Phase 3 data from the SPIRIT-P1 study showed the new interleukin 17A (IL-17A) inhibitor ixekizumab to be safe and effective for treating psoriatic arthritis (PsA). The findings put the monoclonal on track to join another IL-17A antibody, secukinumab, as PsA therapy, and further highlight the importance of IL-17A as a therapeutic target in psoriasis.
However, the study enrolled only patients with PsA not previously treated with biologics, such as tumor necrosis factor alpha inhibitors, which are already widely used in psoriasis treatment. Thus, the researchers warn that the findings might not be generalizable to patients who have failed prior biologic therapy. They note that the ongoing SPIRIT-P2 trial tests the drug's efficacy in that patient group.
Philip J. Mease, MD, from the Department of Rheumatology, Swedish Medical Center, and University of Washington, Seattle, Washington, and colleagues report the results of the company-funded study in an article published online August 23 in the Annals of the Rheumatic Diseases.
Patients in the four-group study were randomly assigned to subcutaneous injections of placebo (n=106), ixekizumab 80 mg once every 2 weeks (IXEQ2W, n=103), ixekizumab 80 mg every 4 weeks (IXWQ4W, n=107), or adalimumab 40 mg every 2 weeks (n=101). Both ixekizumab groups received 160-mg starting doses. Groups were similar at baseline, with the exception that those in the adalimumab group were significantly heavier (91.6 vs 81.6 - 85.5 kg for the other three groups).
The study's primary objective was to test the efficacy of the 2 ixekizumab doses vs placebo. The study was not powered to assess equivalence or noninferiority of ixekizumab vs adalimumab, which was included as an "active reference arm," the authors explain.
At week 25, American College of Rheumatology (ACR) 20 response rates, which was the primary endpoint, were 57.9% for the IXEQ4W group (P ≤ .001 vs placebo) and 62.1% for IXEQ2W (P ≤ .001 vs placebo). ACR20 for the adalimumab reference group was 57.4% (P ≤ .001 vs placebo).
Furthermore, response was very quick, the authors report. "ACR20 response rates for both ixekizumab groups and the adalimumab group were significantly greater than the placebo group as early as week 1 (p≤0.01), and the differences were maintained throughout the 24-week period (p≤0.01)."
ACR 50 and ACR 70 were similarly better with ixekizumab than with placebo and were also maintained to 24 weeks, as were reductions in 28-Joint Disease Activity Score Using C-Reactive Protein, improvements in physical function, and reduction in the progression of radiographically apparent structural damage.
"Significantly greater percentages of patients in the ixekizumab groups and adalimumab group at week 24 experienced no structural progression [in the van der Heijde modified total Sharp score,] as defined by thresholds of ≤0.5 or ≤0.95 compared with the placebo group," the researchers write.
More patients in the ixekizumab (66%) and adalimumab (64%) groups had treatment-related adverse events than in the placebo group (47.2%). These were most commonly injection site reactions, injection site erythema, or nasopharyngitis, and were typically mild or moderate.
The authors report, "In this phase III study, 80 mg of ixekizumab administered every 2 weeks or 4 weeks after a starting dose of 160 mg significantly improved signs and symptoms, including enthesitis and dactylitis, of PsA and patient-reported physical functioning, while also inhibiting bone destruction. Both ixekizumab dose regimens significantly reduced radiographic progression of joint damage when compared with placebo. A rapid therapeutic response was apparent as early as 1 week after beginning therapy. Moreover, nearly half of the patients with ≥3% affected [body surface area] who were treated with ixekizumab achieved complete clearance of their psoriasis."
Steven Daveluy, MD, assistant professor of dermatology, Wayne State University, Dearborn, Michigan, told Medscape Medical News, "I think the study was very well designed. Their primary endpoint alone demonstrated the efficacy of ixekizumab in psoriatic arthritis. Beyond the ACR20, they utilized many different outcome measures that corroborated their findings, strengthening the results. Ixekizumab has already been studied in psoriasis of the skin, and the safety findings were consistent with those results." Dr Daveluy was not involved in this study.
Arthur Kavanaugh, MD, professor of medicine and director, Center for Innovative Therapy, University of California, San Diego, told Medscape Medical News, "I think it is a very good study. Along with prior data with secukinumab, this establishes IL-17 as a viable target across domains of PsA. It is a good thing in studies in rheumatology to have comparators, so the inclusion of adalimumab is good from that standpoint." Dr Kavanaugh noted that, as the researchers point out, statistically valid comparisons of the active treatment groups were not possible, but both therapies were effective. Dr Kavanaugh was not involved in the study.
Dr Daveluy added, "I think the adalimumab arm of the study is beneficial to the study, but it also creates the potential for some confusion. As mentioned, the study isn't powered to compare equivalence or noninferiority, but comparing the efficacy of various treatments for psoriatic arthritis is of great interest to clinicians, especially as more treatments become available. While the clinical trials involving different treatments often utilize the same outcome measures, the results can't be directly compared since the clinical trial protocols vary between studies. This creates the need for more head-to-head trials to provide clinicians with further information to drive their clinical decisions."
The study was funded and sponsored by Eli Lilly and Company. Dr Mease received grants and personal fees from Eli Lilly & Company during the conduct of the study, as well as grants, personal fees, and nonfinancial support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Pfizer, and UCB Pharma; grants and personal fees from Merck and Novartis; and nonfinancial support from Corrona. Two coauthors were employees of Eli Lilly & Company at the time this study was conducted. Three coauthors are employees of Eli Lilly & Company. Other coauthors received personal fees or other support from Eli Lilly & Company and other pharmaceutical companies. Dr Kavanaugh has conducted clinical trials supported by Eli Lilly & Company. Dr Daveluy has disclosed no relevant financial relationships.
Ann Rheum Dis. Published online August 23, 2016. Full text
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Cite this: Ixekizumab Effective in Phase 3 Psoriatic Arthritis Trial - Medscape - Sep 08, 2016.