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Objectives: To describe safety and efficacy of filgotinib 200 or 100 mg (FIL200/FIL100) in Japanese patients with rheumatoid arthritis in a long-term extension (LTE; NCT03025308)., Methods: Patients who completed any of three parent studies (NCT02889796: inadequate response [IR] to methotrexate [MTX]; NCT02873936: IR to biologic disease-modifying antirheumatic drugs; NCT02886728: MTX-naïve) without rescue therapy could enter the LTE; patients taking FIL continued their dosage, and those who received comparators were rerandomised to FIL200 or FIL100. This analysis includes week 156 interim results., Results: Among Japanese patients, 110 received FIL200, and 97 received FIL100. Mean (SD) FIL200 and FIL100 exposure was 157.0 (51.49) and 156.0 (52.45) weeks. The exposure-adjusted incidence rates (95% CI) for FIL200/FIL100 were 2.7 (1.4, 5.2)/2.4 (1.2, 5.1) for herpes zoster, 0.9 (0.3, 2.8)/1.0 (0.3, 3.2) for malignancy (excluding nonmelanoma skin cancer), and 0.6 (0.2, 2.4)/0.3 (0.0, 2.4) for major adverse cardiovascular events. More patients receiving FIL200 with prior FIL200 exposure achieved clinical remission vs other groups (including Clinical Disease Activity Index remission in 40% vs 27% or less at week 156)., Conclusions: FIL200 and FIL100 were generally well tolerated by Japanese patients, without new, unexpected adverse events., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Janus kinase inhibitors are an effective option for achieving sustained remission or low disease activity in patients with rheumatoid arthritis (RA) following inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Filgotinib is a Janus kinase 1-preferential inhibitor available in two doses for moderate-to-severe RA. We report the long-term efficacy and safety of filgotinib., Methods: In the ongoing long-term extension study FINCH 4 (NCT03025308), patients continue filgotinib 200 mg or 100 mg from FINCH 1, 2 or 3 or receive filgotinib 200 mg or 100 mg de novo. Efficacy assessments up to week 156 include American College of Rheumatology 20% response (ACR20), Disease Activity Score 28 using C-reactive protein of <2.6, Clinical Disease Activity Index of ≤2.8, Simplified Disease Activity Index of ≤3.3 and Boolean remission (1.0 and 2.0) with non-responder imputation., Results: In patients with an inadequate response to methotrexate, 60.2% and 54.6% receiving de novo filgotinib 200 mg and 100 mg had an ACR20 at week 156, respectively, as did 67.3% and 59.5% of those who continued filgotinib 200 mg and 100 mg. At week 156, Boolean remission 1.0 was achieved by 18.8% and 15.4% of patients treated with de novo filgotinib 200 mg and 100 mg, respectively, and by 21.1% and 18.5% when Boolean 2.0 criteria were applied. Similar efficacy data were seen in patients from FINCH 2 and 3. Safety data were consistent with the known safety profile of filgotinib., Conclusion: In FINCH 4, filgotinib 200 mg and 100 mg (continuous or de novo) demonstrated sustained efficacy up to week 156 in patients enrolled from FINCH 1, 2 or 3, with no unexpected safety results., Competing Interests: Competing interests: MHB reports consultancy fees from AbbVie, Boehringer Ingelheim, CESAS Medical, Galapagos, Gilead and Pfizer (all paid to host institution); speaker fees from AbbVie (paid to host institution); and grant/research support from Gilead (paid to host institution). DA reports consultancy fees, speaker fees and grant/research support from AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Sandoz and Sanofi. BGC reports consultancy fees from AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Janssen and Roche-Chugai; and speaker fees from AbbVie, Celltrion, Eli Lilly, Galapagos, Janssen, Pfizer and Roche-Chugai. YT reports speaker fees and/or honoraria from AbbVie, Asahi Kasei, AstraZeneca, Boehringer Ingelheim, BMS, Chugai, Eli Lilly, Eisai, Gilead, GSK, Pfizer, Taisho and Taiho; and research grants from Asahi Kasei, Chugai, Eisai, Mitsubishi Tanabe and Taisho. RC reports consultancy fees from AbbVie, Accord, Eli Lilly, Fresenius Kabi, Galapagos, MSD, Novartis, Pfizer and UCB; and speaker fees from AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer and UCB. HS-K reports consultancy fees and speaker fees from AbbVie, Eli Lilly, Galapagos and Pfizer. TT reports consultancy fees from AbbVie, Astellas Pharma, Eli Lilly Japan and Gilead; and speaker fees and/or honoraria from AbbVie, Astellas Pharma, Eisai, Eli Lilly Japan, Gilead and Pfizer Japan. J-EG reports consultancy fees from AbbVie, BMS, Eli Lilly, Galapagos, Gilead, MSD, Novartis