Secukinumab (Cosentyx)

Number: 0905

Least Cost Medically Necessary Brands

Cosentyx (secukinumab) brand is more costly to Aetna than other brands of targeted immune modulators (“least cost brands of targeted immune modulators”) for certain indications. There is a lack of reliable evidence that Cosentyx is superior to the least cost brands of targeted immune modulators for the medically necessary indications listed below. Therefore, Aetna considers Cosentyx to be medically necessary for members who have a contraindication, intolerance or ineffective response to the least cost brands of targeted immune modulators per criteria below:

  • Moderate to severe plaque psoriasis

    For the treatment of moderate to severe plaque psoriasis, member has a contraindication, intolerance or ineffective response to all of the following least cost brands (one-month trial): Humira, Ilumya, Otezla, Skyrizi, Stelara, Taltz, and Tremfya.

Policy

Aetna considers secukinumab (Cosentyx) 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 screening testing for TB* within 6 months of initiating therapy for persons who are naiive to biologics, and repeated yearly for members with risk factorsFootnotes for Risk factors for TB include** for TB that are continuing therapy with biologics:

  1. Moderate to severe plaque psoriasis (PsO) or active psoriatic arthritis (PsA) when member meets criteria in CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators

  2. 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.

Aetna considers continuation of secukinumab (Cosentyx) medically necessary for all members (including new members) who are using secukinumab for an indication outlined above and who achieve or maintain positive clinical response as evidenced by low disease activity or improvement in signs and symptoms of the condition.

Aetna considers the combinational use of secukinumab with other targeted immune modulators for ankylosing spondylitis experimental and investigational because of insufficient evidence of effectiveness and safety.

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

  • Actinic granuloma
  • Alopecia areata
  • Alzheimer disease
  • Atopic dermatitis
  • Behcet's disease-related uveitis
  • Diabetes mellitus type-I
  • Dry eye
  • Erythrodermic psoriasis
  • Granuloma annulare
  • Granulomatous interstitial nephritis
  • Hepatocellular carcinoma
  • Hidradenitis suppurativa
  • Ichthyoses
  • Interstitial granulomatous dermatitis
  • Non-infectious uveitis
  • Non-radiographic axial spondyloarthritis
  • Palmoplantar psoriasis
  • Papulopustular rosacea
  • Parkinson's Disease
  • Pityriasis rubra pilaris
  • Pyoderma gangrenosum
  • Rheumatoid arthritis
  • SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome
  • Vitiligo.

Aetna considers secukinumab gene therapy experimental and investigational because its effectiveness has not been established.

Footnotes* Secukinumab is contraindicated and considered not medically necessary for persons with active TB or untreated latent disease. If the screening test for TB is positive, there must be further testing to confirm there is no active disease. Do not administer secukinumab to persons with active TB infection. If there is latent disease, TB treatment must be started before initiation of secukinumab.

Footnotes** 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, 2016).

Dosing Recommendations

Secukinumab (Cosentyx) is available for subcutaneous injection:

  • Injection: 150 mg/mL solution in a single-use Sensoready pen
  • Injection: 150 mg/mL solution in a single-use prefilled syringe
  • For Injection: 150 mg, lyophilized powder in a single-use vial for reconstitution for healthcare professional use only

For dosing recommendations on plaque psoriasis (PsO) and psoriatic arthritis (PsA), see CPB 0658 - Psoriasis and Psoriatic Arthritis: Targeted Immune Modulators.

Ankylosing Spondylitis

For persons with ankylosing spondylitis, administer Cosentyx with or without a loading dose by subcutaneous injection. The recommended dosage:
  • With a loading dose is 150 mg at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter;
  • Without a loading dose is 150 mg every 4 weeks.

Source: Novartis, 2018

Background

Secukinumab (Cosentyx) is a human interleukin-17A antagonist which is U.S. Food and Drug Administration (FDA) approved for the treatment of:

  • adults with active ankylosing spondylitis (AS)
  • moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy; and
  • adults with active psoriatic arthritis (PsA)

Most common adverse reactions (greater than 1%) are nasopharyngitis, diarrhea, and upper respiratory tract infection.

Prior to initiating Cosentyx, individuals are evaluated for tuberculosis (TB) infection. Do not administer Cosentyx to persons with active TB infection. Initiate treatment of latent TB prior to administering Cosentyx. Consider anti-TB therapy prior to initiation of Cosentyx in persons with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Persons receiving Cosentyx should be monitored closely for signs and symptoms of active TB during and after treatment (Novartis, 2018).

