Abatacept (Orencia)

Number: 0720

  1. Aetna considers abatacept (Orencia) 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) within 6 months of initiating therapy for persons who are naiive to biologics, and repeated yearly for members with risk factors* for TB that are continuing therapy with biologics:

    1. Treatment of adult members 18 years of age or older with moderately to severely active rheumatoid arthritis (see Note); or

    2. Treatment of persons aged 6 years and older with moderate or severely active polyarticular juvenile rheumatoid arthritis (juvenile idiopathic arthritis) (see Note).

  2. Note: There are several brands of targeted immune modulators on the market.  There is a lack of reliable evidence that any one brand of targeted immune modulator is superior to other brands for medically necessary indications.  Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), Simponi Aria (golimumab intravenous), and Stelara (ustekinumab) brands of targeted immune modulators ("least cost brands of targeted immune modulators") are less costly to Aetna.  Consequently, because other brands (e.g., Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), Entyvio (vedolizumab), Kineret (anakinra), Orencia (abatacept), Otezla (apremilast), Rituxan (rituximab), Simponi (golimumab) and Xeljanz (tofacitinib)) of targeted immune modulators are more costly than these least cost brands of targeted immune modulators, and least cost brands of targeted immune modulators are at least as likely to produce equivalent therapeutic results, no other brands of targeted immune modulator will be considered medically necessary unless the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulator: Enbrel, Humira, Remicade, Simponi Aria, or Stelara, for the same medically necessary indication. If the least costly targeted immune modulator does not have the labeled indication (see appendix), then Aetna considers medically necessary another brand of targeted immune modulator that has the required labeling indication. For some Aetna plans, the use of other brands of intravenously infused targeted immune modulators (toclizumab (Actemra), abatacept (Orencia), and rituximab (Rituxan)) will not be considered medically necessary unless the member has a contraindication, intolerance or incomplete response to the least cost brand of intravenously infused targeted immune modulator, infliximab (Remicade) for the same medically necessary indication.

  3. Aetna considers abatacept experimental and investigational for the treatment of the following indications (not an all-inclusive list) because its effectiveness for these conditions has not been established:

    1. Ankylosing spondylitis
    2. Common variable immunodeficiency
    3. Crohn's disease
    4. Focal segmental glomerulosclerosis
    5. Graft versus host disease
    6. Juvenile dermatomyositis
    7. Lupus nephritis
    8. Multiple sclerosis
    9. Polyarthritis/spondyloarthritis
    10. Proteinuric kidney disease
    11. Psoriasis
    12. Psoriatic arthritis
    13. Reiter's syndrome
    14. Relapsing polychondritis
    15. Sjogren's syndrome
    16. Systemic lupus erythematosus
    17. Systemic sclerosis
    18. Systemic vasculitis
    19. Takayasu's arteritis
    20. Type 1 diabetes
    21. Ulcerative colitis
    22. Uveitis associated with Behcet's disease
    23. Wegeners granulomatosis.

* Risk factors for TB include: persons with close contact to people with infectious TB disease; persons who have recently emigrated from areas of the world with high rates of TB (e.g., Africa, Asia, Eastern Europe, Latin America, and Russia); children less than 5 years of age who have a positive TB test; groups with high rates of TB transmission (e.g., homeless persons, injection drug users, and persons with HIV infection); persons who work or reside with people who are at an increased risk for active TB (e.g., hospitals, long-term care facilities, correctional facilities, and homeless shelters) (CDC, 2012).

See also: CPB 0314 - Rituximab (Rituxan)CPB 0315 - Enbrel (Etanercept)CPB 0341 - Remicade (infliximab)CPB 0595 - Kineret (Anakinra); and CPB0 0655 - Adalimumab (Humira).


Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder characterized by inflammation of synovial joints resulting in progressive erosion of cartilage and bone.  The main objectives of treatment of RA are three-fold: to interfere with the disease process (i.e., inflammation and destruction of the joints), preserve physical function, and prevent long-term disability.  The American College of Rheumatology (ACR)’s guidelines for the treatment of RA (1996) recommend that newly diagnosed patients with RA begin treatment with disease-modifying anti-rheumatic drugs (DMARDs) within 3 months of diagnosis.  Methotrexate remains the most commonly prescribed DMARD and is the standard by which recent new and emerging therapies are measured.

In addition to traditional DMARDs, tumor necrosis factor (TNF) antagonists (e.g., adalimumab, etanercept, infliximab, and golimumab) are currently being used for the treatment of RA.  However, only 60 to 70 % of RA patients respond to treatment with a TNF antagonist.  Furthermore, the majority of patients show only a partial response according to ACR20 (20 % improvement) criteria (Voll and Kalden, 2005).  Contraindications such as infection and cardiac failure also add to the number of patients who need alternative treatment.

A better understanding of the inflammatory pathway in RA has led to the development of a number of targeted biological therapies.  One of these targeted biological agents is abatacept, a novel fusion protein designed to modulate the T cell co-stimulatory signal mediated through the CD28-CD80/86 pathway.  It inhibits T-cell activation and interrupts the process leading to inflammation in RA (Pollard and Choy, 2005; Ruderman and Pope, 2005).

Published clinical studies have found that patients with severe RA who received abatacept with at least one other DMARD showed statistically significant improvement in tender, swollen joints and other clinical measures compared with placebo.  However, abatacept should not be administered in conjunction with other biological agents because of reported increased rates of serious adverse events, including serious infections.

In a 12-month, multi-center, randomized, double-blind, placebo-controlled phase 2 clinical trial, Kremer and colleagues (2005) ascertained the safety and effectiveness of abatacept in patients with RA that has remained active despite methotrexate therapy.  A total of 339 patients were randomly assigned to one of the 3 groups: (i) 10 mg/kg abatacept (n = 115), (ii) 2 mg/kg abatacept (n = 105), or placebo (n = 119).  A significantly greater percentage of patients treated with 10 mg/kg abatacept met the ACR20 response criteria at 1 year compared with patients who received placebo (62.6 % versus 36.1 %; p < 0.001).  Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7 % versus 20.2 %; p < 0.001) and ACR70 responses (20.9 % versus 7.6 %; p = 0.003) compared with patients who received placebo.  For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire (HAQ) scores compared with those who received placebo (49.6 % versus 27.7 %; p < 0.001).  Abatacept at a dosage of 10 mg/kg resulted in an increase in rates of remission (Disease Activity Score in 28 joints of less than 2.6) compared with placebo at 1 year (34.8 % versus 10.1 %; p < 0.001).  The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.  These researchers concluded that abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite methotrexate treatment.  Abatacept was found to be well tolerated and safe over the course of 1 year.

