Comparative effectiveness of cycling versus swapping to UL-17 inhibitors after first TNF inhibitor failure in Psoriatic Arthritis: A real- world multicenter study

he increase in biological disease-modifying antirheumatic drugs for psoriatic 153 arthritis (PsA) made it possible to consider different mechanisms of action (MoA) 154 after the failure of the first advanced-line therapy. However, there is still a lack 155 of real-world evidence comparing the cycling (re-administration of a similar MoA) 156 and the swap strategy. This retrospective observational study aims to evaluate 157 the retention rate, as a proxy for effectiveness, of second-line therapeutic 158 options after the failure of a TNF inhibitor (TNFi) by comparing cycling versus 159 swap strategies. 160 Methods 161 PsA patients who failed the first-line TNFi and subsequently received either a 162 TNFi or IL-17i were retrospectively selected from 25 centers. We collected 163 demographic and disease-related data (disease duration, clinical phenotype, 164 Disease Activity in Psoriatic Arthritis score), concomitant use of conventional 165 synthetic disease-modifying antirheumatic drugs. Patients were categorized into 166 cycling (second TNFi) (CG) or swapping (switch to IL-17i) (SG) groups. Kaplan- ARTICLE IN PRESS 167 Meier survival curves were used to evaluate the retention rate, and a Cox 168 regression analysis was performed to identify risk factors influencing treatment 169 retention. 170 Results 171 In CG and SG there were 275 and 177 patients, respectively. Retention rate in 172 SG was higher than in CG (p<0.001). Treatment interruption predictors were 173 cycling strategy (p<0.001), Disease Activity in Psoriatic Arthritis (p=0.013), 174 prescription year (p=0.016), axial (p=0.013), mixed involvement (p=0.001). 175 Conclusion 7 ACCEPTED MANUSCRIPT ARTICLE IN PRESS 176 The swap strategy showed higher treatment retention than cycling in PsA 177 patients who failed the first-line TNFi. This finding supports the hypothesis that 178 changing MoA may improve the chances of selecting the most effective PsA 179 treatment. 180 Clinical trial number: not applicable 181 182 Keywords 183 Psoriatic arthritis, TNFi, IL-17i, drug retention rate, bDMARDs, switch, cycling 184 strategy, swap strategy.