and Pfizer; and grant/research support from AbbVie, BMS, Lilly and Pfizer. RB reports consultancy fees from AstraZeneca, Galapagos, Janssen, Novartis and Pfizer; speaker fees from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche and Sanofi; and grant/research support from AbbVie and Roche. PV reports consultancy fees from Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma and Sidekick Health; speaker fees from AbbVie, Eli Lilly, Galapagos and Roularta; and grant/research support from Galapagos and Pfizer. AZ-S has no disclosures of interest to report. FDL is a former employee of, and shareholder in, Galapagos. EVEO reports consultancy fees from Galapagos and Janssen and is a shareholder in UCB. VR is a former employee of Galapagos and current employee of GSK Vaccines. PE reports consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead and Novartis; speaker fees from AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, Novartis and Samsung; and grant/research support from AbbVie, BMS, Eli Lilly and Samsung., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Filgotinib is an oral preferential Janus kinase 1 inhibitor that demonstrated significant reductions in radiographic progression, with an acceptable tolerability and safety profile, vs placebo in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR; FINCH 1) and vs MTX in MTX-naïve patients with RA (FINCH 3). International treatment guidelines identify multiple poor prognostic factors (PPFs) associated with worse disease outcomes among patients with RA. However, questions remain both about the clinical utility of considering PPFs and about which PPFs should drive treatment decisions. Additionally, the role of radiographic findings in clinical practice continues to be discussed and to evolve. This review examines radiographic results from post hoc analyses of phase 3 trials of filgotinib that examined subgroups with 4 PPFs or with baseline estimated rapid radiographic progression (e-RRP). In MTX groups, there were trends toward greater progression among patients with 4 PPFs or e-RRP, suggesting these subgroups may comprise a higher-risk population. Results show general consistency for the efficacy of filgotinib 200 mg plus MTX vs placebo plus MTX/MTX monotherapy on radiographic assessments, including change from baseline in modified total Sharp score and proportions without radiographic progression, even among MTX-IR or MTX-naïve patients with 4 PPFs or e-RRP who may be at higher risk of bone damage. Multivariate analysis identified multiple factors associated with baseline e-RRP status. This summary of the current understanding of benefits associated with filgotinib on radiographic progression and the relevance of baseline factors to these benefits may help inform treatment decisions for patients facing high risk of radiographic progression., (© 2023. The Author(s).)

Objectives: To present safety and efficacy of the JAK1 preferential inhibitor filgotinib in Japanese patients with prior inadequate response (IR) to methotrexate (MTX) from a 52-week randomised controlled parent study (PS) and long-term extension (LTE) through June 2020., Methods: The PS (NCT02889796) randomised MTX-IR patients to filgotinib 200 (FIL200) or 100 mg (FIL100), adalimumab (ADA) 40 mg, or placebo; all took stable background MTX. At week (W) 24, placebo patients were rerandomised to FIL200 or FIL100. The primary endpoint was W12 American College of Rheumatology 20% improvement; safety was assessed by adverse event (AE) reporting. For the LTE (NCT03025308), eligible filgotinib patients continued FIL200/FIL100; ADA patients were rerandomised (blinded) to FIL200 or FIL100; all continued MTX., Results: In all, 114/147 Japanese patients completed the PS, 115 enrolled in LTE, and 103 remained on study in June 2020. In the PS, AEs were consistent with the overall population, and W24 efficacy was maintained or improved through W52, comparable with the overall population. LTE AE incidences were similar between doses; filgotinib efficacy was consistent from baseline to W48 and similar between PS ADA and filgotinib patients., Conclusions: Among MTX-IR Japanese patients, filgotinib maintained efficacy over 1 year; LTE safety was consistent with the PS., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Introduction: This exploratory analysis of FINCH 1 (NCT02889796) examined filgotinib (FIL) efficacy and safety in a subgroup of patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX; MTX-IR) who had four poor prognostic factors (PPFs)., Methods: Patients with MTX-IR received placebo up to week (W)24 or FIL200 