In a randomized, double-blind, phase 3 clinical trial (n = 322), Genovese and colleagues (2005)  assessed the safety and effectiveness of abatacept in patients with active RA and an inadequate response to at least 3 months of anti-TNF-alpha therapy.  Patients were randomly assigned in a 2:1 ratio to receive abatacept (n = 223) or placebo (n = 99) on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one DMARD.  Patients stopped anti-TNF-alpha therapy before randomization.  The rates of ACR20 responses and improvement in functional disability, as reflected by scores for the HAQ disability index, were evaluated.  After 6 months, the rates of ACR20 responses were 50.4 % in the abatacept group and 19.5 % in the placebo group (p < 0.001); the respective rates of ACR50 and ACR70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 % versus 3.8 %, p < 0.001; and 10.2 % versus 1.5 %, p = 0.003).  At 6 months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as indexed by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 % versus 23.3 %, p < 0.001).  The incidence of adverse reactions as well as peri-infusional adverse events was 79.5 % and 5.0 %, respectively, in the abatacept group and 71.4 % and 3.0 %, respectively, in the placebo group.  The incidence of serious infections was 2.3 % in each group.  These investigators concluded that abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.

Schiff et al (2006) reported on the results of a randomized multi-center clinical trial comparing abatacept (n = 156) to infliximab (n = 165) and placebo (n = 110) in adults with moderate to severe RA an inadequate response to methotrexate and no previous treatment with a TNF antagonist.  At the end of 6 months, the mean reduction in Disease Activity Score-28 using Erythrocyte Sedimentation Rate (DAS28 [ESR]) from baseline was - 1.48 for placebo, -2.53 for abatacept (p < 0.001 versus placebo), and -2.25 for infliximab (p < 0.001 versus placebo).  After 12 months, the change in DAS28[ESR] from baseline was -2.88 for abatacept and -2.25 for infliximab.  (The placebo group was placed on abatacept after 6 months and not included in the 12 month analysis).  The investigators found that abatacept was associated with fewer serious infections or discontinuations due to adverse events than infliximab.  The rate of serious adverse events after six months was 5.1 % for abatacept, 11.8 % for placebo and 11.5 % for infliximab).  The rate of discontinuation due to adverse events was 1.9 % for abatacept, 0.9 % for placebo, and 4.8 % for infliximab.  At 12 months, the rate of serious adverse events was 9.6 % for abatacept and 18.2 % for infliximab.  The rate of discontinuation due to adverse events at 12 months was 3.2 % for abatacept and 7.3 % for infliximab.

The United States Food and Drug Administration (FDA) initially approved abatacept (Orencia) for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA who have had an inadequate response to one or more DMARDs such as methotrexate or a TNF antagonist.  Combinational therapy with abatacept and a targeted biological agent is not recommended.  In clinical trials, patients receiving concomitant abatacept and TNF antagonist therapy experienced more infections (63 %) and serious infections (4.4 %) compared to patients treated with only TNF antagonists (43 % and 0.8 %, respectively), without an important improvement in effectiveness.  The most common side effects associated with the use of abatacept were dizziness, headache, hypertension, upper respiratory tract infection, nasopharyngitis, and nausea. Although the requirement for a trial of DMARDs was subsequently removed from the FDA labeling, an assessment of abatacept for rheumatoid arthritis by the National Institute for Health and Clinical Excellence (NICE, 2008) outlined the uncertainties regarding the comparative effectiveness of abatacept to DMARDs and tumor necrosis factor inhibitors.

Abatacept has been approved by the FDA for use in reducing signs and symptoms of moderately to severely active polyarticular juvenile RA (juvenile idiopathic arthritis) in pediatric patients 6 years and older.  The approval was based on data from the AWAKEN study (Abatacept Withdrawal study to Assess efficacy and safety in Key Endpoints in juvenile idiopathic arthritis Not responding to current treatment), a 3-part study including an open-label extension in children with polyarticular juvenile RA.  Overall, the 3-part trial showed that abatacept therapy yielded improvements across 3 major subtypes of juvenile RA through 1 year in patients aged 6 to 17 years whose disorder had not responded to 1 or more DMARDs, such as methotrexate or tumor necrosis factor (TNF) antagonists.  Patients had a disease duration of approximately 4 years with moderately to severely active disease at study entry, as determined by baseline counts of active joints (mean of 16) and joints with loss of motion (mean of 16); patients had elevated C-reactive protein (CRP) levels (mean of 3.2 mg/dL) and ESR (mean of 32 mm/h).

In the first part of the study, 190 patients received 16 weeks of intravenous abatacept on days 1, 15, and 29, and every month thereafter.  Efficacy was assessed with the Rheumatology Pediatric American College of Rheumatology (ACR Pedi) 30 response, defined as a 30 % or greater improvement in at least 3 of the 6 ACR Pedi response variables and no more than 1 indicator worsening by 30 % or more.  Results at 4 months showed that ACR Pedi 30 responses were consistent across all juvenile RA subtypes, including oligoarticular extended (59.3 %), polyarticular rheumatoid factor-positive (68.4 %), polyarticular rheumatoid factor-negative (64.3 %), and systemic juvenile RA with polyarticular course (64.9 %).  Children who were new to biologic therapy appeared to have higher rates of ACR 30, 50, 70, and 90 versus those in whom previous biologic treatments had failed (76 % versus 38.6 %; 60 % versus 24.6 %; 36 % versus 10.5 %; and 17 % versus 1.8 %, respectively).

Patients with an ACR Pedi 30 response in the first part of the study ( n = 122) were then randomized in the second part of the study to receive abatacept or placebo for an additional 24 weeks or until disease flare.  A flare was defined as a 30 % or greater worsening in at least 3 of the 6 ACR Pedi response variables, a minimum of 2 active joints, and no more than 1 indicator improving by 30 %.  Data from the second phase of the study showed that continued abatacept therapy significantly reduced the incidence of disease flare vs placebo (20 % versus 53 %; p < 0.001; hazard ratio, 0.31; 95 % CI: 0.16 to 0.59).

Furthermore, abatacept-treated children were significantly more likely to show ACR responses of 30, 50, and 70, which were maintained for up to 1 year in the open-label study extension (third phase of AWAKEN).

The investigators reported that, in general, adverse reactions in pediatric patients were similar in type and frequency to those observed in adult studies.  The overall frequency of adverse events during the first part of the study was 70 %; infections (36 %) most commonly involved the upper respiratory tract and nasopharyngitis and were consistent with those observed in outpatient pediatric populations.  Other events that occurred in 5 % or more of patients were headache, nausea, diarrhea, cough, pyrexia, and abdominal pain.