Ankylosing Spondylitis

Ankylosing spondylitis is a chronic immune-mediated inflammatory disease characterized by spinal inflammation, progressive spinal rigidity, and peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key inflammatory cytokine in the development of ankylosing spondylitis, the prototypical form of spondyloarthritis. Secukinumab is an anti-interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis. 

Baeten et al (2015) reported on two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. In two double-blind trials, investigators randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn's disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

In a phase II study, Baeten et al (2013) assessed the efficacy and safety of the anti-IL-17A monoclonal antibody secukinumab in treating patients with active ankylosing spondylitis. Investigators did a randomized double-blind proof-of-concept study at eight centers in Europe (four in Germany, two in the Netherlands, and two in the UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either intravenous secukinumab (2×10 mg/kg) or placebo, given 3 weeks apart. Randomization was done with a computer-generated block randomization list without a stratification process. The primary efficacy endpoint was the percentage of patients with a 20% response according to the Assessment of SpondyloArthritis international Society criteria for improvement (ASAS20) at week 6 (Bayesian analysis). Safety was assessed up to week 28. In this study, 37 patients with moderate-to-severe ankylosing spondylitis were screened, and 30 were randomly assigned to receive either intravenous secukinumab (n=24) or placebo (n=6). The final efficacy analysis included 23 patients receiving secukinumab and six patients receiving placebo, and the safety analysis included all 30 patients. At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99·8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group.

Other 

There are clinical trials regarding the use of secukinumab for the treatment of various diseases/conditions including alopecia areata, Alzheimer disease, atopic dermatitis, diabetes mellitus type-I, dry eye, hidradenitis suppurativa, ichthyoses, non-infectious uveitis, non-radiographic axial spondyloarthritis, palmoplantar psoriasis, papulopustular rosacea, and rheumatoid arthritis.

Alopecia Areata

Ramot and associates (2018) noted that IL-17 has been implicated in the pathogenesis of a large number of inflammatory and autoimmune conditions, including skin disorders such as psoriasis. Recently, much data has accumulated on the possible role of IL-17 in the pathogenesis of alopecia areata (AA). In this review, the available information on the connection between AA and IL-17 is described. While IL-17 levels are consistently reported to be elevated in the serum and lesional skin of AA patients, there is no clear connection between IL-17 levels and disease severity or duration. Some evidence has suggested an association between IL-17 and an early-onset disease, although this awaits further confirmation. While there is enough information to support clinical trials with IL-17-targeted treatments, it is possible that they will be effective only in a subset of AA patients. Further studies are warranted to better delineate the exact role of IL-17 in AA pathogenesis.

Guttman-Yassky and colleagues (2018) stated that AA is a common form of non-scarring hair loss.  The pathogenesis of AA is believed to involve multiple inflammatory cytokines, including possibly IL-17A.  In a prospective, randomized, double-blinded pilot study, these researchers evaluated the safety and efficacy of the IL-17A antagonist secukinumab in AA.  A total of 11 subjects were treated with either secukinumab (n = 7) or placebo (n = 4) subcutaneously at weeks 0, 1, 2, 3, 4 and every 4 weeks thereafter until (inclusive of) week 20.  The primary end-point for the study was the percentage of patients achieving SALT50 at 24 weeks; 3 subjects out of 11 completed the study through the primary end-point, and thus, these investigators used the last observation carried forward method to analyze the missing data.  At the primary end-point or last completed observation, 0 % (0/7) of the secukinumab-treated subjects achieved a 50 % reduction in SALT score (SALT50), and likewise, 0 % (0/4) of the placebo-treated subjects achieved SALT50.  In the secukinumab group, 1 (14.3 %) subject had some hair regrowth, 1 (14.3 %) subject had worsening hair loss, and 5 (71.4 %) subjects had no change in response to treatment.  No adverse events (AEs) attributable to the study drug were observed.  The authors concluded that the lack of a therapeutic response to most of the treated patients suggested that the TH17/IL-17 axis likely has no pathogenic role in AA and an alternative therapeutic approach should be considered for this disease.  However, due to the low statistical power of this study, future studies may be needed to corroborate these findings.

Behcet's Disease-Related Uveitis

Sota and colleagues (2018) stated that intra-ocular inflammation is one of the more relevant complications of Behcet's disease (BD), which tends to respond poorly to different medications.  The ocular histopathologic changes are basically identical to those occurring in other organs and consist in a necrotizing leukocytoclastic obliterative vasculitis, which is probably immune complex-mediated and affects both arteries and veins of all sizes.  There are growing evidences showing the potential role of biologic agents other than anti-tumor necrosis factor-alpha (TNF-α) agents in the management of ocular-BD, which have been collected in this review, including IL-1 and IL-6 blockade, secukinumab, ustekinumab, daclizumab, rituximab, and alemtuzumab.  The authors concluded that further large studies are needed to fully elucidate and establish the effectiveness of these different tools in the refractory ocular manifestations of BD.

Erythrodermic Psoriasis

Weng and co-workers (2018) presented a case series on the use of secukinumab for the treatment of erythrodermic psoriasis (EP).  However, an UpToDate review on “Erythrodermic psoriasis in adults” (Hawkes and Duffin, 2018) states that “Small studies and case reports provide preliminary support for the use of newer biologic medications for the treatment of erythrodermic psoriasis, including ustekinumab, ixekizumab, secukinumab, and golimumab.  While these novel therapies represent a group of medications likely to be effective in the treatment of erythrodermic psoriasis, subsequent larger studies are necessary prior to a recommendation for the routine use of these therapies”.

Damiani and colleagues (2019) stated that EP is a dermatological emergency and its treatment with secukinumab is still controversial.  Furthermore, no data exist regarding the prognostic value of drug abuse in such a condition.  These researchers carried out a retrospective, multi-center, international, pilot study, enrolling a sample of EP patients (body surface area [BSA] > 90 %) who were treated with secukinumab (300 mg) during the study period from December 2015 to December 2018.  Demographics and clinical data were collected.  Drug abuses were screened and, specifically, smoking status (packages/year), cannabis use (application/week) and alcoholism-tested with the Alcohol Use Disorders Identification Test (AUDIT)-were assessed.  All patients were followed for up to 52 weeks.  These investigators enrolled 13 EP patients, 9 men, and 4 women, with a median age of 40 (28 to 52) years.  Patients naïve to biologic therapy were 3/13.  Regarding drug use, 7 patients had a medium-high risk of alcohol addiction, 3 used cannabis weekly, and 7 were smokers with a pack/year index of 295 (190 to 365).  The response rate to secukinumab was 10/13 patients with a median time to clearance of 3 weeks (1.5 to 3). No recurrences were registered in the 52-week follow-up and a PASI score of 90 was achieved.  The entire cohort of non-responders (n = 3) consumed at least 2 drugs of abuse (alcohol, smoking or cannabis).  Non-responders were switched to ustekinumab and obtained a PASI 100 in 24 weeks.  The authors concluded that although not conclusive, these preliminary findings in EP patients treated with secukinumab enlightened 2 presently unmet needs: the need of therapy-specific biomarkers/prognostic factors and the prevalence of drug use in EP.  These researchers stated that secukinumab may be a safe and effective treatment in EP, however, larger studies are needed to validate these findings.

Granuloma Annulare and Related Cutaneous, Granulomatous Conditions

Chen and associates (2019) stated that granuloma annulare (GA), a benign inflammatory skin disease, is considered a Th1-type delayed hypersensitivity reaction.  Localized GA is likely to resolve spontaneously, whereas disseminated GA (DGA) may persist for decades and can be resistant to treatment.  Biologics including TNF-α inhibitors have been proposed and utilized as salvage therapy for GA and other related diseases, actinic granuloma (AG), and interstitial granulomatous dermatitis (IGD).  These investigators carried out a systematic review using the combination of search terms "granuloma annulare", "interstitial granulomatous dermatitis", or "actinic granuloma" and either "biologics", "etanercept", "adalimumab", "infliximab", "ustekinumab", "ixekizumab", "secukinumab", "guselkumab", "golimumab", "brodalumab", "tildrakizumab" or "certolizumab" from 1970 to 2017.  Review of the literature revealed that 79.3 % of the patients with GA, IGD, or AG who had been treated with TNF-α inhibitor therapy showed a clinical response.  The authors concluded that TNF-α inhibitor therapy has been used to treat chronic GA, IGD, and AG that involved extensive BSA.  However, the literature is limited to case series lacking control groups.  These researchers stated that RCTs are needed to establish evidence-based treatment of GA and related cutaneous, granulomatous conditions.

Granulomatous Interstitial Nephritis

Sandys and associates (2018) stated that TNF-α inhibitors are frequently used for the treatment of immune-mediated diseases.  Conversely, cytokine therapy has the potential to paradoxically induce autoimmunity.  A number of case-reports have emerged concerning sarcoid-like granulomatosis secondary to TNF-α therapy, an adverse effect that typically affects the pulmonary and cutaneous systems.  Granulomatous interstitial nephritis (GIN) is a relatively unknown, relatively under-reported consequence of adalimumab therapy that can have important clinical implications.  The authors concluded that this was the 1st case-report of GIN secondary to anti-TNF-α therapy necessitating a prolonged period of dialysis and the 1st report demonstrating the successful use of secukinumab as an alternative immunomodulatory agent.

Hepato-Cellular Carcinoma

Xu and co-workers (2018) previously demonstrated that IL-17A is associated with the progression of hepato-cellular carcinoma (HCC).  However, its role in the invasion-metastasis cascade of HCC and the efficacy of IL-17A-targeting therapeutics in HCC remain largely unknown.  In this study, these researchers found that IL-17A promoted intra-hepatic and pulmonary metastases of HCC cells in an orthotopic implant model.  Moreover, the results showed that IL-17A induced epithelial-mesenchymal transition (EMT) and promoted HCC cell colonization in-vitro and in-vivo, and the role of IL-17A in invasion-metastasis was dependent on activation of the AKT pathway.  Remarkably, combined therapy using both secukinumab and sorafenib exhibited better inhibition on tumor growth and metastasis compared to sorafenib monotherapy.  Additionally, the combination of intra-tumoral IL-17A+ cells and E-cadherin predicted the outcome of patients with HCC at an early stage after hepatectomy based on tissue microarray and immunohistochemistry.  The authors concluded that these findings revealed that IL-17A induced early EMT and promoted late colonization of HCC metastasis by activating AKT signaling.  They stated that secukinumab is a promising candidate for clinical development in combination with sorafenib for the management of HCC.

Hidradenitis Suppurativa

Matusiak and associates (2017) noted that biologics appeared to offer a promising non-surgical approach in hidradenitis suppurativa (HS), especially in disease with highly pronounced inflammation.  Recent studies revealed increased expression of a broad range of cytokines in lesional HS skin, including IL-17.  This study was undertaken to determine IL-17 serum levels in this group of patients.  This study was conducted on a group of 86 patients between 16 and 72 years of age with HS.  A total of 86 matched healthy volunteers constituted the control group.  Enzyme-linked immunosorbent assay (ELISA) kits were used to quantify IL-17 serum concentration.  The mean IL-17 serum level of patients with HS was 3.68 ± 2.08 pg/ml, which was significantly elevated (p < .0001) compared with that found in healthy volunteers (2.5 ± 1.11 pg/ml).  Moreover, there was a tendency toward higher serum concentrations of IL-17 in patients with more advanced disease (p = 0.005).  Disease duration; patient sex, age, and body mass index (BMI); and smoking habits were not determining factors for IL-17 serum concentration.  The authors concluded that in light of the findings and literature on increased expression of IL-17 in HS lesions, evaluating the clinical effectiveness of using anti-IL-17 agents in the treatment of patients with HS is justified.  The major drawbacks of this study were:
  1. the use of hospital-based study population, and
  2. the lack of post-treatment assessment.

Thorlacius and colleagues (2018) stated that an inappropriate immunologic response to an unknown antigen has been suggested to play a role in the pathogenesis of HS.  Studies have identified elevated levels of several pro-inflammatory cytokines, including IL-17A and TNF-α, nominating these as possible therapeutic targets.  Secukinumab is an Il-17A monoclonal antibody, which binds to Il-17A and inhibits the cytokine interaction with the Il-17 receptors, inhibiting the inflammatory cascade.  These researchers reported on a case of a 47-year old man, with Hurley Stage III lesions at the neck, axillae, breasts, genital skin and buttocks, who had experienced only temporary benefit from different medical treatments over the years.  After 12 weeks of treatment with secukinumab the number of lesions reported by the patient within the period of the last 4 weeks was reduced from 23 to 7, pain visual analog scale (VAS) was reduced from 5 to 3 and pain/utility/handicap VAS was reduced from 7 to 4.  The authors concluded that these findings may be taken to imply that IL-17 blockade could provide a possible therapeutic approach in HS.

Palmoplantar Psoriasis

In a double-blinded, randomized controlled trial (RCT), Gottlieb and colleagues (2017) evaluated the safety and effectiveness of secukinumab in patients with palmoplantar psoriasis.  A total of 205 participants were randomized in a 1:1:1 manner to secukinumab 300-mg, 150-mg, or placebo.  The primary end-point was Palmoplantar Investigator's Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16.  At week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300-mg (33.3 %) and 150-mg (22.1 %) was superior to the percentage achieved with placebo (1.5 %, p < 0.001); ppPsoriasis Area Severity Index (ppPASI) was significantly reduced with secukinumab 300-mg (-54.5 %) and 150-mg (-35.3 %) compared with placebo (-4.0 %, p < 0.001).  Dermatology Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups were also significantly higher compared with placebo at week 16 (p < 0.01) and pain and function of palms and soles was markedly improved with secukinumab as measured by the palmoplantar Quality-of-Life Instrument.  Secukinumab 300-mg consistently showed the best outcomes.  The safety profile was favorable and similar to previous studies.  The authors concluded that in GESTURE, the largest RCT in palmoplantar psoriasis, secukinumab demonstrated the greatest efficacy to-date for treating difficult-to-treat psoriasis.  Moreover, these investigators stated that the findings of this study reinforced the difficult-to-treat nature of palmoplantar psoriasis compared with psoriasis on other locations of the body where higher rates of efficacy are more readily achieved.  Furthermore, it highlighted the need for more research given the paucity of RCTs dedicated to palmoplantar psoriasis to-date.  The main drawback of this study was the lack of active comparator. 

Parkinson's Disease

Sommer and associates (2018) noted that Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of mid-brain neurons (MBNs).  Recent evidence suggested contribution of the adaptive immune system in PD.  These investigators showed a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD.  Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in post-mortem PD brain tissues.  These researchers modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls.  After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by up-regulation of IL-17 receptor (IL-17R) and NFκB activation.  Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death.  The authors concluded that these findings indicated a critical role for IL-17-producing T lymphocytes in sporadic PD.

Pityriasis Rubra Pilaris

Gauci and colleagues (2016) stated that pityriasis rubra pilaris (PRP) is a heterogeneous inflammatory skin disease characterized by follicular papules, orange palmoplantar keratoderma, and erythematous scaly patches with islands of skin sparing.  Type II PRP is a rare, severe, chronic form of PRP presenting atypical features including long disease duration, palmoplantar keratoderma, ichthyosiform scaling, eczematous areas, and resistance to therapy.  These investigators reported on the case of a 33-year old woman with a childhood history of hydronephrosis secondary to vesico-ureteral reflux who had a 9-year history of erythroderma with confluent folliculo-centric erythematous scaly plaques, islands of sparing, orange palmoplantar hyperkeratosis, and eczematous lesions.  Previous unsuccessful treatments, given more than 3 months, included topical corticosteroids, acitretin, photochemotherapy, cyclosporine, methotrexate, infliximab, ustekinumab, intravenous immunoglobulin (IVIG), and omalizumab.  Prednisone was efficient, but the patient experienced relapse with less than 0.5 mg/kg/day.  The condition partially improved using cyclosporine (5 mg/kg/day) in association with 10-mg prednisone.  After informed consent, secukinumab was initiated in association with cyclosporine and 10-mg of prednisone.  The patient received 5 subcutaneous 300-mg weekly injections followed by once-monthly injections.  After 4 weeks, secukinumab allowed a significant and prompt clinical response and quality-of-life (QOL) improvement.  Psoriasis area and severity index and dermatologic life quality index score, respectively, decreased from 27.6 to 5.6 and from 30 to 15 after 4 injections.  Secukinumab was well-tolerated except an oral and esophageal candidiasis (treated with fluconazole for 14 days).  Secukinumab was highly effective on clinical symptoms and QOL, without recurrence of PRP lesions with a 6-month follow-up.  These researchers reported that secukinumab induced pruritus relief after 1 week of treatment and improvement of erythematous plaques and palmoplantar keratoderma after 2 weeks of treatment.  They stated that secukinumab could be considered an alternative therapeutic option for refractory type II PRP; further studies are needed to clarify the pathogenic role of IL-17 axis in PRP.

Pyoderma Gangrenosum

Moreno García and colleagues (2019) presented a case report on the use of secukinumab for the treatment of pyoderma gangrenosum.  However, an UpToDate review on “Pyoderma gangrenosum: Treatment and prognosis” (Schadt, 2018) does not mention secukinumab as a therapeutic option.

Rheumatoid Arthritis

In a phase-III, randomized, double-blind, active comparator- and placebo-controlled clinical trial, Blanco and colleagues (2017) evaluated the safety and effectiveness of secukinumab in patients with active rheumatoid arthritis (RA) who had an inadequate response to or intolerance of TNF inhibitors.  A total of 551 patients were randomized (1:1:1:1) to receive intravenous secukinumab at a dose of 10 mg/kg (at baseline and weeks 2 and 4) followed by subcutaneous secukinumab at a dose of either 150-mg or 75-mg every 4 weeks or, alternatively, abatacept or placebo on the same dosing schedule.  The primary end-point was the proportion of patients achieving 20 % improvement in disease activity according to the American College of Rheumatology response criteria (ACR20) at week 24 in the secukinumab 150-mg or 75-mg treatment groups as compared with placebo.  Key secondary end-points included change from baseline to week 24 in the Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) and the Health Assessment Questionnaire disability index (HAQ DI), as well as the ACR 50 % improvement (ACR50) response rate at week 24.  The primary efficacy end-point was met in patients receiving 150 mg secukinumab, in whom the ACR20 response rate at week 24 was significantly higher than that in the placebo group.  The ACR20 response rates at week 24 were 30.7 % in patients receiving 150 mg secukinumab (p = 0.0305), 28.3 % in those receiving 75 mg secukinumab (p = 0.0916), and 42.8 % in those receiving abatacept, compared with 18.1 % in the placebo group.  A significant reduction in the DAS28-CRP was seen in patients treated with 150 mg secukinumab (p = 0.0495), but not in patients treated with 75 mg secukinumab.  Improvements in the HAQ DI and ACR50 response rates were not significant in the 2 secukinumab dose groups compared with the placebo group.  The overall safety profile was similar across all treatment groups.  The authors concluded that secukinumab at a dose of 150-mg resulted in improvement in signs and symptoms and reduced disease activity in patients with active RA who had an inadequate response to TNF inhibitors.  Improvements observed with abatacept were numerically higher than with secukinumab.  There were no new or unexpected safety signals with secukinumab in this study.

An UpToDate review on “Treatment of rheumatoid arthritis in adults resistant to initial nonbiologic DMARD therapy” (Cohen and Cannella, 2017) does not mention secukinumab as a therapeutic option.

In a randomized, double-blind, placebo-controlled phase-III clinical trial, Tahir and associates (2017) evaluated the safety and efficacy of secukinumab in patients with active RA who had an inadequate response to, or intolerance of TNF-inhibitors.  A total of 637 patients were randomized (1:1:1) to receive intravenous secukinumab 10 mg/kg (baseline, weeks 2 and 4) followed by subcutaneous secukinumab 150 mg or 75 mg every 4 weeks (starting from week 8) or placebo at the same dosing schedule.  The primary end-point was the ACR20 at week 24.  Other pre-defined hierarchical end-points included HAQ-DI, van der Heijde modified total Sharp score (vdH-mTSS) at week 24, and major clinical response (MCR; continuous 6 month period of ACR70 response) at 1 year.  The primary efficacy end-point was met with both secukinumab dose groups: ACR20 response rate at week 24 was 35.2 % for both secukinumab dose groups (p = 0.0009) versus 19.6 % for placebo.  The improvements in secondary end-points were greater in the secukinumab dose groups versus placebo but did not meet statistical significance.  The overall safety profile was similar across all treatment groups.  The authors concluded that this phase-III clinical trial was the only study of IL-17A inhibition on structural progression in RA.  While there may have been a numerical trend for inhibition of structural progression the trial was hampered by high discontinuation rates and a very short placebo period.  In contrast to the good efficacy of IL-17A inhibition seen in psoriasis, psoriatic arthritis and ankylosing spondylitis, secukinumab was of lesser benefit in RA patients for whom TNF-inhibitor therapy has failed.  These investigators stated that given that multiple biologics with good efficacy are already available to these patients, further development of secukinumab for RA patients was not pursued.

In a phase-III, double-blind, double-dummy, placebo-controlled trial, Dokoupilova and colleagues (2018) examined the safety and efficacy of secukinumab in patients with RA who failed to respond to TNF-α inhibitors.  This study randomized (1:1:1) patients to subcutaneous secukinumab 150 mg, secukinumab 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and then every 4 weeks; ACR 20 response at week 24 was the primary end-point.  Secondary outcomes included the 28-joint DAS28-CRP, HAQ-DI, and ACR50 at week 24.  Long-term treatment was planned for 5 years.  ACR20 response rates at week 24 for the secukinumab 150 mg and 75 mg groups were not statistically superior to placebo.  None of the secondary end-points was met for either secukinumab dose.  Although not statistically significant, compared with placebo, numerically greater differences in least squares mean changes from baseline in HAQ-DI score and numerically higher ACR50 response rates were observed at week 24 in both secukinumab treatment groups.  No new or unexpected adverse events (AEs) were observed in this study compared with the large secukinumab safety database across psoriasis, psoriatic arthritis, ankylosing spondylitis, and other RA studies.  The authors concluded that given that other 2nd-line therapies have demonstrated efficacy in RA patients who failed to respond to TNF-α inhibitors, these findings suggested that IL-17A inhibition with secukinumab did not provide additional benefit to these patients.  This study further confirmed the well-characterized safety profile of secukinumab.

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) Syndrome

Wendling and associates (2017) noted that SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare entity with skin and rheumatologic inflammatory presentation.  The treatment is not standardized, and in case of inadequate response to anti-inflammatory drugs, the use of anti-TNF or anti-IL-1 biologic treatments has been reported.  The IL-23/Th17 axis may be involved in SAPHO syndrome.  These investigators reported the results of 6 courses of IL-23 and IL-17 targeted therapies (3 ustekinumab and 3 secukinumab) in patients with SAPHO syndrome unresponsive to previous treatments (conventional synthetic DMARDs and biological DMARDs).  With a mean treatment duration of 5.5 months, improvement of skin symptoms was noticed in 3 cases, 1 improvement with secukinumab and 2 remissions (1 with secukinumab, 1 with ustekinumab).  Regarding the rheumatic symptoms, no major improvement was obvious under any of the 6 treatment courses.  No particular safety concerns were reported, except cases of paradoxical psoriasis flare in 1 under ustekinumab and the other case under secukinumab.  These preliminary findings need to be validated by well-designed studies.

Secukinumab Gene Therapy

Fallah and colleagues (2020) noted that TNF-α, checkpoint inhibitors, and IL-17 are critical targets in inflammation and autoimmune diseases.  Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases.  With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient's cells.  These researchers examined the results of an investigational assessment of secukinumab gene therapy.  In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector.  Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized.  After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy.  The engineered stem cells and recombinant viruses were applied for ex-vivo and in-vivo gene therapy, respectively, in different groups of rat models.  In-vitro and in-vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and ELISA by considering the approved secukinumab as the standard reference.  Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs.  Western blot and qRT-PCR confirmed in-vitro gene expression of secukinumab at both the mRNA and protein level.  ELISA testing of serum from treated rat models confirmed mAb over-expression for both in-vivo and ex-vivo gene therapies.  The authors concluded that in this study, a lentiviral-mediated ex-vivo and in-vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models.  These researchers stated that biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases.

Vitiligo

Speeckaert and colleagues (2019) noted that multiple reports confirmed elevated circulating IL-17 levels and increased numbers of Th17 lymphocytes in patients with non-segmental vitiligo.  Additionally, melanocyte damaging characteristics have been ascribed to IL-17.  In a single-arm, pilot study, these researchers examined the use of secukinumab in active non-segmental vitiligo.  The large majority of patients developed additional skin de-pigmentations limiting further enrollment.  Overall, laboratory analysis revealed no change in secreted chemokines or Th subsets.  Th17 lymphocytes correlated with Th2, Th9, and Th22 cells while an inverse link with Th1 cells and serum sCD25 levels was observed.  In contrast, Th17.1 cells correlated positively with Th1 lymphocytes.  Confirmatory results were found in an independent group of patients with vitiligo showing a significant increase in Th17.1 and Th1 lymphocytes in progressive vitiligo patients compared to healthy controls, which was not found for Th17 cells.  The authors concluded that these findings did not support a direct pathogenic role of IL-17 or Th17 cells in vitiligo.  Nonetheless, a delicate Th17/Th17.1/Th1 balance appeared evident that changed markedly according to disease activity.  This may offer new therapeutic options by interfering with cytokines that drive differentiation of Th17 cells toward Th1.

