Time until onset of action when treating psoriatic arthritis: meta-analysis and novel approach of generating confidence intervals

Psoriatic arthritis (PsA) is associated with progressive joint destruction and reduced quality of life. The time until a drug treatment starts to show an effect (TOA) is important for preventing joint destruction. The objective was to assess the time until onset of action of drugs when treating PsA. A systematic review of PsA drug trials was performed. Outcomes were: time until 25% of patients (TOA) reached (1) ≥ 20%, (2) ≥ 50% improvement in modified American College of Rheumatology response criteria (ACR), (3) ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75). 95% confidence intervals were calculated extracting data from graphs using a novel method. Meta-analysis was conducted. Two head-to-head trials show no difference between ixekizumab and adalimumab or adalimumab and tofacitinib for TOA-ACR outcomes. For PASI75, ixekizumab had a faster onset than adalimumab. Infliximab plus MTX was faster than MTX alone. Pooled results from 32 study arms for TOA-ACR20 (week [95% CI]) are: < 2 weeks: infliximab (1.18 [0.72-1.65]), ixekizumab (1.04 [0.80-1.28]), tofacitinib (10 mg 1.56 [1.14-1.98]); ≤ 4 weeks: adalimumab (1.95 [1.35-2.55]), secukinumab (75 mg 1.89 [0.16-3.62], 150 mg 2.13 [1.34-2.91], 300 mg 2.26 [1.75-2.76]), tofacitinib (5 mg 2.20 [1.41-2.99]); 4 + weeks: apremilast, ustekinumab. For TOA-ACR50, all pooled point estimates are > 4 weeks. For TOA-PASI75, the range is between 2.24 [1.65-2.84] for ixekizumab and 6.03 [3.76-8.29] for adalimumab. Indirect, mixed comparison suggest a faster onset of infliximab, ixekizumab and tofacitinib compared to apremilast, methotrexate and ustekinumab for ACR20, not ACR50. For PASI75, ixekizumab is faster than adalimumab.