Data from a phase 3 trial evaluating the efficacy of ixekizumab, an interleukin (IL)-17A-specific monoclonal antibody, in biologic-naive patients with active psoriatic arthritis (PsA) demonstrated that both physical function and disease activity are improved with treatment. IL-17A blockade also resulted in inhibition of the progression of structural joint damage, suggesting that IL-17A plays a key role in PsA pathogenesis. These results were recently published in the Annals of the Rheumatic Diseases.
The SPIRIT-P1 phase 3 trial (NCT01695239) was a multicenter, randomized, double-blind, placebo- and active comparator-controlled trial assessing the efficacy of ixekizumab in PsA. In this trial, adalimumab served as the active comparator.
The primary outcome evaluated in SPIRIT-P1 was the 24-week efficacy of ixekizumab as measured by American College of Rheumatology 20 Index (ACR20). Secondary outcomes measures included changes in modified Total Sharp Score (mTSS), proportion of patients achieving ACR50 and ACR70 responses, proportion of those achieving 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) score, 28-joint disease activity score using C-reactive protein (DAS28-CRP), and changes in Health Assessment Questionnaire-Disability Indices (HAQ-DI).
High Yield Data Summary
- Use of ixekizumab to block of IL-17A for 24 weeks resulted in reduced PsA disease activity as measured by DAS28-CRP in biologic-naive patients with active PsA
Patients eligible for study inclusion had an established diagnosis of PsA according to the Classification for Psoriatic Arthritis (CASPAR) criteria, with ≥3 of 68 tender joint count and ≥3 of 66 swollen joint count, evidence of at least 1 radiographic hand or foot joint erosion, or C-reactive protein > 6 mg/L.
Patients who had previously used or were currently taking a biologic disease-modifying antirheumatic drug (DMARD) for the treatment of either PsA or psoriasis were excluded from the study.
Patients maintained on stables doses of conventional DMARDs, oral corticosteroids, opiates, or nonsteroidal anti-inflammatory drugs were allowed to continue these concomitant medications throughout the study.
Study participants were randomly assigned to receive either ixekizumab 80 mg subcutaneous (SC) injection every 4 weeks (IXEQ4W, n=107), ixekizumab 80 mg SC injection every 2 weeks (IXEQ2W, n=103), adalimumab 40 mg SC injection every 2 weeks (active reference arm, n=101), or placebo SC injection (n=106) during the 24-week double-blind study period.
All patients receiving ixekizumab received initial loading doses of 160 mg. At 16 weeks post-randomization, patients receiving adalimumab or placebo designated as inadequate responders were re-randomized 1:1 to receive either IXEQ2W or IXEQ4W.
Follow-up visits to evaluate treatment safety and efficacy were scheduled at 1, 2, 4, 8, 12, 16, 20, and 24-weeks post-randomization. Radiographic imaging of both the hands and feet were obtained at screening, week 16, and week 24. At 24 weeks, the proportion of patients who achieved the primary outcome of achieving ACR20 was calculated based on intent-to-treat analyses.
A significantly greater proportion of patients randomly assigned to receive either IXEQ2W or IXEQ4W had achieved ACR20 at week 24 compared with those treated with placebo (P ≤.001). Patients in the adalimumab active reference group also had significantly greater ACR20 responses compared with placebo (P ≤.001).
At 24 weeks, PsA disease activity as measured by DAS28-CRP was also significantly reduced in patients receiving IXEQ4W, IXEQ2W, and adalimumab compared with placebo (all P ≤.001). Additionally, physical function at 24 weeks as measured by HAQ-DI was significantly improved from baseline in patients in all 3 treatment groups compared with placebo (all P ≤.001).
Progression of structural joint damage as measured by change in mTSS scores from baseline was also significantly reduced in patients in all 3 treatment groups compared with placebo (all P ≤.001). Improvements in plaque psoriasis were also noted in all 3 treatment groups.
Summary and Clinical Applicability
Specific blockade of IL-17A with ixekizumab (80 mg SC every 2 or 4 weeks) for 24 weeks resulted in reduced PsA disease activity and improvements in patient-reported functional outcomes in biologic-naive patients with active PsA.
Limitations and Disclosures
Long-term outcomes past 24 weeks have not yet been determined
Formal statistical comparison between outcomes with IXEQ2W And IXEQ4W was not performed
Generalizability of these results to patients with prior exposure to biologics, or those with disease that failed treatment with tumor necrosis factor (TNF) therapy, is currently being evaluated in the SPIRIT-P2 clinical trial (NCT02349295)
Mease PJ, van der Heijde DV, Ritchlin CT, et al; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2016 Aug 23. doi:10.1136/annrheumdis-2016-209709 [Epub ahead of print]