According to the FDA-approved labeling, abatacept may be used alone or with methotrexate for juvenile rheumatoid arthritis.  The labeling states that abatacept should not be administered concomitantly with TNF antagonists, and that abatacept is not recommended for use concomitantly with other biologic rheumatoid arthritis therapy, such as anakinra.  The recommended dose of abatacept for patients 6 to 17 years of age with juvenile RA who weigh less than 75 kg is 10 mg/kg calculated based on the patient’s body weight at each administration.  Pediatric patients weighing 75 kg or more should be administered abatacept following the adult dosing regimen, not to exceed a maximum dose of 1,000 mg.  Following the initial administration, abatacept should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.  Although the FDA-approved labeling does not limit use of abatacept to persons with juvenile RA that have failed DMARDs, clinical studies submitted to the FDA have focused on JRA patients who have failed DMARDS.

A systematic evidence review of targeted immunomodulators by the Drug Effectiveness Review Project (DERP) (Thaler, et al., 2012) found one fair-quality, double-blinded head-to head trial provided evidence of moderate strength that abatacept and infliximab do not differ in efficacy for the treatment of rheumatoid arthritis up to 6 months. The safety profile, however, appeared to be better for abatacept than for infliximab with fewer serious adverse events (9.6% compared with 18.2%) and fewer serious infections (1.9% compared with 8.5%). The review found that other direct comparisons of targeted immune modulators for the treatment of rheumatoid arthritis were limited to one small randomized controlled trial and multiple observational studies rendering evidence of low strength. The review stated that adjusted indirect comparisons suggested greater efficacy for etanercept than abatacept, adalimumab, anakinra, and infliximab for the treatment of rheumatoid arthritis.

The DERP review (Thaler, et al., 2012) found no  head-to-head trials comparing the efficacy and safety of targeted immune modulators for the treatment juvenile idiopathic arthritis. The review stated that the general efficacy of abatacept, adalimumab, etanercept, infliximab, and tocilizumab for the treatment of juvenile idiopathic arthritis is supported by one randomized controlled trial for each drug. The review noted, however, that sample sizes of these studies were small and active run-in periods limited the applicability of results. In efficacy trials statistically significantly fewer patients on targeted immune modulators (20% to 37%) experienced disease flares than children treated with placebo (53% to 83%).

Blockade of antigen non-specific co-stimulatory signals is also being investigated for the treatment of autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus (Dumont, 2004; Davidson et al, 2005).  However, there is currently insufficient evidence that abatacept is effective in treating patients with autoimmune diseases.

Ong and Denton (2010) reviewed the evidence and recent developments leading to novel therapeutics in scleroderma.  Recent advances have been made in understanding the key pathogenetic aspects of scleroderma, and these have led to potential targeted therapeutic agents for the management of these patients.  Preliminary data from early clinical trials suggested that tyrosine kinase molecules may be potential candidates for therapy, especially in the fibrotic phase of the disease.  On the basis of the new insights into the key role of effector T cells, in particular Th-17 and T regulatory subsets, T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial.  By analogy, recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important in the pathogenesis of the disease.  3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, endothelin receptor antagonists and phosphodiesterase type V inhibitor have been shown to be useful to treat the vascular manifestations associated with systemic sclerosis.  Hematopoietic stem cell transplantation following immune ablation holds considerable promise in resetting of the immune system, and trial results are awaited.  The authors concluded that although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair.  These recent findings will need to be confirmed by larger, multi-center, randomized controlled trials.

In a randomized, double-blind, placebo-controlled trial, Orban et al (2011) evaluated the effect of abatacept in recent-onset type 1 diabetes.  Patients aged 6 to 45 years recently diagnosed with type 1 diabetes were randomly assigned (2:1) to receive abatacept (10 mg/kg, maximum 1,000 mg per dose) or placebo infusions intravenously on days 1, 14, 28, and monthly for a total of 27 infusions over 2 years.  Computer-generated permuted block randomization was used, with a block size of 3 and stratified by participating site.  Neither patients nor research personnel were aware of treatment assignments.  The primary outcome was baseline-adjusted geometric mean 2-hr area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years' follow-up.  Analysis was by intention-to-treat for all patients for whom data were available.  A total of 112 patients were assigned to treatment groups (35 placebo, 77 abatacept).  Adjusted C-peptide AUC was 59 % (95 % CI: 6.1 to 112) higher at 2 years with abatacept (n = 73, 0·378 nmol/L) than with placebo (n = 30, 0·238 nmol/L; p = 0·0029).  The difference between groups was present throughout the trial, with an estimated 9.6 months' delay (9 5% CI: 3.47 to 15.6) in C-peptide reduction with abatacept.  There were few infusion-related adverse events (36 reactions occurred in 17 [22 %] patients on abatacept and 11 reactions in 6 [17 %] on placebo).  There was no increase in infections (32 [42 %] patients on abatacept versus 15 [43 %] on placebo) or neutropenia (7 [9 %] versus 5 [14 %]).  The authors concluded that co-stimulation modulation with abatacept slowed reduction in β-cell function over 2 years.  The beneficial effect suggested that T-cell activation still occurs around the time of clinical diagnosis of type 1 diabetes.  Yet, despite continued administration of abatacept over 24 months, the decrease in β-cell function with abatacept was parallel to that with placebo after 6 months of treatment, causing these researchers to speculate that T-cell activation lessens with time.  They stated that further observation is needed to establish whether the beneficial effect continues after cessation of abatacept infusions.

In a prospective, open-label, pilot study, Song et al (2011) examined the short-term safety and effectiveness of abatacept in patients with ankylosing spondylitis (AS).  Abatacept (10 mg/kg) was administered intravenously on days 1, 15, 29 and every 28 days thereafter up to week 24 in 15 TNFα-inhibitor naive patients (group 1) and 15 patients with inadequate response to TNFα inhibitors (group 2) with active AS.  The primary end point was the proportion of patients with 40 % improvement according to the Assessment of SpondyloArthritis international Society criteria (ASAS40) in both groups at week 24.  At week 24, ASAS40 was reached by 13 % of group 1 and 0 % of group 2; 20 % improvement (ASAS20) was reached by 27 % and 20 %, respectively.  There was no significant change of Bath Ankylosing Spondylitis Disease Activity Index score, patient global assessment or C reactive protein.  Overall, abatacept was well-tolerated.  The authors concluded that in this pilot open-label AS study a major response was not observed.

Sandborn et al (2012) evaluated the safety and effectiveness of abatacept as induction (IP) and maintenance (MP) therapy in adults with active, moderate-to-severe Crohn's disease (CD) (CD-IP; CD-MP) and ulcerative colitis (UC) (UC-IP1; UC-MP).  In CD-IP and UC-IP1, 451 patients with CD and 490 patients with UC were randomized to abatacept 30, 10, or 3 mg/kg (according to body weight) or placebo, and dosed at weeks 0, 2, 4, and 8.  In MP, 90 patients with CD and 131 patients with UC who responded to abatacept at week 12 in the induction trials were randomized to abatacept 10 mg/kg or placebo every 4 weeks through week 52.  In CD-IP, 17.2 %, 10.2 %, and 15.5 % of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at weeks 8 and 12, versus 14.4 % receiving placebo (p = 0.611, p = 0.311, and p = 0.812, respectively).  In UC-IP1, 21.4 %, 19.0 %, and 20.3 % of patients receiving abatacept 30, 10, and 3 mg/kg achieved a clinical response at week 12, versus 29.5 % receiving placebo (p = 0.124, p = 0.043, and p = 0.158, respectively).  In CD-MP, 23.8 % versus 11.1 % of abatacept versus placebo patients were in remission at week 52.  In UC-MP, 12.5 % versus 14.1 % of patients receiving abatacept versus placebo were in remission at week 52.  Safety generally was comparable between groups.  The studies showed that abatacept is not efficacious for the treatment of moderate-to-severe CD or UC.

Kemta et al (2012) evaluated the safety and effectiveness of biologics in patients with active relapsing polychondritis (RP).  These investigators performed a systematic review of the literature using PubMed through December 2010.  MeSH terms and keywords were used relating to RP and biologics.  All papers reporting the efficacy and/or safety of biologics in RP were selected.  Reference lists of included papers were also searched.  All publications were related to case series or isolated case reports.  No randomized controlled trial (RCT) has been performed.  A total of 30 papers that included 62 patients were published.  These patients were treated with TNFα blockers (n = 43), rituximab (n = 11), anakinra (n = 5), tocilizumab (n = 2), and abatacept (n = 1).  The endpoint of treatment differs from 1 publication to the other and therefore made the comparison of efficacy among the various biologics difficult.  Biologics were effective in 27 patients, partially effective in 5 patients, and not effective in 29 patients.  Safety appeared to be good.  However, 4 deaths were recorded (2 sepsis, 1 post-operatively after aortic aneurysm surgery, and 1 after accidental dislocation of the tracheostomy device).  The authors concluded that the experience with biologics in RP is very limited and their real efficacy and indications need to be better defined.  They stated that RCTs, although difficult to perform because of the rarity of RP, are needed to determine the place of biologics in the treatment strategy of this orphan disease.

Wofsy et al (2012) stated that recent lupus nephritis trials have all used different criteria to assess complete response (CR).  These investigators compared several previously proposed criteria using the same data set from a large trial of abatacept in lupus nephritis.  By so doing, they sought: (i) to determine which criteria are most sensitive to differences among treatment groups; and (ii) to further examine the potential of abatacept in lupus nephritis.  Subjects in BMS study number IM101075 received either abatacept or placebo on a background of mycophenolate mofetil and corticosteroids.  Using data from this trial, these researchers assessed CR rates at 12 months according to 5 sets of criteria from: (i) the trial protocol; (ii) the ALMS trial of mycophenolate mofetil; (iii) the LUNAR trial of rituximab; (iv) an ongoing NIH trial of abatacept (ACCESS); and (v) published recommendations of the American College of Rheumatology.  The per-protocol CR definition showed no difference among groups.  In contrast, the ALMS, LUNAR, and ACCESS definitions each showed significantly higher CR rates in both treatment groups relative to control.  The largest differences were observed using the LUNAR criteria (CR rates of 6 % among control subjects, compared to 22 % and 24 % in the 2 abatacept groups).   The authors concluded that the choice of definition of complete response can determine whether a lupus nephritis trial is interpreted as a success or a failure.  This analysis provided an evidence-based rationale for choosing among alternative definitions, and it offered a strong rationale for conducting further studies of abatacept in lupus nephritis.

Elhai et al (2013) evaluated the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy.  A total of 20 patients with SSc with refractory polyarthritis and 7 with refractory myopathy from the EUSTAR (EULAR Scleroderma Trials and Research) network were included: 15 patients received tocilizumab, and 12 patients received abatacept.  All patients with SSc-myopathy received abatacept.  Clinical and biological assessments were made at the start of treatment and at the last infusion.  After 5 months, tocilizumab induced a significant improvement in the 28-joint count Disease Activity Score and its components, with 10/15 patients achieving a European League Against Rheumatism (EULAR) good response.  Treatment was stopped in 2 patients because of inefficacy.  After 11 months' treatment of patients with abatacept, joint parameters improved significantly, with 6/11 patients fulfilling EULAR good-response criteria.  Abatacept did not improve muscle outcome measures in SSc-myopathy.  No significant change was seen for skin or lung fibrosis in the different groups.  Both treatments were well-tolerated.  The authors concluded that in this observational study, tocilizumab and abatacept appeared to be safe and effective on joints, in patients with refractory SSc.  No trend for any change of fibrotic lesions was seen but this may relate to the exposure time and inclusion criteria.  Moreover, they stated that larger studies with longer follow-up are needed to further determine the safety and effectiveness of these drugs in SSc.

Arabshahi et al (2012) reported the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis.  This combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis.

Also, an UpToDate review on “Treatment and prognosis of juvenile dermatomyositis and polymyositis” (Hutchinson and Feldman, 2013) states that “Abatacept is a soluble fusion protein comprised of the extracellular domain of cytotoxic T lymphocyte antigen 4 (CTLA-4) and the Fc portion of immunoglobulin G1 (IgG1).  It binds to CD80/CD86, preventing CD28 binding and thereby downregulating T cell activation.  A 14 year old girl with severe, refractory JDM with ulcerations and calcinosis was reported to have improvement in disease scores, ulcerations, pain medication and glucocorticoid use, and laboratory values after treatment with abatacept and thiosulfate.  The utility of this agent in children with JDM remains to be determined”.

An UpToDate review on “Treatment of psoriasis” (Feldman, 2013) does not mention abatacept as a therapeutic option.

An UpToDate review on “Reactive arthritis (formerly Reiter syndrome)” (Yu, 2013) does not mention abatacept as a therapeutic option.

Weinblatt et al (2013) evaluated the overall safety, including rare events, of intravenous (IV) abatacept treatment in RA.  Data from 8 clinical trials of IV abatacept in RA were pooled.  Safety events were assessed during the short-term (duration less than or equal to 12 months) and cumulative (short-term plus long-term extensions) abatacept treatment periods.  Incidence rates per 100 patient-years were calculated.  Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population.  There were 3,173 IV abatacept-treated patients with 2,331 patient-years of exposure in the short-term periods, and 4,149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period.  Incidence rates for serious infections were low and consistent over time (3.68 for abatacept versus 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period).  Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time.  Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 versus 0.59) and remained low during the abatacept cumulative period (0.73).  SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts.  Autoimmune events were rare and infusion reactions uncommon.  The authors concluded that long-term safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.  (This study addressed the use of abatacept for RA, not PsA.  Moreover, there were no direct comparisons in infection rates between abatacept with anti-TNF alpha agents).

Furthermore, an UpToDate review on "Treatment of psoriatic arthritis" (Gladman and Ritchlin, 2014) lists abatacept as one of the experimental therapies.

De La Mata et al (2011) examined the effectiveness of available drugs in undifferentiated spondyloarthritis (u-SpA).  Systematic review of studies retrieved from Medline (1961 to July 2009), Embase (1961 to July 2009), and Cochrane Library (up to July 2009) was carried out.  A complementary hand-search was also performed.  The selection criteria were as follows: (population) u-SpA patients; (intervention) non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), anti-tumor necrosis factor-α, anakinra, abatacept, bisphosphonates, or thalidomide; (outcome) pain, function, structural damage and quality of life; (study design) randomized controlled trials (RCTs), cohort studies, and case reports; (level of evidence) according to The Oxford Centre for Evidence-based Medicine (update 2009).  An additional narrative review was performed to analyze the effects of drug therapies in patients with spondyloarthritis according new Assessment of Spondyloarthritis International Society criteria.  The following 7 studies were included: 2 RCT, 1 cohort study, and 4 case reports, which included 117 patients with u-SpA (mostly young men).  No evidence related to the effect of NSAIDs or DMARDs on u-SpA patients was found.  Infliximab and etanercept showed some benefit regarding clinical outcomes, function, and quality of life.  Two RCTs reported important benefit of infliximab and adalimumab also in patients with predominantly axial spondyloarthritis.  Rifampicin plus doxycycline improved some clinical outcomes but ciprofloxacin had no benefit.  Anecdotal positive evidence was reported with pamidronate.  No serious adverse events were reported in the retrieved studies.  The authors concluded that low-quality evidence suggested a benefit of tumor necrosis factor α blockers in u-SpA and good-quality evidence in predominantly axial spondyloarthritis.  The use of antibiotics remained controversial.  Moreover, the authors stated that high-quality trials are needed to definitively assess the effect of available drugs in these patients.

Lekpa et al (2012) evaluated the effectiveness of abatacept in patients with axial spondyloarthropathies who had failed TNF-α antagonist therapy.  Consecutive patients fulfilling criteria for active axial spondyloarthropathy, despite at least 2 previous TNF-α antagonists, were treated with abatacept (10 mg/kg) given on days 1, 15, and 29, then every 28 days until week 24.  Clinical and laboratory outcome criteria were assessed monthly for 6 months.  A total of 7 patients were treated and followed, all women (median age of 39 years; median disease duration of 12 years), 5 with ankylosing spondylitis and 2 with undifferentiated spondyloarthropathy.  After 6 months of abatacept therapy, no patient had an at least 50 % decrease in the BASDAI; a single patient had an at least 2 cm decrease in the BASDAI (-3.8 cm; -49.3 %).  No significant changes were observed in pain or patient global assessment scores.  Inflammatory back pain persisted in all 7 patients.  When present, enthesitis improved in most patients.  Improvements in spinal mobility measures occurred in 2 patients.  There were no clinically significant adverse events.  The authors concluded that a 6-month regimen of abatacept did not meaningfully improve disease activity, function, or other disease parameters in 7 patients with axial spondyloarthropathies.  They noted that these preliminary results did not suggest a strong efficacy of abatacept in axial forms of spondyloarthropathies.

Wevers-de Boer et al (2013) stated that undifferentiated arthritis (UA) is defined as an inflammatory oligoarthritis or polyarthritis in which no definitive diagnosis can be made.  These investigators performed a literature review to assess the efficacy of various drug therapies in patients with UA.  The literature search was conducted using electronic databases PubMed, EMBASE and MEDLINE in adults with UA or early arthritis (not fulfilling the American College of Rheumatology (ACR) 1987 or ACR/ EULAR 2010 criteria for rheumatoid arthritis).  Drug therapy consisted of DMARDs, biological agents and oral, intra-muscular or intra-articular corticosteroids.  A total of 9 publications on 8 RCTs, 2 publications on 2 uncontrolled open-label trials, and 7 publications on 3 cohort studies were included.  Temporary treatment with methotrexate (MTX), abatacept and intra-muscular corticosteroids were demonstrated in RCTs with 12 months to 5 years follow-up to be more effective than placebo in suppressing disease activity or radiological progression.  One study suggested that DMARD combination therapy is, at least after 4 months, superior to MTX monotherapy in patients with UA at high-risk of developing persistent arthritis.  The open-label uncontrolled trials and cohort studies also suggested that early treatment may provide immediate suppression of inflammation.  The long-term benefit of early treatment in UA remains unclear.  The authors concluded that patients with UA benefit from early treatment with MTX.  Combining multiple DMARDs or DMARDs with corticosteroids and biological agents may be even more beneficial.  However, which treatment may provide the best results or may alter the disease course has still to be determined.  Moreover, they stated that more RCTs with longer follow-up time are needed.

Yu and colleagues (2013) stated that abatacept (cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin fusion protein [CTLA-4-Ig]) is a co-stimulatory inhibitor that targets B7-1 (CD80).  The present report described 5 patients who had focal segmental glomerulo-sclerosis (FSGS) (4 with recurrent FSGS after transplantation and 1 with primary FSGS) and proteinuria with B7-1 immuno-staining of podocytes in kidney-biopsy specimens.  Abatacept induced partial or complete remissions of proteinuria in these patients, suggesting that B7-1 may be a useful biomarker for the treatment of some glomerulopathies.  The authors concluded that the findings of this study indicated that abatacept may stabilize β1-integrin activation in podocytes and reduce proteinuria in patients with B7-1-positive glomerular disease.(This was a small study of 4 patients with FSGS after transplantation).

In an editorial that accompanied the afore-mentioned study, Haraldsson (2013) stated that “If corroborated, these observations -- and the approach described -- may signal the start of a new era in the treatment of patients with proteinuric kidney disease.  However, only time will tell how many patients will benefit from the proposed podocyte-targeted treatment with abatacept or similar agents”.

