Publications

Burmester et al. provide insights into the benefit–risk profiles of UPA and adalimumab in patients with varying cardiovascular (CV) risks, suggesting that UPA may offer efficacy advantages over adalimumab irrespective of baseline CV risk, with generally similar rates of AEs. To better understand the benefits and risks of RA treatments in patients with different background CV risk, Burmester et al. assessed the short-term and long-term benefit–risk profiles of UPA and adalimumab in patients enrolled in SELECT-COMPARE.

Wollenhaupt et al. undertook a post-hoc analysis of data from eight Phase 3 and 3b/4 clinical trials to assess change from baseline (Δ) weight and BMI in patients with moderate to severe RA receiving TOF through 12 months. Additionally, Wollenhaupt et al. evaluated correlations between baseline/changes in disease activity, baseline CRP, and changes in lipids with Δweight and BMI. Wollenhaupt et al. showed that mean Δweight and BMI increased over time and were greater with TOF (all doses) versus placebo at Months 3 and 6, and with TOF monotherapy versus combination therapy, at Months 3, 6, and 12. The correlation and sensitivity analyses showed weak correlation between Δweight or BMI with TOF and DAS28-4(ESR), baseline CRP or lipid changes.

The SELECT-MONOTHERAPY study evaluated the safety and efficacy of UPA monotherapy through 260 weeks of treatment, in patients with RA who had prior inadequate response to MTX. No new safety signals were observed with long-term exposure to UPA, and results were consistent with prior findings and the established safety profile of UPA across indications. These data support the potential of UPA as a treatment option for patients with moderate to severe active RA who have responded inadequately to MTX.

Silvagni et al. aimed to comparatively assess the risk of cardiovascular events (CVE) in RA patients treated with JAKis or TNFis and to explore the interactions with patient profiles [including age, baseline cardio-cerebrovascular (CV) risk, and frailty, which is a state of decreased physiological reserve, assessed using a validated frailty index for Administrative Heathcare Databases (AHD)]. This AHD-based study highlighted no significantly increased risk of CVEs or MACEs for JAKis with respect to TNFis. The CV risk remains mainly driven by the patient profiles. The frailty, in parallel with baseline CV risk, emerged as an important determinant of CVEs, MACEs, and thromboembolic events (TEs). Frailty and baseline CV risk are key predictors of CVEs, MACEs, and TEs, and should be considered in both clinical assessment and trial design for RA patients on ts/b-DMARDs.

Phase 2 study data show that zimlovisertib + tofacitinib was more effective than tofacitinib alone, in patients with moderate-to-severe RA and an inadequate response to MTX.

Data from an international collaboration of registries show no evidence of an increase in CV events during the first 2 years of use with JAKi, compared to TNFi, in the general RA population.

Mariette et al. investigated the long-term safety of filgotinib with regard to MACE, VTE and malignancy across RA and UC clinical trial populations. Rates of these events remained low overall, with some increases observed in patients aged 65 years and older.

Kanda et al. investigated the efficacy of second-line b/tsDMARDs in RA patients unresponsive to first-line b/tsDMARDs. Using data from the FIRST registry, the study assessed 687 patients with RA treated with TNFis, IL-6 receptor inhibitors, cytotoxic T-lymphocyte-associated protein 4 immunoglobulin, or JAKis. After propensity score-based adjustment, JAKi showed the highest persistence rate, greatest improvement in CDAI, and highest remission rates at 24 weeks. Among JAKi, UPA was most effective in achieving remission, with a safety profile comparable to other b/tsDMARDs.

Eberhard et al. investigated the effectiveness of JAKi versus bDMARDs on pain reduction in RA patients, using Swedish national register data. JAKi treatment resulted in a significantly greater reduction in pain at three months compared with TNFis, with a higher proportion achieving low pain at 12 months, particularly in those previously treated with multiple bDMARDs.

Miyazaki et al. investigated the efficacy and safety of switching to bDMARDs versus cycling among JAKis in RA patients with inadequate JAKi response. Cycling to another JAKi proved more effective in improving disease activity at 26 weeks compared to switching to a bDMARD, and both groups had similar safety profiles.