cytokine drugs administered alone or in association may offer a new approach to treatment of the disease.

Judson et al (2014) noted that sarcoidosis is characterized by non-caseating granulomas that secrete pro-inflammatory cytokines, including interleukin (IL)-12, IL-23, and TNF-alpha.  Ustekinumab and golimumab are monoclonal antibodies that specifically inhibit IL-12/IL-23 and TNF-α, respectively.  These researchers examined the safety and effectiveness of ustekinumab or golimumab in patients with chronic sarcoidosis.  Patients with chronic pulmonary sarcoidosis (lung group) and/or skin sarcoidosis (skin group) received either 180 mg ustekinumab at week 0 followed by 90 mg every 8 weeks, 200 mg golimumab at week 0 followed by 100 mg every 4 weeks, or placebo.  Patients underwent corticosteroid tapering between weeks 16 and 28.  The primary end-point was week 16 change in percentage predicted forced vital capacity (ΔFVC % pred) in the lung group.  Major secondary end-points were: week 28 for ΔFVC % pred, 6-min walking distance, St George's Respiratory Questionnaire (lung group), and Skin Physician Global Assessment response (skin group).  At week 16, no significant differences were observed in ΔFVC % pred with ustekinumab (-0.15, p = 0.13) or golimumab (1.15, p = 0.54) compared with placebo (2.02).  At week 28, there were no significant improvements in the major secondary end-points, although a non-significant numerically greater Skin Physician Global Assessment response was observed following golimumab treatment (53 %) when compared with the placebo (30 %).  Serious adverse events were similar in all treatment groups.  The authors concluded that although treatment was well-tolerated, neither ustekinumab nor golimumab demonstrated effectiveness in pulmonary sarcoidosis.  However, trends towards improvement were observed with golimumab in some dermatological end-points.

Uveitis

In a non-randomized, retrospective, multi-centered, interventional case-series study, Cordero-Coma et al (2014) evaluated the short-term safety and effectiveness of GLM for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy.  A total of 13 patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressants were included in this study.  All included patients were treated with GLM (50 mg every 4 weeks) during at least 6 months.  Clinical evaluation and treatment-related side effects were assessed at least 4 times in all included patients.  Eight men and 5 women (22 affected eyes) with a median age of 30 years (range of 20 to 38) and active immune-mediated uveitides were studied.  Golimumab was used in combination with conventional immunosuppressants in 7 patients (53.8 %).  Golimumab therapy achieved complete control of inflammation in 12/13 patients (92.3 %) after 6 months of treatment.  There was a statistically significant improvement in mean best corrected visual acuity (BCVA) (0.60 versus 0.68, p = 0.009) and mean 1 mm central retinal thickness (317 versus 261.2 μ, p = 0.05) at the 6-month endpoint when compared to basal values.  No major systemic adverse effects associated with GLM therapy were observed.  The authors concluded that GLM is a new and promising therapeutic option for patients with severe and refractory uveitis.

In a retrospective study, Miserocchi et al (2014) evaluated the long-term effectiveness of GLM in patients with severe recalcitrant uveitis who had inadequate response to previous biologics.  A total of 13 patients with juvenile idiopathic arthritis, 4 with HLA-B27-associated uveitis were included in this study.  Indication for treatment was active uveitis despite biologics; GLM dosing was 50 mg monthly/subcutaneously.  Main outcome measures included uveitis activity, visual acuity improvement, decrease in systemic therapy (corticosteroids/immunosuppressants), and adverse events.  Of 17 patients (34 affected eyes), response to GLM was seen in 14 patients; at last visit uveitis was inactive in 12 patients.  Three patients were non-responders.  Mean follow-up time on GLM was 21.9 months.  Visual acuity remained stable in 26 eyes, improved in 7, and worsened in 1.  Mean systemic prednisolone dose before and after GLM was 12.5 to 3.5 mg/day.  One patient developed pulmonary infection.  The authors concluded that GLM may be a promising new therapeutic option for severe uveitis patients who have not responded to other biologics.

Sanchez-Cano et al (2013) noted that TNF-alpha plays a central role in both the inflammatory response and that of the immune system.  Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis.  Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents.  These investigators reviewed these off-label uses of anti-TNF blockers in 3 common conditions:

1. Behçet's disease,
2. sarcoidosis, and
3. non-infectious uveitis. 

Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review was mainly based on case reports and case series.

Furthermore, an expert panel’s recommendations for the use of anti-TNF biologic agents in patients with ocular inflammatory disorders including Behcet's disease, panuveitis, posterior uveitis, and scleritis (Levy-Clarke et al, 2014) does not mention golimumab as a therapeutic option.

Appendix

Appendix A: Examples of Contraindications to Methotrexate

1. Clinical diagnosis of alcohol use disorder, alcoholic liver disease or other chronic liver disease  
2. Breastfeeding
3. Blood dyscrasias (e.g., thrombocytopenia, leukopenia, significant anemia)
4. Elevated liver transaminases
5. History of intolerance or adverse event
6. Hypersensitivity
7. Interstitial pneumonitis or clinically significant pulmonary fibrosis
8. Myelodysplasia
9. Pregnancy or currently planning pregnancy
10. Renal impairment
11. Significant drug interaction

Appendix B: Examples of Contraindications to the Use of NSAIDs

1. Allergic-type reaction following aspirin or other NSAID administration
2. Asthma
3. Gastrointestinal bleeding
4. History of intolerance or adverse event
5. Significant drug interaction
6. Urticaria

Appendix C: Risk factors for Articular Juvenile Idiopathic Arthritis

1. Positive rheumatoid factor
2. Positive anti-cyclic citrullinated peptide antibodies
3. Pre-existing joint damage

Appendix D: Examples of Conventional Therapy Options for UC

1. Mild to moderate disease – induction of remission:

   1. Oral mesalamine (e.g., Asacol, Asacol HD, Lialda, Pentasa), balsalazide, olsalazine
   2. Rectal mesalamine (e.g., Canasa, Rowasa)
   3. Rectal hydrocortisone (e.g., Colocort, Cortifoam)
   4. Alternatives: prednisone, azathioprine, mercaptopurine, sulfasalazine

2. Mild to moderate disease – maintenance of remission:

   1. Oral mesalamine, balsalazide, olsalazine, rectal mesalamine
   2. Alternatives: azathioprine, mercaptopurine, sulfasalazine

3. Severe disease – induction of remission:

   1. Prednisone, hydrocortisone IV, methylprednisolone IV 
   2. Alternatives: cyclosporine IV, tacrolimus, sulfasalazine

4. Severe disease – maintenance of remission:

   1. Azathioprine, mercaptopurine 
   2. Alternative: sulfasalazine

Appendix E: Brands of Targeted Immune Modulators and FDA-approved Indications

Table: Brands of Targeted Immune Modulators and FDA-approved Indications:

Brand Name	Generic Name	FDA Labeled Indications
Actemra	tocilizumab	Cytokine release syndrome (CRS) Giant cell arteritis Juvenile idiopathic arthritis Rheumatoid arthritis Systemic juvenile idiopathic arthritis Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
Arcalyst	rilonacept	Cryopyrin-associated periodic syndromes Deficiency of interleukin-1 receptor antagonist (DIRA)
Avsola	infliximab-axxq	Ankylosing spondylitis Crohn's disease Psoriatic arthritis Plaque psoriasis Rheumatoid arthritis Ulcerative colitis
Cimzia	certolizumab	Ankylosing spondylitis or axial spondyloarthritis Crohn's disease Plaque psoriasis Psoriatic arthritis Rheumatoid arthritis
Cosentyx	secukinumab	Ankylosing spondylitis or axial spondyloarthritis Plaque psoriasis Psoriatic arthritis
Enbrel	etanercept	Ankylosing spondylitis Juvenile idiopathic arthritis Plaque psoriasis Psoriatic arthritis Rheumatoid arthritis
Entyvio	vedolizumab	Crohn's disease Ulcerative colitis
Humira	adalimumab	Ankylosing spondylitis Crohn's disease Hidradenitis suppurativa Juvenile idiopathic arthritis Plaque psoriasis Psoriatic arthritis Rheumatoid arthritis Ulcerative colitis Uveitis
Ilaris	canakinumab	Adult-onset Still's disease Periodic fever syndromes Systemic juvenile idiopathic arthritis
Ilumya	tildrakizumab-asmn	Plaque psoriasis
Inflectra	infliximab	Ankylosing spondylitis Crohn's disease Psoriatic arthritis Plaque psoriasis Rheumatoid arthritis Ulcerative colitis
Kevzara	sarilumab	Rheumatoid arthritis
Kineret	anakinra	Cryopyrin-associated periodic syndromes Deficiency of interleukin-1 receptor antagonist (DIRA) Rheumatoid arthritis
Olumiant	baricitinib	Rheumatoid arthritis
Orencia	abatacept	Juvenile idiopathic arthritis Psoriatic arthritis Rheumatoid arthritis
Otezla	apremilast	Oral ulcers associated with Behçet’s Disease Plaque psoriasis Psoriatic arthritis
Remicade	infliximab	Ankylosing spondylitis Crohn's disease Psoriatic arthritis Plaque psoriasis Rheumatoid arthritis Ulcerative colitis
Rinvoq	upadacitinib	Rheumatoid arthritis
Rituxan	rituximab	Chronic lymphocytic leukemia Granulomatosis with polyangiitis Microscopic polyangiitis Pemphigus vulgaris Rheumatoid arthritis Various subtypes of non-Hodgkin's lymphoma
Siliq	brodalumab	Plaque psoriasis
Simponi	golimumab	Ankylosing spondylitis Psoriatic arthritis Rheumatoid arthritis Ulcerative colitis
Simponi Aria	golimumab intravenous	Ankylosing spondylitis Juvenile idiopathic arthritis Psoriatic arthritis Rheumatoid arthritis
Skyrizi	risankizumab-rzaa	Plaque psoriasis
Stelara	ustekinumab	Crohn's disease Plaque psoriasis Psoriatic arthritis Ulcerative colitis
Taltz	ixekinumab	Ankylosing spondylitis or axial spondyloarthritis Plaque psoriasis Psoriatic arthritis
Tremfya	guselkumab	Plaque psoriasis Psoriatic arthritis
Tysabri	natalizumab	Crohn's disease Multiple sclerosis
Xeljanz	tofacitinib	Rheumatoid arthritis Psoriatic arthritis Ulcerative Colitis
Xeljanz XR	tofacitinib, extended release	Rheumatoid arthritis Psoriatic arthritis Ulcerative colitis