Wojciechowski and Vincenti (2011) noted that signaling through the co-stimulatory pathway is critical in the regulation of T cell activation.  Abatacept, a selective co-stimulatory antagonist FDA approved for the treatment of moderate to severe rheumatoid arthritis, binds to CD80 and CD86 on antigen presenting cells, blocking the interaction with CD28 on T cells.  Belatacept, a second generation CTLA4-Ig with 2 amino acid substitutions, has shown considerable promise in clinical transplantation as part of a maintenance immunosuppression regimen.  The authors review summarized the role of co-stimulation in T cell activation, detailed the development of co-stimulation antagonists and highlighted the pertinent clinical trials completed and ongoing utilizing belatacept as part of an immunosuppressive regimen in organ transplantation. 

Riella and Sayegh (2013) stated that the concern about nephrotoxicity with calcineurin inhibitors led to the search of novel agents for immunosuppression.  Based on the requirement of T-cell co-stimulatory signals to fully activated naïve T cells, it became clear that blocking these pathways could be an appealing therapeutic target.  However, some unexpected findings were noticed in the recent clinical trials of belatacept, including a higher rate of rejection, which warranted further investigation with some interesting concepts emerging from the bench.  This review did not mention abatacept as an immunosuppressive agent in organ transplantation.

Alkandari et al (2014) noted that FSGS is a common cause of end-stage renal disease in children.  Focal segmental glomerulo-sclerosis recurrence in renal transplants is a challenging disease, and can cause graft dysfunction and loss.  Different therapies exist with varying responses, from complete remission to resistance to all modes of treatment.  Abatacept was recently introduced as a treatment for primary FSGS in native kidneys and in recurrent disease after transplant.  These researchers presented a pediatric case with immunosuppression-resistant primary NPHS2-negative FSGS recurrence after renal transplant.  The standard therapy for recurrent FSGS (rituximab, plasmapheresis, high-dose cyclosporine, and corticosteroids) was tried but failed to induce remission.  Abatacept (10 mg/kg) was given at 0, 2, and 4 weeks (total, 3 doses) with no good response.  The authors concluded that abatacept may work in patients with B7-1-positive FSGS recurrence and its efficacy is uncertain in disease with B7-1-negative or unknown staining status.

Also, an UpToDate review on “Overview of the management of chronic kidney disease in adults” (Rosenberg, 2014) does not mention the use of abatacept as a therapeutic option.

In a pilot, open-label, proof of concept study, Meiners et al (2014) evaluated the safety and effectiveness of abatacept in patients with early and active primary Sjogren's syndrome (pSS).  All 15 patients (12 women, 3 men) included in the study met the revised American-European Consensus Group criteria for pSS and were biological DMARD-naive.  Patients were treated with 8 intravenous abatacept infusions on days 1, 15 and 29 and every 4 weeks thereafter.  Follow-up was conducted at 4, 12, 24 (on treatment), 36 and 48 weeks (off treatment).  Disease activity was assessed with EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) and EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI).  Several other functional, laboratory and subjective variables were analyzed.  Generalized estimating equations were used to analyze parameters over time.  ESSDAI, ESSPRI, rheumatoid factor and IgG levels decreased significantly during abatacept treatment and increased post-treatment.  Salivary and lacrimal gland function did not change during treatment.  Fatigue and health-related quality of life (HR-QoL) improved significantly during treatment.  No serious side effects or infections were seen.  The authors concluded that in this open-label study, abatacept treatment is effective, safe and well-tolerated, and results in improved disease activity, laboratory parameters, fatigue and HR-QoL in patients with early and active pSS.  These preliminary findings from a pilot, proof of concept study need to be validated by well-designed studies.

In a systematic review, Silva-Fernandez and colleagues (2014) analyzed the current evidence on the therapeutic use of biological agents for the treatment of systemic vasculitis (SV).  Medline, Embase, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to the end of April 2013.  Systematic reviews and meta-analysis, clinical trials, cohort studies, and case series with more than 3 patients were included.  Independent article review and study quality assessment was done by 2 investigators with consensus resolution of discrepancies.  Of 3,447 citations, abstracts, and hand-searched studies screened, 90 were included.  Most of the studies included ANCA-associated vasculitis (AAV) patients and only a few included large vessel vasculitis (LVV) patients.  Rituximab was the most used agent, having demonstrated effectiveness for remission induction in patients with AAV.  A number of studies used different anti-TNFα agents with contrasting results.  A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and tocilizumab were found.  The authors concluded that current evidence on the use of biological therapies for SV is mainly based on uncontrolled, observational data.  Rituximab is not inferior to cyclophosphamide for remission induction in AAV and might be superior in relapsing disease.  Infliximab and adalimumab are effective as steroid-sparing agents.  Etanercept is not effective to maintain remission in patients with granulomatosis with polyangiitis, and serious adverse events have been reported.  For LVV, both infliximab and etanercept had a role as steroid-sparing agents, and tocilizumab might be effective also for remission induction in LVV.

In an open-label study, Langford et al (2014) examined the safety and effectiveness of abatacept in non-severe relapsing granulomatosis with polyangiitis (GPA; also known as Wegener's granulomatosis).  Intravenous abatacept was administered in 20 patients with non-severe relapsing GPA.  Prednisone up to 30 mg daily was permitted within the first 2 months, and patients on methotrexate, azathioprine, or mycophenolate mofetil continued these agents.  Patients remained on study until common closing or early termination.  Of the 20 patients, 18 (90 %) had disease improvement, 16 (80 %) achieved remission (BVAS/WG = 0) at a median of 1.9 months, and 14 (70 %) reached common closing.  Six patients (30 %) met criteria for early termination due to increased disease activity; 3 of 6 achieved remission and relapsed at a median of 8.6 months.  The median duration of remission before common closing was 14.4 months, with the median duration of time on study for all patients being 12.3 months (range of 2 to 35 months); 11 of the 15 (73 %) patients on prednisone reached 0 mg.  Nine severe adverse events occurred in 7 patients, including 7 infections that were successfully treated.  The authors concluded that in this study of patients with non-severe relapsing GPA, abatacept was well-tolerated and was associated with a high frequency of disease remission and prednisone discontinuation.  These preliminary findings from a small study (n = 20) need to be validated by well-designed studies.

Mullighan et al (1999) stated that variation in clinical phenotype is a hallmark of many complex diseases.  The cause of this clinical heterogeneity is unknown, but it may be determined by genetic factors distinct from those conferring disease susceptibility.  Common variable immunodeficiency (CVID) is a complex disease of unknown etiology and diverse clinical manifestations.  These researchers have developed a unified polymerase chain reaction and sequence-specific primer (PCR-SSP) method to simultaneously genotype multiple polymorphisms under identical conditions, and have used this method to test the hypothesis that the clinical phenotype of CVID is determined by immunoregulatory gene polymorphism.  A total of 23 polymorphisms in 13 genes were studied in 163 CVID patients.  Vitamin D receptor and IL-6 alleles were associated with immunophenotypic abnormalities characteristic of more severe disease; and tumor necrosis factor and IL-10 alleles conferred susceptibility to the granulomatous form of CVID in an interacting fashion.  The authors concluded that these findings demonstrated that different clinical features of a disease may have unique pathogenetic abnormalities, determined by multiple interacting genetic factors.  The ease of application of this efficient, robust genotyping technique to polymorphisms throughout the genome will make it a powerful tool in the investigation of the genetic basis of phenotypic variability in a wide variety of diseases. 

Adams et al (2012) noted that parvovirus B19 infection in healthy hosts is self-limited, but persistent infection has been described in patients with cellular immune defects.  These investigators reported the case of a 6-year old boy who presented with a 6-month history of weight loss and malaise and a 1-month history of fever and polyarticular arthritis.  Parvovirus DNA was detected in plasma at 10 300 copies/ml.  Levels of immunoglobulin (Ig)G, IgA, IgM, IgG-1, and IgG-2 were low, and antibody responses to vaccine antigens were impaired.  HIV antibody and DNA PCR were negative, and the patient had normal immunophenotype, mitogen stimulation response, CD40 ligand and inducible co-stimulator expression, transmembrane activator and CAML interactor sequencing, genomic analysis, and fluorescent in situ hybridization for deletions at 22q11.2.  Common variable immunodeficiency was diagnosed and replacement therapy with immune globulin intravenous was initiated.  The parvovirus DNA level declined by 50 % over 3 months and was undetectable at 15 months.  Constitutional symptoms improved but arthritis persisted and eosinophilic fasciitis eventually developed.  The authors concluded that this case demonstrated that persistent parvovirus infection may be a presenting feature of humoral immune deficiency and can mimic juvenile rheumatoid arthritis.  The infection may respond to immune globulin intravenous therapy. 

Furthermore, UpToDate reviews on “Treatment and prognosis of common variable immunodeficiency” (Ahn and Cunningham-Rundles, 2014) and “Common variable immunodeficiency in children” (Hogan and Wilson, 2014) do not mention abatacept as a therapeutic option.


According to the Food and Drug Administration-approved labeling, abatacept may be used as monotherapy or concomitantly with disease-modifying anti-rheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists (adalimumab, etanercept, infliximab).  It is also not recommended for use concomitantly with anakinra, an interleukin-1 receptor antagonist.

According to the FDA-approved labeling for Orencia, for adult patients with RA, abatacept should be administered as a 30-min intravenous infusion utilizing the weight range-based dosing specified in the table.  Following the initial administration, abatacept should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.

Table: Dose of abatabept in adult RA

Body Weight Patient Dose
Less than 60 kg 500 mg
60 to 100 kg 750 mg
Greater than 100 kg 1,000 mg

Key: kg = kilograms; mg = milligrams 

Source: Orencia Prescribing Information.

According to the FDA-approved labeling for Orencia, the recommended dose of abatacept for patients 6 to 17 years of age with juvenile idiopathic arthritis who weigh less than 75 kg is 10 mg/kg calculated based on the patient's body weight at each administration.  Pediatric patients weighing 75 kg or more should be administered abatacept following the adult dosing regimen, not to exceed a maximum dose of 1,000 mg.  Abatacept should be administered as a 30-min intravenous infusion.  Following the initial administration, abatacept should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter.

If a response to abatacept is not present within 6 months of treatment, the potential benefits of continuing treatment, the known and potential risks, and the therapeutic alternatives should be considered (Bromilow, 2009).

