Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.

BackgroundComedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy.MethodsPatients with PsA from 13 European countries who initiated a first TNFi in 2006–2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed.ResultsIn total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12–1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23–1.72)) and infliximab (OR 1.55 (1.21–1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept.ConclusionThis large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

Objective.To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017.Methods.Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models.Results.The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire–Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months.Conclusion.In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

BackgroundPatients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) under biologic treatment are increasingly achieving prolonged remission and tapering treatment is becoming standard practice. However, the optimal timing to start tapering remains unclear and predictors of loss of remission (LOR) are missing. Guidelines disagree on whether to wait for 6 or 12 months of sustained remission before tapering.ObjectivesTo determine whether longer sustained remission (6 versus 12 months) influences subsequent LOR rates and to identify predictors of LOR.MethodsWe used the Rheumatic Diseases Portuguese Register (Reuma.pt), to identify RA, PsA and axSpA patients on stable biologic treatment in a single center and retrospectively analyze those who achieved sustained remission for at least 6 and 12 months. Survival analysis was used to characterize stability of remission and identify predictors of LOR. The Cox proportional hazards regression was stratified by diagnosis and adjusted for age, gender, smoking, baseline disease activity, type of biologic, previous switches and starting year of biologic treatment.Results195 patients (100 RA, 51 PsA and 44 AxSpA) of 1078 patients (785 RA, 116 PsA, 177 axSpA) registered in Reuma.pt at a single center and treated with biologics between 1999 and 2018, had at least one remission period with a minimal duration of 6 months. This corresponded to 310 individual remission periods longer than 6 months, 232 of which (74.8%) were longer than 12 months. Median remission time (since the start of remission period) was 78.6 weeks overall vs. 99.0 weeks for patients with a minimum 12 months remission (difference in median survival: 20.4 weeks). PsA patients showed significantly longer remission periods (p<0.0001), followed by axSpA and RA. We identified active smoking (HR 1.96, p=0.008 for the total population; HR 1.53, p=0.20; HR 7.42, p=0.01, HR 0.74, p=0.79 for RA, PsA and axSpA, respectively), and infliximab use (HR 2.23, p=0.005 for the total population; HR 4.07, p<0.001, HR 3.20, p=0.36, HR 0.62, p=0.62 for RA, PsA and axSpA, respectively; subcutaneous TNF inhibitors (TNFi) used as index category) to be significantly associated with LOR. A sensitivity analysis excluding infliximab patients further suggested female gender (HR 3.21, p=0.005) and duration of disease until first biologic (HR 1.05, p=0.031) as important co-variates.Figure 1 – time to loss of remission considering a single flare (a) vs. persistent flare (b), all patients (minimum 150 days in remission). Number of failure events indicated in parenthesisFigure 2 – time to loss of remission considering a single flare (a) vs. persistent flare (b), only patients with minimum 320 days in remission. Number of failure events indicated in parenthesis.Figure 3 – time to loss of remission considering a single flare (a) vs. persistent flare (b) by diagnosis, all patients (minimum 150 days in remission).Conclusion6 vs. 12 months of sustained remission did not influence the subsequent rate of LOR. Sm...