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
Other CPT codes related to the CPB:
71045 - 71048	Radiologic examination, chest
85651	Sedimentation rate, erythrocyte; non-automated
85652	Sedimentation rate, erythrocyte; automated
86140	C-reactive protein
86141	C-reactive protein; high sensitivity (hsCRP)
86200	Cyclic citrullinated peptide (CCP), antibody
86430	Rheumatoid factor; qualitative
86431	Rheumatoid factor; quantitative
86480	Tuberculosis test, cell mediated immunity antigen response measurement; gamma interferon
86481	Tuberculosis test, cell mediated immunity antigen response measurement; enumeration of gamma interferon - producing T cells in cell suspension
86580	Skin test; tuberculosis, intradermal
96365 - 96368	Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug)
96369 - 96371	Subcutaneous infusion for therapy or prophylaxis (specify substance or drug)
96372	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
96374	Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); intravenous push, single or initial substance/drug
96379	Unlisted therapeutic, prophylactic, or diagnostic intravenous or intra-arterial injection or infusion
HCPCS codes covered if selection criteria are met:
There is no specific code for subcutaneously administered golimumab (Simponi) :
J1602	Injection, golimumab, 1 mg, for intravenous use [Simponi Aria only]
Other HCPCS codes related to the CPB:
J0129	Injection, abatacept, 10 mg
J0135	Injection, adalimumab, 20 mg
J0717	Injection, certolizumab pegol, 1 mg
J1020	Injection, methylprednisolone acetate, 20 mg
J1030	Injection, methylprednisolone acetate, 40 mg
J1040	Injection, methylprednisolone acetate, 80 mg
J1094	Injection, dexamethasone acetate, 1 mg
J1130	Injection, diclofenac sodium, 0.5 mg
J1438	Injection, etanercept, 25 mg
J1600	Injection, gold sodium thiomalate, up to 50 mg
J1745	Injection infliximab, 10 mg
J2920	Injection, methylprednisolone sodium succinate, up to 40 mg [Solu-Medrol]
J2930	Injection, methylprednisolone sodium succinate, up to 125 mg [Solu-Medrol]
J3245	Injection, tildrakizumab, 1 mg
J3262	Injection, tocilizumab, 1 mg
J7500	Azathioprine, oral, 50 mg
J7501	Azathioprine, parenteral, 100 mg
J7502	Cyclosporine, oral, 100 mg
J7509	Methylprednisolone, oral, per 4 mg
J7510	Prednisolone, oral, per 5 mg
J7512	Prednisone, immediate release or delayed release, oral, 1 mg
J7515	Cyclosporine, oral, 25 mg
J7516	Cyclosporine, parenteral, 250 mg
J8530	Cyclophosphamide, oral, 25 mg
J8540	Dexamethasone, oral, 0. 25 mg
J8610	Methotrexate, oral, 2.5 mg
J9070	Cyclophosphamide, 100 mg
J9250	Methotrexate sodium, 5 mg
J9260	Methotrexate sodium, 50 mg
J9312	Injection, rituximab, 10 mg
Q5109	Injection, infliximab-qbtx, biosimilar, (ixifi), 10 mg
S0108	Mercaptopurine, oral, 50 mg
ICD-10 codes covered if selection criteria are met for I.V. golimumab (Simponi Aria) :
M05.00 - M06.9 M08.00 - M08.99	Rheumatoid arthritis
M45.0 - M45.AB	Ankylosing spondylitis
ICD-10 codes not covered for indications listed in the CPB (not all inclusive):
H20.00 - H21.29	Disorders of iris and ciliary body [ocular inflammatory disorders]
K50.00 - K50.919	Crohn's disease [regional enteritis]
ICD-10 codes covered if selection criteria are met for subcutaneously administered golimumab (Simponi) :
K51.00 - K51.919	Ulcerative colitis
L40.50 - L40.59	Arthropathic psoriasis [see CPB 658 Psoriasis: Biological Therapies]
M05.00 - M06.9 M08.00 - M08.99	Rheumatoid arthritis
M08.1	Juvenile ankylosing spondylitis
M45.0 - M45.AB	Ankylosing spondylitis
ICD-10 codes not covered for indications listed in the CPB (not all inclusive):
D86.0	Sarcoidosis of lung
H20.00 - H21.29	Disorders of iris and ciliary body [ocular inflammatory disorders]
J45.20 - J45.998	Asthma
K50.00 - K50.919	Crohn's disease [regional enteritis]

The above policy is based on the following references: