Efficacy and safety of Janus kinase inhibitors in patients with difficult-to-treat rheumatoid arthritis.

This study evaluated the effectiveness of Janus kinase inhibitors (JAKi) in patients with difficult-to-treat rheumatoid arthritis (D2T RA). This study included 220 patients with RA who were treated with JAKi. Sixty-two patients were naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs)/JAKi (1st group), 57 patients were failure to one bDMARDs/JAKi (2nd group), and 101 patients were failure to ≥ 2 bDMARDs/JAKi. Of these 101 patients, 25 did not meet the D2T RA criteria (non-D2T RA group) and 76 met the D2T RA criteria (D2T RA group). : DAS28-ESR was improved in all groups at 24 weeks (1st: p<0.01, 2nd: p<0.01, non-D2T RA: p=0.01, D2TRA: p=0.02), and improvement ratio of DAS28-ESR was not different between DT2RA group and 2nd (p=0.73) or non-D2T RA group (p=0.68). Glucocorticoid use (odds ratios: 8.67; 95% CI: 1.23-60.90; P=0.03) and number of past bDMARD/JAKi uses ≥ 3 (odds ratios: 10.55; 95% CI: 1.39-80.30; P=0.02) were risk factors for DAS28-ESR ≥ 3.2 at 24 weeks in the D2T RA group. Clinical efficacy of JAKi in D2T RA group did not differ from that in 2nd and non-D2T RA groups. Glucocorticoid use and multiple bDMARD/JAKi failure were poor prognostic factors for D2T RA.

Anno S ，Okano T ，Mamoto K ，Yamada Y ，Mandai K ，Orita K ，Iida T ，Tada M ，Inui K ，Koike T ，Nakamura H ... -  《-》

Is Baricitinib Effective and Safe for Patients with Difficult-to-Treat Rheumatoid Arthritis? Comparative Data with the Rheumatoid Arthritis Group of Rheumatoid Arthritis Not Difficult to Treat.

This study investigates the efficacy and safety of baricitinib, an oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs), in patients with difficult-to-treat rheumatoid arthritis (D2T RA) compared to those without, aiming to determine its potential as an alternative treatment for D2T RA. A total of 78 patients participated in this retrospective cohort study, with 33 meeting the D2T RA criteria and 45 in the non-D2T RA group. Various clinical and laboratory parameters, adverse events, and disease activity indices were assessed, alongside drug efficacy and survival rates. Patients with D2T RA exhibited higher seronegativity, prior use of b-DMARDs and c-DMARDs, and longer disease duration. Both groups experienced reductions in VAS and DAS28 scores, as well as SDAI, CDAI, HAQ, CRP, and ESR levels at baseline and 3, 6, and 12 months post-baricitinib initiation, with sustained efficacy observed over 12 months. The most prevalent adverse event was infection (28.21%). Although initial drug survival rates were similar between groups, the non-D2T RA group demonstrated higher rates at 24 months (46.70% vs. 59.40%). Subgroup analyses showed comparable survival rates between D2T RA and non-D2T RA groups, whether treated with baricitinib alone or in combination with methotrexate or leflunomide. Despite potential treatment resistance, patients meeting the D2T RA criteria shared similar safety and efficacy profiles with those non-D2T RA. Baricitinib emerges as a promising treatment option for D2T RA patients, offering effectiveness and safety comparable to the non-D2T RA group. This study investigates the efficacy and safety of baricitinib, an oral targeted synthetic disease-modifying antirheumatic drugs (DMARDs), in patients with difficult-to-treat rheumatoid arthritis (D2T RA) compared to those without, aiming to determine its potential as an alternative treatment for D2T RA. A total of 78 patients participated in this retrospective cohort study, with 33 meeting the D2T RA criteria and 45 in the non-D2T RA group. Various clinical and laboratory parameters, adverse events, and disease activity indices were assessed, alongside drug efficacy and survival rates. Patients with D2T RA exhibited higher seronegativity, prior use of b-DMARDs and c-DMARDs, and longer disease duration. Both groups experienced reductions in VAS and DAS28 scores, as well as SDAI, CDAI, HAQ, CRP, and ESR levels at baseline and 3, 6, and 12 months post-baricitinib initiation, with sustained efficacy observed over 12 months. The most prevalent adverse event was infection (28.21%). Although initial drug survival rates were similar between groups, the non-D2T RA group demonstrated higher rates at 24 months (46.70% vs. 59.40%). Subgroup analyses showed comparable survival rates between D2T RA and non-D2T RA groups, whether treated with baricitinib alone or in combination with methotrexate or leflunomide. Despite potential treatment resistance, patients meeting the D2T RA criteria shared similar safety and efficacy profiles with those non-D2T RA. Baricitinib emerges as a promising treatment option for D2T RA patients, offering effectiveness and safety comparable to the non-D2T RA group.

