Continued ixekizumab therapy better than ixekizumab withdrawal in Psoriatic Arthritis patients

Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, has been demonstrated to improve the signs and symptoms of active PsA in two phases 3 trials with long-term extensions (SPIRIT-P1 and SPIRIT-P2). Recently, Dr Laura C. Coates and his team conducted a study to evaluate the effect of withdrawing ixekizumab in patients with psoriatic arthritis who had achieved minimal disease activity after open-label ixekizumab treatment.

SPIRIT-P3 was a multicenter, randomized, double-blind withdrawal study of 394 biologic-naive patients with PsA to open-label ixekizumab (160 mg at week 0, 80 mg every two weeks [IXE Q2W]) for 36 weeks. Among 394 patients, 158 patients achieved the sustained MDA for >3 consecutive months and were randomized to IXE Q2W withdrawal (placebo; n=79) or continued IXE Q2W treatment (n=79) for up to a week 104. The major outcome assessed was time to relapse (loss of MDA) for randomized patients. Patients who relapsed were retreated with IXE Q2W until week 104.

Perioperative systemic therapy:

Four 3-week neoadjuvant and adjuvant cycles of CAPOX (capecitabine and oxaliplatin), six 2-week neoadjuvant and adjuvant cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin), or six 2-week neoadjuvant cycles of FOLFIRI (fluorouracil, leucovorin, and irinotecan) and either four 3-week adjuvant cycles of capecitabine or six 2-week adjuvant cycles of fluorouracil with leucovorin. Bevacizumab was added to the first 3 (CAPOX) or 4 (FOLFOX/FOLFIRI) neoadjuvant cycles.

Key findings of the study were:

• During the median time of relapse by 22.3 weeks, the researchers noted that the patients relapsed more rapidly with treatment withdrawal than continued IXE Q2W treatment (67 (85%) patients vs 30 (38%) patients relapsed, respectively).
• On re-treatment following relapse, the median time to achieve MDA was 4.1 weeks in the ixekizumab withdrawal/ixekizumab re-treatment group and 4.7 weeks in the continued ixekizumab/re-treatment ixekizumab group.
• When re-treated with ixekizumab following a relapse, they noted 64 (96%) of 67 patients who relapsed with treatment withdrawal re-achieved MDA on retreatment.
• They also noted that the safety was consistent with the known safety profile for ixekizumab.

The authors concluded, "Continued ixekizumab therapy is superior to ixekizumab withdrawal in maintaining low disease activity in biologic-naive patients with PsA. Retreatment with ixekizumab following relapse may restore disease control in case of treatment interruption."

For further information:

https://onlinelibrary.wiley.com/doi/10.1002/art.41716