Among patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) after open-label treatment with ixekizumab, continuing ixekizumab was superior to withdrawing treatment in maintaining low disease activity, according to study results published in Arthritis & Rheumatology. Researchers also noted that patients with PsA who had a relapse with treatment withdrawal re-achieved MDA on re-treatment.
Previous phase 3 trials with long-term extensions (SPIRIT-P1 and SPIRIT-P2) have shown that ixekizumab can improve signs and symptoms of active PsA. The objective of the current study was to determine the efficacy and safety of withdrawing vs continuing ixekizumab in patients who had achieved stable MDA with ixekizumab, and the effect of re-treatment after relapse.
The phase 3, multicenter study (SPIRIT-P3; ClinicalTrials.gov Identifier: NCT02584855) of biologic-naive adult patients with PsA from 12 countries, included an initial open-label treatment period followed by a randomized, double-blind withdrawal period. During the open-label phase, all patients received ixekizumab every 2 weeks for 36 weeks. Between week 36 and 64, patients who achieved sustained MDA were randomly assigned 1:1 to receive continued ixekizumab treatment or ixekizumab withdrawal (placebo) up to week 104. Patients who had not achieved MDA by week 64 continued to receive open-label ixekizumab up to week 104.
The primary efficacy endpoint was time to relapse, defined as a loss of MDA, during the randomized withdrawal period. Furthermore, the cumulative relapse rate and time to loss of response for each individual MDA component were assessed.
Investigators enrolled 394 patients (mean age, 47 years; 54% women) who received open-label ixekizumab every 2 weeks. A total of 291 (74%) patients completed the open-label treatment by week 36, including 158 (40%) who achieved sustained MDA. A total of 79 patients were randomly assigned to ixekizumab withdrawal and 79 to continued ixekizumab treatment. Overall, 133 patients who did not achieve sustained MDA were not included in the randomization and continued to receive open-label ixekizumab.
Cumulative relapse rate from week 24 to 104 was significantly higher for patients who were withdrawn from ixekizumab treatment compared with those who continued to receive ixekizumab (85% vs 38%, respectively; P <.0001). Median time to relapse was 22.3 weeks (95% CI, 16.1-28.3 weeks) for the ixekizumab withdrawal group; median time to relapse could not be reached for patients who continued to receive ixekizumab, as less than 50% experienced a relapse by the end of the study period (P <.0001).
When re-treated with ixekizumab following a relapse, 64 of 67 (96%) patients who had a relapse with treatment withdrawal re-achieved MDA on re-treatment. On re-treatment following relapse, median time to achieve MDA was 4.1 weeks (95% CI, 4.1-4.3 weeks) in the ixekizumab withdrawal/ixekizumab re-treatment group and 4.7 weeks (95% CI, 4.1-8.3 weeks) in the continued ixekizumab/re-treatment ixekizumab group.
Safety was consistent with the known safety profile of ixekizumab.
Study limitations included using an ixekizumab dosing regimen of every 2 weeks instead of the approved 4-week regimen for PsA, and the lack of assessment of dose reduction.
“These results indicate that continuous ixekizumab treatment is optimal for maintaining good disease control in PsA; however, patients can regain disease control after retreatment with ixekizumab in case of treatment interruption,” the researchers concluded.
Disclosures: This clinical trial was supported by Eli Lilly and Company. Please see the original reference for a full list of authors’ disclosures.
Coates LC, Pillai SG, Tahir H, et al. Withdrawing ixekizumab in patients with psoriatic arthritis who achieved minimal disease activity: results from a randomized, double-blind withdrawal study. Arthritis Rheumatol. Published online March 7, 2021. doi:10.1002/art.41716