mg, FIL100 mg, or adalimumab up to W52; all received MTX. Efficacy and safety data were stratified by four PPFs versus fewer than four PPFs: seropositivity, high-sensitivity C-reactive protein (CRP) ≥ 6 mg/L, Disease Activity Score in 28 joints with CRP > 5.1, and erosions on X-rays., Results: At baseline, 687/1755 patients had four PPFs. At W12, whether with four PPFs or fewer than four PPFs, response rates on all American College of Rheumatology (ACR) measures were significantly greater with FIL200 and FIL100 versus placebo. At W52, FIL200 ACR20/50/70 response rates remained at least numerically higher versus adalimumab in both subgroups. At W52, FIL200 reduced modified total Sharp score (mTSS) change versus adalimumab in patients with four or fewer than four PPFs., Conclusions: In high-risk (four PPFs) patients with MTX-IR RA, FIL200 and FIL100 showed similar reductions in disease activity versus placebo at W12 as in patients with fewer than four PPFs. mTSS in patients receiving FIL200 changed little from W24 to W52, while that in patients receiving FIL100 progressed comparably to patients who received adalimumab. Tolerability was comparable across treatment arms and subgroups., (© 2022. The Author(s).)

Objectives: Evaluate the efficacy and safety of the Janus kinase-1 inhibitor filgotinib in Japanese patients with rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX)., Methods: Data from 147 Japanese patients in FINCH 1, a 52-week global Phase 3 study, were analysed up to 24 weeks. Patients received once-daily filgotinib 200 or 100 mg, biweekly adalimumab, or placebo, all with stable background MTX., Results: In the Japanese population, American College of Rheumatology 20% response rates at Week 12 (primary endpoint) were 77.5%, 65.9%, 53.6%, and 36.8% for filgotinib 200 mg, filgotinib 100 mg, adalimumab, and placebo. Proportions of patients achieving Disease Activity Score with 28 joints <2.6 at Week 24: filgotinib 200 mg, 65.0%; filgotinib 100 mg, 51.2%; adalimumab, 42.9%; and placebo, 5.3%. Incidence rates of serious infections: filgotinib 200 mg, 2.5%; filgotinib 100 mg, 0%; adalimumab, 10.7%; and placebo, 5.3%. Treatment-emergent laboratory abnormalities Grade ≥3 occurred in five (12.5%) filgotinib 200 mg, three (7.3%) filgotinib 100 mg, one (3.6%) adalimumab, and no placebo patients. No deaths were reported among Japanese patients., Conclusions: Filgotinib once daily combined with MTX was effective and generally safe and well tolerated up to Week 24 in Japanese patients with RA and inadequate response to MTX., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Objectives: To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing  Very Early Rheumatoid arthritis Treatment study (NCT01142726)., Methods: Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare. After ≥3 months' withdrawal, patients with protocol-defined RA flare received open-label abatacept plus methotrexate for 6 months (re-treatment)., Results: Proportion of patients in DAS28-CRP-defined remission remained numerically higher in original abatacept plus methotrexate and abatacept arms versus methotrexate arm up to day 253 of withdrawal. At the end of the withdrawal period, few patients remained in remission across all arms: 9/73 (12.3%), 7/50 (14.0%) and 6/53 (11.3%), respectively. For patients entering re-treatment, after 6 months' re-treatment, 95/124 (76.6%) and 78/124 (62.9%) patients achieved DAS28-CRP <3.2 and <2.6, respectively; mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index scores from re-treatment baseline were -2.87 and 0.76, respectively. Re-treatment was well tolerated; exposure-adjusted infection rates per 100 patient-years were lower with abatacept plus methotrexate during withdrawal (7.2) and re-treatment (17.2) versus initial treatment periods of months 0-6 (116.6) and 6-12 (64.6)., Conclusions: Most patients flared within 6 months of therapy withdrawal and few sustained major responses for 1 year. Re-treatment with abatacept plus methotrexate was effective and well tolerated in this controlled setting., Competing Interests: Competing interests: PE: grant/research support: AbbVie, Merck, Pfizer, Roche; consultant: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis, Samsung Bioepis. GRB: grant/research support: clinical trials for Bristol-Myers Squibb, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly; consultant: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, MedImmune, Roche, UCB; speakers bureau: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Roche, UCB. VPB: grant/research support: Amgen, Pfizer, Bristol-Myers Squibb, Janssen, UCB, Sanofi, Roche/Genentech; consultant: Amgen, AbbVie, Pfizer, Bristol-Myers Squibb, UCB, Roche, Regeneron. BGC: grant/research support: Pfizer, Roche-Chugai, UCB; honoraria/speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, Janssen, Lilly, Novartis, Sanofi. DEF: grant/research support: Amgen, Bristol-Myers Squibb, Pfizer, Roche/Genentech; consultant: AbbVie, Amgen, Bristol-Myers Squibb, Corbus, Cytori, Novartis, Pfizer, Roche/Genentech; speakers bureau: AbbVie, Bristol-Myers Squibb. MAM: shareholder and employee: Bristol-Myers Squibb. TWJH: grant/research support: EU and Dutch Arthritis Foundation; consultant: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, UCB, Eli Lilly; speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi, Schering-Plough.

Clinical outcomes in patients with early rheumatoid arthritis (RA) were assessed by baseline symptom duration in the Assessing Very Early Rheumatoid arthritis Treatment trial (ClinicalTrials.gov; NCT01142726). Patients with early, active RA were randomized to subcutaneous (SC) abatacept 125 mg/week plus methotrexate (MTX), SC abatacept alone, or MTX monotherapy for 12 months. All RA treatments were withdrawn after 12 months in patients with Disease Activity Score in 28 joints (C-reactive protein; DAS28-CRP) < 3.2. In this post hoc analysis, the proportion of patients achieving protocol-defined remission (DAS28-CRP < 2.6) or improvement in physical function at 12 and at both 12 and 18 months was assessed according to symptom duration (≤ 3 months, > 3 to ≤ 6 months, or > 6 months) and treatment group. No clinically significant differences were seen in baseline demographics or characteristics across symptom duration groups. Irrespective of baseline symptom duration, a numerically higher proportion of abatacept plus MTX-treated patients achieved DAS-defined remission at month 12 and sustained remission at month 18 compared with MTX monotherapy. A numerically higher proportion of abatacept plus MTX-treated patients with symptom duration ≤ 3 months maintained DAS-defined remission after complete treatment withdrawal from 12 to 18 months compared with longer symptom duration groups. This subgroup also had the fastest onset of clinical response (DAS28-CRP < 2.6) after initiation of treatment. Health Assessment Questionnaire-Disability Index response was similar regardless of baseline symptom duration. Overall, symptom duration of ≤ 3 months was associated with a faster onset of clinical response and higher rates of drug-free remission following treatment with abatacept plus MTX.

Objectives: To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity., Methods: Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population., Results: 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (-2.35 vs -0.68, -2.58 vs -0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (-1.34 vs -0.49 -2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX., Conclusions: Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity., Trial Registration Number: NCT01142726; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To evaluate clinical remission with subcutaneous abatacept plus methotrexate (MTX) and abatacept monotherapy at 12 months in patients with early rheumatoid arthritis (RA), and maintenance of remission following the rapid withdrawal of all RA treatment., Methods: In the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial, patients with early active RA were randomised to double-blind, weekly, subcutaneous abatacept 125 mg plus MTX, abatacept 125 mg monotherapy, or MTX for 12 months. Patients with low disease activity (Disease Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12-month period of withdrawal of all RA therapy. The coprimary endpoints were the proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and 18, for abatacept plus MTX versus MTX., Results: Patients had <2 years of RA symptoms, DAS28 (CRP) ≥3.2, anticitrullinated peptide-2 antibody positivity and 95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28 (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12 months, and following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18 months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month 12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile comparable with MTX alone., Conclusions: Abatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA, with a good safety profile. The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacept's mechanism on autoimmune processes., Trial Registration Number: NCT01142726., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)