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Objective Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavourable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi and biologic DMARDs (bDMARDs) in a large population of RA patients. Methods RA patients starting a new bDMARD or JAKi between 1 August 2018 and 31 January 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during the study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposure time and confounders. Results The number of unique patients included was 15 191, with 28 481 patient-years on treatment with either JAKi (2373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient-years) during therapy with JAKi and 383 events (1.47 events/100 patient-years) during therapy with bDMARDs, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% CI: 0.70, 1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. Conclusion In a large Dutch general RA population, the risk of cardiovascular events seems not to be different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded. [ABSTRACT FROM AUTHOR]

Objectives To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. Methods A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. Results In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). Conclusions The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs. [ABSTRACT FROM AUTHOR]

Objectives: To determine the effects of dose reduction of rituximab (RTX) on rheumatoid arthritis (RA) disease activity in clinical practice., Methods: Retrospective cohort study of RA patients using RTX, in stable low disease activity (i.e. Disease Activity Score 28-joint count CRP (DAS28-CRP) ≤3.5 for ≥6 consecutive months) and ≥2 DAS28-CRP measurements. We identified three treatment periods: 1) full dose RTX, 2) RTX dose reduction, and 3) stable RTX dose (and interval) after tapering. Linear mixed-model analysis was used to estimate mean DAS28-CRP during these periods. Rituximab use was assessed as the median percentage of the RTX Daily Defined Dose (%DDD) per period, with 1 x 1000 mg/6 months as reference., Results: 387 patients were included in the cohort with a median of 8 DAS28-CRP measurements (Q1-Q3:4-13) available per patient and median follow-up time of 44 months (Q1-Q3: 23-76). 299 patients tapered RTX and entered period 2 at least once, of whom 226 also entered period 3. Mean DAS28-CRP were 2.37 (95% CI: 2.29, 2.44) for period 1, 2.33 (95% CI: 2.25, 2.40) for period 2, and 2.27 (95% CI: 2.18, 2.35) for period 3, the latter significantly lower compared to period 1 (p=0.025). %DDD for the three time periods were 96%, 57% and 49%, respectively., Conclusions: Dose reduction of RTX in clinical practice is effective for many RA patients and leads to relevant dose reduction. Together with other previously proven benefits of ultra-low dose RTX, wider implementation of ultra-low dose RTX in RA patients should be considered.

The TREAT EARLIER was aimed at testing whether methotrexate could prevent the evolution from clinically suspect arthralgia to Rheumatoid Arthritis. Although the primary outcome was negative, symptoms did improve during and after use of methotrexate. Here we discuss how to interpret these findings, and place the study in the existing evidence.

Introduction: Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.