Search

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 Rituximab (RTX) is a safe and effective treatment for RA. However, there are some concerns about infection risk and preliminary data suggest dose and time dependency. This study aims to determine the infection incidence in a large real-life population of RA patients using RTX, with special focus on (ultra-)low dosing and time since last infusion. Methods RA patients treated with 1000, 500 or 200 mg RTX per cycle between 2012 and 2021 at the Sint Maartenskliniek were included in a retrospective cohort study. Patient-, disease-, treatment- and infection characteristics were retrieved from electronic health records. Infection incidence rates, dose and time relations with RTX infusion were analysed using mixed-effects Poisson regression. Results Among 490 patients, we identified 819 infections in 1254 patient years. Most infections were mild and respiratory tract infections were most common. Infection incidence rates were 41, 54 and 71 per 100 patient years for doses of 200, 500 and 1000 mg. Incidence rate ratio (IRR) was significantly lower for 200 mg compared with 1000 mg (adjusted IRR 0.35, 95% CI 0.17, 0.72, P  = 0.004). In patients receiving 1000 or 500 mg RTX, infections seemed to occur more frequently within the first two months after infusion compared with later on in the treatment cycle, suggesting an association with peak concentration. Conclusion Ultra-low dosing (200 mg) of RTX is associated with a lower risk of infections in RA. Future interventions focusing on ultra-low dosing and slow release of RTX (e.g. by subcutaneous administration) may lower infection risk. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a major contributor to pain and disability worldwide. Inflammation plays an important role in the development of osteoarthritis, and anti-inflammatory drugs may slow disease progression. This exploratory analysis of a randomized trial examined whether colchicine reduces incident total knee and hip replacements. Visual Abstract. Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements: Osteoarthritis is a major contributor to pain and disability worldwide. Inflammation plays an important role in the development of osteoarthritis, and anti-inflammatory drugs may slow disease progression. This exploratory analysis of a randomized trial examined whether colchicine reduces incident total knee and hip replacements. Background: Osteoarthritis is a major contributor to pain and disability worldwide. Given that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow disease progression. Objective: To examine whether colchicine, 0.5 mg daily, reduces incident total knee replacements (TKRs) and total hip replacements (THRs). Design: Exploratory analysis of the LoDoCo2 (Low-Dose Colchicine 2) randomized, controlled, double-blind trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000093684) Setting: 43 centers in Australia and the Netherlands. Patients: 5522 patients with chronic coronary artery disease. Intervention: Colchicine, 0.5 mg, or placebo once daily. Measurements: The primary outcome was time to first TKR or THR since randomization. All analyses were performed on an intention-to-treat basis. Results: A total of 2762 patients received colchicine and 2760 received placebo during a median follow-up of 28.6 months. During the trial, TKR or THR was performed in 68 patients (2.5%) in the colchicine group and 97 (3.5%) in the placebo group (incidence rate, 0.90 vs. 1.30 per 100 person-years; incidence rate difference, −0.40 [95% CI, −0.74 to −0.06] per 100 person-years; hazard ratio, 0.69 [CI, 0.51 to 0.95]). In sensitivity analyses, similar results were obtained when patients with gout at baseline were excluded and when joint replacements that occurred in the first 3 and 6 months of follow-up were omitted. Limitation: LoDoCo2 was not designed to investigate the effect of colchicine in osteoarthritis of the knee or hip and did not collect information specifically on osteoarthritis. Conclusion: In this exploratory analysis of the LoDoCo2 trial, use of colchicine, 0.5 mg daily, was associated with a lower incidence of TKR and THR. Further investigation of colchicine therapy to slow disease progression in osteoarthritis is warranted. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Objective: Systemic inflammation appears to contribute to the excess risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objective of this study was to investigate the effect of different levels of disease activity over time, particularly low disease activity and remission, on CVD risk in patients with RA.Methods: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events within the first 10 years of follow-up. Cut points of the DAS28 for remission (<2.6) and low (≤3.2), moderate (3.2-5.1) and high (>5.1) disease activity were used. The effect of disease activity on CVD risk was analysed using Cox-proportional hazards regression with DAS28 as a time-dependent covariate and also conventionally with time-averaged DAS28 as the primary dependent variable.Results: Low DAS28 (≤3.2) was significantly associated with a reduced risk of CVD (HR 0.65, 95% CI 0.43 to 0.99) compared with DAS28 >3.2, both when included as a time-dependent covariate and as time-averaged DAS28 ≤3.2 (HR 0.52, 95% CI 0.33 to 0.81). Remission had a modest, non-significant protective effect against CVD (HR 0.67, 95% CI 0.43 to 1.07).Conclusion: Results of this study suggest that low disease activity is sufficient to achieve a protective effect against CVD in RA. Apparently, remission defined as DAS28 <2.6 has no additional protective effect against CVD compared with low disease activity. Our results strengthen the use of tight control strategies in daily clinical practice to achieve low stable disease activity or remission in patients with RA as soon as possible. [ABSTRACT FROM AUTHOR]