In a phase 3 study, ixekizumab showed significant, clinically meaningful improvements of disease activity and physical function for patients with psoriatic arthritis.
In a phase 3 study, ixekizumab showed significant, clinically meaningful improvements of disease activity and physical function for patients with psoriatic arthritis (PsA). The results of SPIRIT-P1 of Phase III study were presented in the 2015 Annual Meeting of American College of Rheumatology meeting in San Francisco this week.
PsA is a difficult clinical challenge that is associated with peripheral arthritis, enthesitis, and dactylitis, and is often resistant to treatment. Untreated, PsA often leads to chronic pain and, ultimately, joint damage.
Ixekizumab is an investigational IgG4 monoclonal antibody (developed by Eli Lilly and Co.) that binds with high affinity and specificity to the proinflammatory cytokine ILâ€‘17A. If ultimately approved by the Food and Drug Administration, Ixekizumab is a potential blockbuster.
In the current trial, 417 patients naive to biologic disease-modifying antirheumatic drugs (bDMARDs) and with active PsA were randomized to up to 24 weeks of placebo (N=106); adalimumab 40 mg (N=101) once every 2 weeks (Q2W; active control); or ixekizumab 80 mg Q2W (N=103) or Q4W (N=107) following 160 mg initial dose at Week 0. A total of 382 patients completed 24 weeks of the study.
A significantly greater percentage of patients treated with ixekizumab 80 mg Q2W or Q4W achieved ACR 20, ACR50, ACR70 and PASI 75/90/100 responses than with placebo at 12 and 24 weeks (p<.01).
Both ixekizumab groups experienced significantly greater reductions than placebo for measures of dactylitis (LDI-B) at 12 and 24 weeks but not for enthesitis (LEI). Disease activity (DAS28-CRP) and functional disability (HAQ-DI) improved and inhibition of radiographic progression of joint structural damage (mTSS) was demonstrated with both ixekizumab doses compared to placebo (p<.025).
Efficacy results with adalimumab versus placebo were significant on most measures, thus validating the study design. At 24 weeks, the incidence of treatment-emergent adverse events (TEAE) was greater (p<.05) and the rate of serious adverse events was higher (p>.27) with ixekizumab and adalimumab compared to placebo. Discontinuation due to a TEAE was similar across groups.
During treatment, the drug showed more significant results compared with placebo that resulted PsA patients having significantly less progression of radiographic structural joint damage, improved skin clearance of plaque psoriasis, and reduced disability when performing certain physical functions.
Other key secondary measures were assessed by using the Health Assessment Questionnaire Disability Index (HAQ-DI). The improved skin clearance of plaque psoriasis was measured by the Psoriasis Area and Severity Index (PASI), including PASI75, 90, and 100.
The scores of PASI75 specify at least a 75% reduction in a patient's plaque psoriasis from their baseline assessment. The PASI90 reflects a 90% fall and PASI100 represents a 100% decrease resulted complete skin clearance.