Ekin A ，Misirci S ，Görünen A ，Coskun BN ，Yagiz B ，Dalkilic E ，Pehlivan Y ... -  《-》

Real-world assessment of the efficacy and tolerability profile of JAK inhibitors in difficult-to-treat rheumatoid arthritis.

To evaluate the effectiveness and tolerability of JAK inhibitors (JAKi) in patients with difficult-to-treat rheumatoid arthritis (D2TRA) in clinical practice. We included RA patients initiating a JAKi between 2018 and 2022. Patients meeting EULAR criteria for D2TRA were compared to active non-D2TRA patients. Efficacy was evaluated at the first visit (FV) (6 months following JAKi initiation) and the last available visit (LV) up to December 2022. 45 patients with D2TRA, all presenting signs of disease activity (imaging, CRP levels), were compared to 29 active non-D2TRA. DAS28 and DAS28-CRP reduction from baseline to FV was significant and similar between both groups, before and after adjusting for several factors including the number and exposure duration to previous targeted therapies. DAS28 and DAS28-CRP remained stable in both groups between FV and LV. The proportion of responders and patients achieving remission or low disease activity at FV and LV was similar in both groups. Thirty-five patients (42 %) discontinued JAKi over a mean observation period of 20±10 months, with no significant difference in discontinuation rates between groups (p = 0.36). Discontinuations due to inefficacy and side effects were evenly distributed. Frequency of infections, herpes zoster, myocardial infarctions, and venous thromboembolism was similar between groups, with a higher likelihood in patients aged ≥65 years and/or with at least one cardiovascular risk factor (30/39, 77 %). JAKi effectively reduced disease activity in D2TRA patients with the same extent as active non-D2TRA patients. Tolerability profiles were comparable, with outcomes largely dependent on the presence of age and/or cardiovascular risk factors. Haut du formulaire.

Al Tabaa O ，Hecquet S ，Thomas M ，Carvès S ，Combier A ，Miceli-Richard C ，Molto A ，Fogel O ，Allanore Y ，Avouac J ... -  《-》

Switching to biological DMARDs versus cycling among JAK inhibitors in patients with rheumatoid arthritis and with inadequate response to JAK inhibitors: from FIRST registry.

This study aimed to identify characteristics of patients with rheumatoid arthritis (RA) with an inadequate response to Janus kinase inhibitors (JAKi-IR) and evaluate the efficacy and safety of subsequent treatments. This study included 434 patients with RA who started JAKi treatment. JAKi-IR patients were those who switched to another drug due to inadequate response or did not reach low disease activity within 26 weeks of beginning JAKi. The efficacy and safety of switched biological disease-modifying anti-rheumatic drugs (bDMARDs) or cycled targeted synthetic disease-modifying anti-rheumatic drugs were analysed 26 weeks after switching treatment in JAKi-IR patients. Patients with JAKi-IR RA accounted for 31.8% (n=138/434). Multiple logistic regression identified factors contributing to JAKi-IR, such as the prior use of multiple ineffective bDMARDs and suboptimal JAKi dosing. There were no differences in patient background when comparing patients with RA with JAKi-IR who cycled to another JAKi (n=31) versus those who switched to bDMARDs (n=45). Among those cycling to another JAKi, the Clinical Disease Activity Index (CDAI) scores improved by week 26, with higher remission rates, while retention and adverse events remained similar. Trajectory analysis identified three CDAI response patterns, with the 'treatment response' group showing rapid and sustained improvement when cycling to another JAKi. Multiple logistic regression in this group identified another JAKi cycle as the critical factor for the treatment response. Cycling JAKis is more effective than switching to bDMARDs in JAKi-IR RA, with no differences in safety or retention. This study suggests that cycling to another JAKi may be appropriate for patients with RA with JAKi-IR.

Miyazaki Y ，Nakayamada S ，Tanaka H ，Hanami K ，Fukuyo S ，Kubo S ，Yamaguchi A ，Miyagawa I ，Satoh-Kanda Y ，Todoroki Y ，Inoue Y ，Ueno M ，Tanaka Y ... -  《-》

Retention rates of different Janus kinase inhibitors in rheumatoid arthritis: experience from a large monocentric cohort.

Farina N ，Tomelleri A ，Boffini N ，Cariddi A ，Calvisi S ，Viapiana N ，Baldissera E ，Matucci-Cerinic M ，Dagna L ... -  《-》