Table: Targeted Immune Modulators

Brand Name Generic Name FDA Labeled Indications
Actemra tocilizumab

Juvenile idiopathic arthritis

Rheumatoid arthritis

Systemic juvenile idiopathic arthritis

Cimzia certolizumab

Ankylosing spondylitis

Crohn's disease

Psoriatic arthritis

Rheumatoid arthritis

Cosentyx secukinumab Plaque psoriasis
Enbrel etanercept

Ankylosing spondylitis

Juvenile idiopathic arthritis

Plaque psoriasis

Psoriatic arthrits

Rheumatoid arthritis

Entyvio vedolizumab

Crohn's disease

Ulcerative colitis

Humira adalimumab

Ankylosing spondylitis

Crohn's disease

Juvenile idiopathic arthritis

Plaque psoriasis

Psoriatic arthritis

Ulcerative colitis

Rheumatoid arthritis

Kineret anakinra Rheumatoid arthritis
Orencia abatacept

Juvenile idiopathic arthritis

Rheumatoid arthritis

Otezla apremilast

Plaque psoriasis

Psoriatic arthritis

Remicade infliximab

Ankylosing spondylitis

Crohn's disease

Psoriatic arthritis

Plaque psoriasis

Rheumatoid arthritis

Ulcerative colitis

Rituxan rituximab Rheumatoid arthritis
Simponi golimumab

Ankylosing spondylitis

Psoriatic arthritis

Ulcerative colitis

Rheumatoid arthritis

Ulcerative colitis

Simponi Aria golimumab intravenous Rheumatoid arthritis
Stelara ustekinumab

Plaque psoriasis

Psoriatic arthritis

Xeljanz tofacitinib Rheumatoid arthritis
CPT Codes/ HCPCS Codes / ICD-9 Codes
Other CPT codes related to the CPB:
71010 - 71035 Chest x-ray
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)
HCPCS codes covered if selection criteria are met:
J0129 Injection, abatacept, 10 mg (code may be used for medicare when drug administered under the direct supervision of a physician, not for use when drug is self administered) [if the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulators]
ICD-9 codes covered if selection criteria are met:
714.0 - 714.2 Rheumatoid arthritis [adults only] [if the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulators]
714.30 - 714.31 Polyarticular juvenile rheumatoid arthritis [moderate or severely active for age 6 years and older]
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
099.3 Reiter's disease
136.1 Behcet's syndrome
250.0 - 250.9
(with 5th digit of 1 or 3)
Diabetes mellitus type I
279.06 Common variable immunodeficiency
279.50 - 279.53 Graft-versus-host disease
340 Multiple sclerosis
446.4 Wegener's granulomatosis
446.7 Takayasu's Disease [Takayasu's arteritis]
555.0 - 555.9 Regional enteritis [Crohn's disease]
556.0 - 556.9 Ulcerative colitis
580.81 Acute glomerulonephritis in diseases classified elsewhere [Lupus nephritis]
582.1 Chronic glomerulonephritis with lesion of membranous glomerulonephritis
583.81 Nephritis and nephropathy, not specified as acute or chronic, in diseases classified elsewhere [lupus nephritis]
696.0 - 696.1 Psoriatic arthropathy and other psoriasis
696.1 Other psoriasis
710.0 Systemic lupus erythematosus
710.1 Systemic sclerosis
710.2 Sicca syndrome
710.3 Dermatomyositis [Juvenile]
714.32 Pauciarticular juvenile rheumatoid arthritis
714.33 Monoarticular juvenile rheumatoid arthritis
716.50 - 716.59 Unspecified polyarthropathy or polyarthritis
720 Ankylosing spondylitis
721.90 Spondylosis of unspecified site without mention of myelopathy
733.99 Other specified disorders of bone and cartilage [relapsing polychondritis]
CPT Codes/ HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015:
Other CPT codes related to the CPB:
71010 – 71035 Chest x-ray
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)
HCPCS codes covered if selection criteria are met:
J0129 Injection, abatacept, 10 mg (code may be used for Medicare when drug administered under the direct supervision of a physician, not for use when drug is self administered) [if the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulators]
ICD-10 codes covered if selection criteria are met:
M05.00 - M05.09, M05.20 - M06.39, M06.80 - M06.9 Rheumatoid arthritis [adults only] [if the member has a contraindication, intolerance or incomplete response to at least 2 of the least cost brands of targeted immune modulators]
M08.00 - M08.09, M08.20 - M08.3 Juvenile rheumatoid arthritis [moderate or severely active for age 6 years and older]
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
D83.0 - D83.9 Common variable immunodeficiency
D89.810 - D89.813 Graft-versus-host disease
E10.10 - E10.9 Type 1 diabetes mellitus
G35 Multiple sclerosis
K50.00 - K50.919 Crohn's disease (regional enteritis)
K51.00 - K51.919 Ulcerative colitis
L40.0 - L40.9 Psoriasis
M02.30 - M02.39 Reiter's disease
M08.40 - M08.48 Pauciarticular juvenile rheumatoid arthritis
M13.0 Polyarthritis, unspecified
M31.30 - M31.31 Wegener's granulomatosis
M31.4 Aortic arch syndrome [Takayasu arteritis]
M32.0 - M32.9 Systemic lupus erythematosus (SLE)
M33.00 - M33.99 Dermatopolymyositis
M34.0 - M34.9 Systemic sclerosis [scleroderma]
M35.00 - M35.09 Sicca syndrome
M35.2 Behcet's disease
M45.0 - M45.9 Ankylosing spondylitis
M47.819 Spondylosis without myelopathy or radiculopathy, site unspecified
M94.1 Relapsing polychondritis
N03.3 Chronic nephritic syndrome with diffuse mesangial proliferative glomerulonephritis
N08 Glomerular disorders in diseases classified elsewhere

The above policy is based on the following references:
    1. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis: Arthritis Rheum. 1996;39(5):713-723. Available at: Accessed January 13, 2006.
    2. Dumont FJ. Technology evaluation: Abatacept, Bristol-Myers Squibb. Curr Opin Mol Ther. 2004;6(3):318-330.
    3. Voll RE, Kalden JR. Do we need new treatment that goes beyond tumor necrosis factor blockers for rheumatoid arthritis? Ann N Y Acad Sci. 2005;1051:799-810.
    4. Pollard L, Choy E. Rheumatoid arthritis: Non-tumor necrosis factor targets. Curr Opin Rheumatol. 2005;17(3):242-246.
    5. Ruderman EM, Pope RM. The evolving clinical profile of abatacept (CTLA4-Ig): A novel co-stimulatory modulator for the treatment of rheumatoid arthritis. Arthritis Res Ther. 2005;7 Suppl 2:S21-S25.
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    11. Horneff G Importance of the new biologicals and cytokine antagonists in the treatment of juvenile idiopathic arthritis (JIA). Z Rheumatol. 2005;64(5):317-326.
    12. National Horizon Scanning Centre (NHSC). Abatacept (CTLA4Ig) for rheumatoid arthritis unresponsive to current therapies - horizon scanning review. Birmingham, UK: NHSC; 2004:1-6.
    13. Allison C. Abatacept as add-on therapy for rheumatoid arthritis. Issues in Emerging Health Technologies Issue 73. Ottawa, ON: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); September 2005:1-4.
    14. Emery P, Kosinski M, Li T, et al. Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life. J Rheumatol. 2006;33(4):681-689.
    15. Simpson D. New developments in the prophylaxis and treatment of graft versus host disease. Expert Opin Pharmacother. 2001;2(7):1109-1117.
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    17. Schiff M, Keiserman M, Codding C, et al. The efficacy and safety of abatacept or infliximab in RA patients with an inadequate response to MTX: Results from a 1-year double-blind, randomized, placebo-controlled trial. Oral presentation at the 2006 American College of Rheumatology Annual Scientific Meeting, Washington, DC, November 14, 2006, L43.
    18. Bristol-Myers Squibb Co. Orencia (abatacept) lyophilized powder for intravenous injection. Full Prescribing Information. B5-B0001-04-08. Princeton, NJ: Bristol-Myers; April 2008.
    19. Waknine Y. Abatacept (Orencia) approved for polyarticular juvenile idiopathic arthritis. Medscape Medical News. New York, NY: Medscape LLC; April 17, 2008.
    20. National Institute for Health and Clinical Excellence (NICE). Abatacept for the treatment of rheumatoid arthritis. Technology Appraisal Guidance 141. London, UK: NICE; 2008.
    21. D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007;369(9561):587-596.
    22. Ruperto N, Lovell DJ, Quartier P, et al; Paediatric Rheumatology INternational Trials Organization; Pediatric Rheumatology Collaborative Study Group. Abatacept in children with juvenile idiopathic arthritis: A randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008;372(9636):383-391.
    23. Maxwell L, Singh JA. Abatacept for rheumatoid arthritis. Cochrane Database Syst Rev. 2009;(4):CD007277.
    24. Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: An overview of Cochrane reviews. Cochrane Database Syst Rev. 2009;(4):CD007848.
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    26. Schiff M, Keiserman M, Codding C, et al. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: A phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008;67(8):1096-1103.
    27. Russell A, Beresniak A, Bessette L, et al. Cost-effectiveness modeling of abatacept versus other biologic agents in DMARDS and anti-TNF inadequate responders for the management of moderate to severe rheumatoid arthritis. Clin Rheumatol. 2009;28(4):403-412.
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