Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed.

Objective.To evaluate the 10-year drug survival of the first tumor necrosis factor inhibitor (TNFi) administered to patients with spondyloarthritis (SpA) overall and comparatively between SpA subsets, and to identify predictors of drug retention.Methods.Patients with SpA in the Hellenic Registry of Biologic Therapies, a prospective multicenter observational cohort, starting their first TNFi between 2004–2014 were analyzed. Kaplan-Meier curves and Cox regression models were used.Results.Overall, 404 out of 1077 patients (37.5%) discontinued treatment (followup: 4288 patient-yrs). Ten-year drug survival was 49%. In the unadjusted analyses, higher TNFi survival was observed in patients with ankylosing spondylitis (AS) compared to undifferentiated SpA and psoriatic arthritis [PsA; significant beyond the first 2.5 (p = 0.003) years and 7 years (p < 0.001), respectively], and in patients treated for isolated axial versus peripheral arthritis (p = 0.001). In all multivariable analyses, male sex was a predictor for longer TNFi survival. Use of methotrexate (MTX) was a predictor in PsA and in patients with peripheral arthritis. Absence of peripheral arthritis and use of a monoclonal antibody (as opposed to non-antibody TNFi) independently predicted longer TNFi survival in axial disease because of lower rates of inefficacy. Achievement of major responses during the first year in either axial or peripheral arthritis was the strongest predictor of longer therapy retention (HR 0.33, 95% CI 0.26–0.41 for Ankylosing Spondylitis Disease Activity Score inactive disease, and HR 0.35, 95% CI 0.24–0.50 for 28-joint Disease Activity Score remission).Conclusion.The longterm retention of the first TNFi administered to patients with SpA is high, especially for males with axial disease. The strongest predictor of longterm TNFi survival is a major response within the first year of treatment.

Objective To investigate whether tumour necrosis factor inhibitor (TNFi) combination therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is more effective for psoriatic arthritis (PsA) and/or improves TNFi drug survival compared to TNFi monotherapy. Methods Five PsA biologics cohorts were investigated between 2000 and 2015; the ATTRA registry (Czech Republic), the Swiss Clinical Quality Management PsA registry, the Hellenic Registry of Biologics Therapies (Greece), the University of Bari PsA biologics database (Italy) and the Bath PsA cohort (UK). Drug persistence was analysed using Kaplan-Meier and equality of survival using Log-Rank tests. Comparative effectiveness was investigated using logistic regression with propensity scores. Separate analyses were performed on: (a) the combined Italian/Swiss cohorts for change in rate of DAS-28; and (b) the combined Italian, Swiss and Bath cohorts for change in rate of HAQ. Results In total, 2294 patients were eligible for the drug survival analysis. In the Swiss (p=0.002), Greek (p=0.021) and Bath (p=0.014) databases patients starting TNFi in combination with MTX had longer drug survival compared to monotherapy, whilst in Italy the monotherapy group persisted longer (p=0.030). In patients from the combined Italian/Swiss dataset (n=1066) there was no significant difference between treatment arms in rate of change of DAS28. Similarly, when also including the Bath cohort (n=1205) there was no significant difference in rate of change of HAQ. Conclusion Combination therapy of a TNFi with a csDMARD does not appear to affect improvement of disease activity or HAQ versus TNFi monotherapy but may improve TNFi drug survival.

Background The long-term outcome of rheumatoid arthritis (RA) patients who in clinical practice exhibit persistent moderate disease activity (pMDA) despite treatment with biologics has not been adequately studied. Herein, we analyzed the 5-year outcome of the pMDA group and assessed for within-group heterogeneity. Methods We included longitudinally monitored RA patients from the Hellenic Registry of Biologic Therapies with persistent (cumulative time ≥ 50% of a 5-year period) moderate (pMDA, 3.2 < DAS28 ≤ 5.1) or remission/low (pRLDA, DAS28 ≤ 3.2) disease activity. The former was further classified into persistent lower-moderate (plMDA, DAS28 < 4.2) and higher-moderate (phMDA, DAS28 ≥ 4.2) subgroups. Five-year trajectories of functionality (HAQ) were the primary outcome in comparing pRLDA versus pMDA and assessing heterogeneity within the pMDA subgroups through multivariable mixed-effect regression. We further compared serious adverse events (SAEs) occurrence between the two groups. Results We identified 295 patients with pMDA and 90 patients with pRLDA, the former group comprising of plMDA (n = 133, 45%) and phMDA (n = 162, 55%). pMDA was associated with worse 5-year functionality trajectory than pRLDA (+ 0.27 HAQ units, CI 95% + 0.22 to + 0.33; p < 0.0001), while the phMDA subgroup had worse 5-year functionality than plMDA (+ 0.26 HAQ units, CI 95% 0.18 to 0.36; p < 0.0001). Importantly, higher persistent disease activity was associated with more SAEs [pRLDA: 0.2 ± 0.48 vs pMDA: 0.5 ± 0.96, p = 0.006; plMDA: 0.32 ± 0.6 vs phMDA: 0.64 ± 1.16, p = 0.038]. Male gender (p = 0.017), lower baseline DAS28 (p < 0.001), HAQ improvement > 0.22 (p = 0.029), and lower average DAS28 during the first trimester since treatment initiation (p = 0.001) independently predicted grouping into pRLDA. Conclusions In clinical practice, RA patients with pMDA while on bDMARDs have adverse long-term outcomes compared to lower disease activity status, while heterogeneity exists within the pMDA group in terms of 5-year functionality and SAEs. Targeted studies to better characterize pMDA subgroups are needed, in order to assist clinicians in tailoring treatments.

ObjectiveTo obtain real-world data on outcomes of belimumab treatment and respective prognostic factors in patients with systemic lupus erythematosus (SLE).MethodsObservational study of 188 active SLE patients (median disease duration 6.2 years, two previous immunosuppressive/biological agents) treated with belimumab, who were monitored for SLEDAI-2K, Physician Global Assessment (PGA), LLDAS (lupus low disease activity state), remission (DORIS/Padua definitions), SELENA-SLEDAI Flare Index, SLICC/ACR damage index and treatment discontinuations. Group-based disease activity trajectories were modelled followed by multinomial regression for predictive variables. Drug survival was analysed by Cox-regression.ResultsAt 6, 12 and 24 months, LLDAS was attained by 36.2%, 36.7% and 33.5%, DORIS-remission by 12.3%, 11.6% and 17.8%, and Padua-remission by 21.3%, 17.9% and 29.0%, respectively (attrition-corrected). Trajectory analysis of activity indices classified patients into complete (25.5%), partial (42.0%) and non-responder (32.4%) groups, which were predicted by baseline PGA, inflammatory rash, leukopenia and prior use of mycophenolate. During median follow-up of 15 months, efficacy-related discontinuations occurred in 31.4% of the cohort, especially in patients with higher baseline PGA (hazard ratio [HR] 2.78 per 1-unit; 95% CI 1.32-5.85). Conversely, PGA improvement at 3 months predicted longer drug retention (HR 0.57; 95% CI 0.33-0.97). Use of hydroxychloroquine was associated with lower risk for safety-related drug discontinuation (HR 0.33; 95% CI 0.13-0.85). Although severe flares were reduced, flares were not uncommon (58.0%) and contributed to treatment stops (odds ratio [OR] 1.73 per major flare; 95% CI 1.09-2.75) and damage accrual (OR 1.83 per mild/moderate flare; 95% CI 1.15-2.93).ConclusionsIn a real-life setting with predominant long-standing SLE, belimumab was effective in the majority of patients, facilitating the achievement of therapeutic targets. Monitoring PGA helps to identify patients who will likely benefit and stay on the treatment. Vigilance is required for the prevention and management of flares while on belimumab.

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BackgroundData regarding effectiveness and persistence to therapy with anti-IL17 agent secukinumab (SEC) in spondyloarthritis (SpA) patients of real world clinical practice are very limited.ObjectivesTo assess characteristics of SpA patients starting therapy with SEC versus tumor necrosis factor inhibitors (TNFis) in routine clinical care and compare clinical responses and treatment retention at 2 years.MethodsAll patients starting a bDMARD in the Rheumatology Department of the University Hospital of Heraklion, Crete, are included in a prospective observational study after their written informed consent. Data concerning disease activity at pre-specified time-points, drugs, comorbidities and any adverse events are recorded. For the present study we analyzed all consecutive patients with axial (AxSpA) or peripheral SpA (pSpA) starting or switching bDMARD therapy, either a TNFi or SEC from 1/2015 till 12/2018. We excluded patients with IBD-related SpA, patients starting ustekinumab (or apremilast) and patients switching from a bio-originator to a biosimilar TNFi. We compared disease activity scores improvement at 6 months using linear regression analysis and treatment retention using Kaplan-Meier survival curves with log-rank test and Cox regression. Inverse propensity score weighting (IPW) was used to adjust for the potential confounding of gender, age, disease duration, previous bDMARDs and csDMARDs number, diagnosis (AxSpA vs pSpA), presence of peripheral arthritis and co-therapy with csDMARDs.ResultsA total of 239 patients with SpA started/switched bDMARD (SEC:69, TNFis:170). SEC was the ≥3rd bDMARD in 63% of patients compared to 17% of TNFis (p<0.001). Patients’ characteristics at baseline were comparable except for disease duration (median (IQR): 5 (1.5-11) years in SEC vs. 0.9 (0.2-4.6) in TNFis, p<0.001). AxSpA was the diagnosis in 78% patients starting SEC and 79% starting TNFis while peripheral arthritis was slightly more common with SEC (81% vs 76% in TNFis). Monotherapy tended to be more common with SEC compared to TNFis (52% vs 42%, p=0.16). Baseline disease activity regarding both axial and peripheral arthritis was comparable in the two groups.Unadjusted 2-year treatment retention was similar in the two groups, both overall (SEC: 63%, TNFi: 56%, p=0.18) and due to failure or adverse events. However, when we selected only patients on 1st or 2nd bDMARD (SEC:26, TNFis:131), 2-year survival of SEC was higher than that of TNFis (95% vs. 57%, p=0.027). Similarly, SEC tended to have higher survival than TNFis in patients with pSpA (p=0.11). After IPW, SEC administration was an independent predictor for higher bDMARD retention overall [HR (95%CI)=0.48(0.33-0.69), p<0.001] and specifically due to discontinuation for failure [HR=0.58 (0.38-0.88), p=0.011] and for adverse events [HR=0.21 (0.08-0.62), p=0.004].Mean BASDAI and ASDAS improvements at 6 months were similar in patients with AxSpA receiving SEC or TNFis [Mean(SD) δBASDAI: 1.6 (2.5) vs 1.4(2.5) respectively (p=0.78) and δASDAS: 0.7 (1.4) vs 1.0 (1.5), p=0...

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort. Methods Sera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 < 3.2) and normal functionality (HAQ ≤ 0.25) while on treatment with conventional synthetic DMARDs and never used biologic DMARDs. Results We observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect −0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model. Conclusion Pending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.