Signs and symptoms of psoriatic arthritis (PsA) remained well controlled across multiple clinical domains in patients taking secukinumab for 104 weeks via subcutaneous injection, according to results from phase 3 of the FUTURE 2 study, published in Rheumatology. As the first large study to offer such evidence, FUTURE 2 presented encouraging data for both anti-tumor necrosis factor-alpha (TNFa)-naive and TNFa-IR subjects as to the extended safety, tolerability, and efficacy of secukinumab in the treatment of PsA.
When nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs fail to address patients’ needs, biologics such as TNF inhibitors and anti-interleukin-17A (IL-17Ai) antibodies are often useful for relieving signs and symptoms and offer patients better quality of life. However, TNF inhibitors are sometimes not well tolerated, with a subset of patients who respond poorly. Secukinumab, an immunoglobin G1 monoclonal antibody that neutralizes IL-17A, fills this clinical need by offering safe, effective, and rapid relief of immune-mediated conditions, including PsA.
The FUTURE 2 study (ClinicalTrials.gov identifier: NCT01752634) is an ongoing, randomized, double-blind, placebo-controlled study that sought to assess long-term efficacy, safety, and tolerability of secukinumab up to 104 weeks in active PsA. A total of 397 patients were randomly assigned into 4 treatment groups: secukinumab 300, 150, or 75 mg or placebo. The placebo group was re-randomized into secukinumab 300- or 150-mg treatment groups, at 16 weeks (nonresponders) or 24 weeks (responders). All randomizations were stratified by TNF inhibitor status. Of the 397 participants, 84% completed the study up to 52 weeks, with 76% still enrolled at 104 weeks. By treatment group, 86%, 76%, and 66% of subjects from the 300-, 150-, and 75-mg groups, respectively, finished the full 2 years.
The primary outcome was American College of Rheumatology 20% (ACR20) improvement response percentage, measured at 24, 52, and 104 weeks. Safety and tolerability was assessed by monitoring adverse events, laboratory findings, electrocardiogram findings, and vital signs.
By week 104, the secukinumab 300-, 150-, and 75-mg groups showed ACR20 response rates of 69.4%, 64.4%, and 50.3%, respectively. ACR50/70 proportions in the secukinumab 300-, 150-, and 75-mg groups were 50.6%/33.1%, 36%/23.1%, and 28.2%/14.9%, respectively. Psoriasis Area Severity Index 75%/90% improvement scores in secukinumab 300, 150, and 75 mg were 79.5%/69.6%, 73.3%/52.5%, and 58.4%/33.7%, respectively. Secukinumab was efficacious across a range of other clinical indicators vs placebo, including Disease Activity Score 28-joint count C reactive protein, Short Form-36 Physical Component Summary, Health Assessment Questionnaire-Disability Index, and resolution of enthesitis and dactylitis. Patient-reported outcomes improved by week 24, and this was sustained throughout.
The investigators reported good clinical responses for both TNF inhibitor -naive and TNF-inadequate responders although the latter group required higher doses of secukinumab to achieve such responses. Anti-TNFa-naive patients had ACR20 response rates at week 104 of 74.8%, 79.3%, and 62.7% with secukinumab 300, 150, and 75 mg, respectively. For TNFa-inadequate responders, the same measures after 2 years were 58.4%, 38.9%, and 26.3%, respectively. When divided by methotrexate (MTX) use, patients taking MTX concomitantly demonstrated ACR20 rates of 70.6%, 69.6%, and 54.1% with 300, 150, and 75 mg, respectively; the same rates in those not receiving MTX were 68.5%, 59.8%, and 45.8%, respectively.
Adverse events were reported as exposure-adjusted incidence rates per 100 patient-years, and adverse event types and rates were similar to those reported previously. The most common adverse events were infestations and infections. Over the course of 2 years, exposure-adjusted incidence rates were 163.3, 181.2, and 159.2 for those receiving 1 or more doses of secukinumab 300, 150, and 75 mg, respectively. In these same treatment groups, dropout rates secondary to adverse events were 3.4%, 5.6%, and 5.1%, respectively. Immunogenicity occurred in 3 subjects who developed anti-secukinumab antibodies, but without apparent effect on treatment success or adverse events. No dose-dependent relationship was established for adverse events, and there were no deaths reported during the study.
The authors note that TNF inhibitor-naive patients fared better than TNFa-inadequate responders overall. In addition, a dose of 300 mg generally achieved the most promising results, particularly in TNFa-inadequate responders. Concomitant MTX use did not significantly affect patient responses.
With demonstrated efficacy, safety, and tolerability, secukinumab appears to be an excellent alternative to TNFa therapies, particularly for those in whom TNFa medications present issues in terms of adverse events and loss of clinical response over time.
Mcinnes IB, Mease PJ, Ritchlin CT, et al. Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study [published online August 16, 2017]. Rheumatology. doi: 10.1093/rheumatology/kex301