AB0912 Swollen and tender joints improvement in the randomized controlled trials of psoriatic arthritis

Abstract

BackgroundThe ACR response is used to evaluate peripheral joints in psoriatic arthritis. However the main component in ACR treatment response is swollen (SJ) and tender joints (TJ), therewithal patient and physician global assessment, acute phase response, pain and function are included in this treatment response. Therefore, it can be thought that peripheral arthritis can best evaluated over SJ and TJ. Although ACR treatment responses are generally found to be similar between anti-TNF and anti-IL17/anti-IL23 in PsA, there is a general opinion that anti-TNF treatments may be more effective on the peripheral joint. (1).ObjectivesIn this study, it was aimed to evaluate the efficacy on SJ and TJ in RCTs performed in PsA.MethodsWe was searched with the keywords ‘psoriatric arthritis’ and ‘randomized controlled trial’ in Pubmed. All studies between 1975 and 31.10.2021 were screened for TJ count (SD) and SJ count (SD) values at treatment initiation and primary endpoint. The 2 studies with anti-TNFs and the SPIRIT-1 study comparing ixekizumab with placebo and adalimumab showed the number of SJ and TJ at baseline and primary endpoint. Effect size calculated separately according to Morris and Klauer formula. (2,3) We can interpret the effect size according to Cohen as follows: 0-0,1 no effect; 0,2-0,4 small effect; 0,5-0,7 intermediate effect; 0,8-≥1 large effect. (4)ResultsCertolizumab study, ES was found at a good level in the number of TJ and SJ at 200 and 400 mg doses. (ES 0.84 for SJ). The study comparing ixekizumab with adalimumab and placebo, it was observed that administration of ixekizumab every 4 weeks was minimally more effective in the number of TJ (ES 0.16) and SJ (ES 0.13) than adalimumab. The effect of ixekizumab over placebo is also slightly better than that of Adalimumab over placebo. (0.51 vs 0.36 in TJ, 0.38 vs 0.29 in SJ)Table 1.Effect size analysis of studiesTender Joint CountReferenceWeek (w)InterventionControlBaseline (Intervention vs Control)ES (Morris)ES (Klauer)Spirit-112Ixekizumab 4 w (n=107)Adalimumab (n=101)20,5 (13,7) vs 19,3 (13,0)0.160.9112Ixekizumab 2 w (n=103)Adalimumab (n=101)21,5 (14,1) vs 19,3 (13,0)0.120.2912Ixekizumab 4 w (n=107)Plasebo (n=106)20,5 (13,7) vs 19,2 (13,0)0.515.112Ixekizumab 2 w (n=103)Plasebo (n=106)21,5 (14,1) vs 19,2 (13,0)0.473.912Adalimumab (n=101)Plasebo (n=106)19,3 (13,0) vs 19,2 (13,0)0.364.1GENOVESE, Mark C., et al. M02-570 Study Group12Adalimumab (n=51)Plasebo (n=49)25,3 (18,3) vs 29,3 (18,1)0.190.30RAPID-PsA24Certolizumab 200 mg (n=138)Plasebo (n=136)21,5 (15,3) vs 19,9 (14,7)0.670.7524Certolizumab 400 mg (n=135)Plasebo (n=136)19,6 (14,8) vs 19,9 (14,7)0.490.61Swollen Joint CountSpirit-112Ixekizumab 4 w (n=107)Adalimumab (n=101)11.4 (8.2) vs 9.9 (6.5)0.130.6312Ixekizumab 2 w (n=103)Adalimumab (n=101)12,1 (7,2) vs 9,9 (4,7)0.191.1812Ixekizumab 4 w (n=107)Plasebo (n=106)11,4 (8,2) vs 10,6 (7,3)0.383.812Ixekizumab 2 w (n=103)Plasebo (n=106)12,1 (7,2) vs 10,6 (7,3)0.453.212Adalimumab (n=101)Plasebo (n=106)9.9 (6.5) vs 10.6 (7.3)0.294.4GENOVESE, Mark C., et al. M02-570 Study Group12Adalimumab (n=51)Plasebo (n=49)18.2 (10.9) vs 18.4 (12.1)0.330.29RAPID-PsA24Certolizumab 200 mg (n=138)Plasebo (n=136)11.0 (8.8) vs 11.0 (8.8)0.840.8324Certolizumab 400 mg (n=135)Plasebo (n=136)10.5 (7.5) vs 11.0 (8.8)0.840.87ConclusionChanges in the number of SJ and TJ that directly assess the peripheral joint have not been reported enough in RCTs in PsA patients. According to a limited number of reports, Anti-TNFs (eg, certolizumab) cause significant improvement in the number of SJ and TJ in the primary endpoint. On the other hand, Ixekizumab has as much effect on SJ and TJ as Adalimumab. The effect of anti-IL 17 treatments on the peripheral joint is not less than that of anti-TNFs, as thought.