Appendix

Table: Brands of Targeted Immune Modulators and FDA-approved Indications
Brand Name Generic Name FDA Labeled Indications
Actemra tocilizumab

Giant cell arteritis

Juvenile idiopathic arthritis

Rheumatoid arthritis

Systemic juvenile idiopathic arthritis

Cytokine release syndrome (CRS)

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

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

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

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 Granulomatosis with polyangiitis

Microscopic polyangiitis

Pemphigus vulgaris

Rheumatoid arthritis
Siliq brodalumab Plaque psoriasis
Simponi golimumab

Ankylosing spondylitis

Psoriatic arthritis

Rheumatoid arthritis

Ulcerative colitis

Simponi Aria golimumab intravenous Ankylosing spondylitis

Psoriatic arthritis

Rheumatoid arthritis
Skyrizi risankizumab-rzaa Plaque psoriasis
Stelara ustekinumab

Crohn's disease

Plaque psoriasis

Psoriatic arthritis

Taltz ixekinumab

Ankylosing spondylitis

Plaque psoriasis

Psoriatic arthritis

Tremfya guselkumab

Plaque psoriasis

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:

86480 - 86481 Tuberculosis test, cell mediated immunity antigen response measurement
86580 Skin test; tuberculosis, intradermal
93635 - 93638 Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug)

HCPCS codes covered if selection criteria are met:

Secukinumab (Cosentyx) - no specific code:

HCPCS codes not covered for indications listed in the CPB:

Secukinumab Gene Therapy - no specific code:

Other HCPCS codes related to the CPB:

J0129 Injection, abatacept, 10 mg
J0135 Injection, adalimumab, 20 mg
J0717 Injection, certolizumab pegol 1 mg
J1438 Injection, etanercept, 25 mg
J1602 Injection, golimumab, 1 mg, for intravenous use
J1745 Injection, infliximab, 10 mg
J3245 Injection, tildrakizumab, 1 mg
J3262 Injection, Tocilizumab (Actemra), 1 mg
J3357 Injection, ustekinumab, 1 mg
J9312 Injection, rituximab, 10 mg
Q5109 Injection, infliximab-qbtx, biosimilar, (ixifi), 10 mg

ICD-10 codes covered if selection criteria are met:

L40.0 - L40.59, L40.9 Psoriasis [not covered for erythrodermic psoriasis]
M45.0 - M45.9 Ankylosing spondylitis

ICD-10 codes not covered for indications listed in the CPB:

A15.0 - A19.9 Tuberculosis
C22.0 Liver cell carcinoma
E10.10 - E10.9 Type 1 diabetes mellitus
G20 Parkinson's Disease
G30.0 - G30.9 Alzheimer's disease
H04.121 - H04.129 Dry eye syndrome
H20.041 - H20.049 Secondary noninfectious iridocyclitis
L20.0 - L20.9 Atopic dermatitis
L40.8 Other psoriasis [palmoplantar psoriasis]
L44.0 Pityriasis rubra pilaris
L57.5 Actinic granuloma
L63.0 - L63.9 Alopecia areata
L71.8 Other rosacea [papulopustular rosacea]
L73.2 Hidradenitis suppurativa
L80 Vitiligo
L88 Pyoderma gangrenosum
L92.0 Granuloma annulare
L92.9 Granulomatous disorder of the skin and subcutaneous tissue, unspecified [interstitial granulomatous dermatitis]
M05.00 - M05.9 Rheumatoid arthritis with rheumatoid factor
M35.2 Behcet's disease [uveitis]
M46.90 Unspecified inflammatory spondylopathy, site unspecified [non-radiographic axial spondyloarthritis]
M86.30 Chronic multifocal osteomyelitis, unspecified site [SAPHO]
N12 Tubulo-interstitial nephritis, not specified as acute or chronic [granulomatous interstitial nephritis]
Q80.0 Chronic multifocal osteomyelitis, unspecified site [SAPHO]
R76.11 Nonspecific reaction to tuberculin skin test without active tuberculosis

The above policy is based on the following references:

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