Publications

Schaefer et al. showed that treatment with JAKis (predominantly BARI and TOF) was associated with an increased HR of malignancies compared to treatment with bDMARDs in the overall study cohort, consistent with results from the ORAL surveillance trial. To better understand the complex role of JAKis in cancer development in RA patients, Schaefer et al. estimated the effects of JAKis compared to bDMARDs on the risk of malignancy (excluding NMSC) in patients with RA.

Wieczorek et al. present the first evidence supporting the use of a dual JAK and ROCK inhibitor as a potential treatment option for patients with RA who have inadequate response to MTX. Wieczorek et al. conducted a randomised, Phase 2 study of CPL’116 in patients with RA with inadequate response to MTX, to evaluate dose-dependent effects on disease control and pharmacokinetics, and its effect on laboratory abnormalities among other safety assessments.

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.

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.

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.

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.

Edwards et al. reported that in patients with RA who achieved sustained LDA or remission, tapering baricitinib from 4mg to 2mg allowed most to maintain LDA at 96 weeks. Rescue with 4mg restored control for the majority, demonstrating the feasibility of dose reduction with recovery potential for treatment.