POS0193 DAS28-CRP GUIDED TREAT-TO-TARGET TAPERING OF TUMOR NECROSIS FACTOR INHIBITORS IN PSORIATIC ARTHRITIS: A RETROSPECTIVE COHORT STUDY.
Authors: C. Michielsens, N. Den Broeder, M. Mulder, M. Wenink, F. Van den Hoogen, L. M. Verhoef, A. Den Broeder
Journal: Annals of the Rheumatic Diseases (2021)

Background: Tumor Necrosis Factor inhibitors (TNFi) have proven to be safe and effective in the treatment of psoriatic arthritis (PsA) [1]. However, they carry disadvantages, such as adverse effects, patient burden, and costs, which could be reduced by treat-to-target (T2T) tapering. Although there is lack of high level evidence, guidelines suggest that T2T tapering and discontinuation might be considered, but no studies comparing this strategy to continuation in PsA were published [2]. Objectives: To assess the effect of T2T TNFi tapering on disease activity and TNFi dosage in PsA patients with low disease activity (LDA). Methods: PsA patients using TNFi who visited the clinic between April 2012 and October 2018 were included if eligible for tapering, according to local protocol: ≥ 6 months of TNFi treatment and ≥ 6 months of at least LDA (DAS28-CRP &lt; 2.4 (or 2.9 in patients with disease duration &gt; 3 years) or by judgement of physician and patient). Patients with concomitant inflammatory disease preventing tapering were excluded. Three different time periods were defined: i) full-dose TNFi continuation; ii) TNFi tapering; iii) stable TNFi dosage after tapering. A mixed-model analysis was used to estimate mean DAS28-CRP during these three time periods. This model included: age, gender, disease duration, and the following time-varying components: current dose reduction status (three time periods mentioned above), time since eligibility for tapering and use of concomitant conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs), and a random intercept to account for inter-patient variability. Furthermore, a mean percentage of the Daily Defined Dose (%DDD) was calculated as secondary outcome. Results: 152 patients were included, with a mean of 6.5 DAS28-CRP measurements, of whom 125 attempted dose reduction during follow-up. Median follow-up duration was 41 months (Inter Quartile Range (IQR) 24-59) for patients who never attempted dose reduction and 43 months (IQR 28-58) for those who did (table 1). The mixed model showed no significant difference in DAS28-CRP between the three time periods. Adjusted for gender, age, disease duration at baseline, time since follow-up and csDMARD use, the mean DAS28-CRP was 1.91 in the continuation period (95% Confidence Interval (CI) [1.76-2.05]) and 2.0 in both the TNFi tapering (95%CI [1.90-2.12], difference with continuation: 0.11, p=0.19) and stable TNFi dosage after tapering (95%CI 1.88-2.11], difference with continuation: 0.09, p=0.31) period. The mean percentage of the DDD for the three time periods was 107% for the continuation period; 62% in the TNFi tapering period and 79% in the stable TNFi dosage period. Conclusion: T2T tapering of TNFi appears to have no negative effects on disease activity in PsA patients compared with full dose continuation, and reduces drug exposure. DAS28-CRP might however not capture the full disease spectrum in PsA. Trials using PsA specific endpoints are needed to investigate tapering in a prospective and randomized manner. References: [1]Gossec L. et al. Ann Rheum Dis. 2016;75(3):499-510. [2]Verhoef LM. et al. Cochrane Database Syst Rev. 2019;5:CD010455. Table 1. Baseline characteristics of PsA patients Characteristic PsA (N=152) Female, n (%) 60(39%) Age in years at inclusion, mean (SD) 52(11) Disease duration at inclusion, years, median (IQR) 9(3-14) Rheumatoid factor negative, n (%)* 132 (87%) Anti-CCP negative, n (%)** 136 (89%) Erosions on radiographic imaging, n (%) 34(22%) Number of previous bDMARD, n (%) -0 102(67%) -1 39(26%) -2 or 3 11(7%) Number of previous csDMARD, n (%) -0 21(14%) -1 50(33%) -≥ 2 81(53%) Current bDMARD use, n (%) -Adalimumab 49(32%) -Etanercept 81(53%) -Golimumab 3(2%) -Infliximab 19(13%) Current csDMARD use, n (%) -None 71(46%) -Methotrexate 65(43%) -Leflunomide 12(8%) -Hydroxychloroquine 1(1%) -Sulfasalazine 3 (2%) Duration of current bDMARD use at inclusion, years, median (IQR) 3(1-5) Duration of follow-up, months, median (IQR) 43(28-58) *Available for 144 of 152 patients ** Available for 145 of 152 patients Disclosure of Interests: Celia Michielsens: None declared, Nathan den Broeder: None declared, Michelle Mulder: None declared, Mark Wenink: None declared, Frank van den Hoogen Consultant of: Advisor board Abbvie and Galapagos, L.M. Verhoef: None declared, Alfons den Broeder Consultant of: received consultancy honoraria from Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: received research grants (to the institution) from Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead.