Filgotinib 100mg tablets

A Bayesian network meta-analysis was conducted to examine the radiographic and clinical efficacy of the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, upadacitinib, and filgotinib and the biologic disease-modifying antirheumatic drug (bDMARD) adalimumab (all given with methotrexate [MTX]) in patients with rheumatoid arthritis (RA) and an inadequate response to MTX (MTX-IR). The PubMed database was systematically searched to identify relevant randomized controlled trials. Efficacy outcomes included the modified total Sharp score (mTSS), erosion, joint space narrowing, 70% improvement in American College of Rheumatology criteria (ACR70), Boolean remission, Clinical Disease Activity Index (CDAI) score ≤ 2.8, and Simplified Disease Activity Index (SDAI) score ≤ 3.3. Five studies were identified using the inclusion criteria, and two additional publications presented further results from one of the five studies, with the total meta-analysis population comprising 6933 patients. Among all JAK inhibitors analyzed and the bDMARD adalimumab, filgotinib 200 mg had the highest probability of being the treatment with the greatest improvement in mTSS versus placebo at 48/52 weeks, followed by filgotinib 100 mg, adalimumab 40 mg, baricitinib 4 mg, and upadacitinib 15 mg. Filgotinib 200 mg also had the highest probability of being the treatment with the greatest improvement in erosion and joint space narrowing at 48/52 weeks versus the same comparators. At 12 weeks, filgotinib 200 mg had the highest probability versus other JAK inhibitors and adalimumab of achieving clinical remission (CDAI ≤ 2.8 and SDAI ≤ 3.3). Varying treatments had the highest probability of achieving other efficacy outcomes of interest at 12, 24/26, and 48/52 weeks. In the absence of head-to-head comparisons, this analysis provides valuable evidence for the role of filgotinib in the treatment of patients with MTX-IR RA.

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OBJECTIVE: Janus kinase inhibitors (JAKinibs) are efficacious in rheumatoid arthritis (RA) with variable reported rates of adverse events, potentially related to differential JAK family member selectivity. Filgotinib was compared with baricitinib, tofacitinib and upadacitinib to elucidate the pharmacological basis underlying its clinical efficacy and safety. METHODS: In vitro JAKinib inhibition of signal transducer and activator of transcription phosphorylation (pSTAT) was measured by flow cytometry in peripheral blood mononuclear cells and whole blood from healthy donors and patients with RA following cytokine stimulation of distinct JAK/STAT pathways. The average daily pSTAT and time above 50% inhibition were calculated at clinical plasma drug exposures in immune cells. The translation of these measures was evaluated in ex vivo-stimulated assays in phase 1 healthy volunteers. RESULTS: JAKinib potencies depended on cytokine stimulus, pSTAT readout and cell type. JAK1-dependent pathways (interferon (IFN)α/pSTAT5, interleukin (IL)-6/pSTAT1) were among the most potently inhibited by all JAKinibs in healthy and RA blood, with filgotinib exhibiting the greatest selectivity for JAK1 pathways. Filgotinib (200 mg once daily) had calculated average daily target inhibition for IFNα/pSTAT5 and IL-6/pSTAT1 that was equivalent to tofacitinib (5 mg two times per day), upadacitinib (15 mg once daily) and baricitinib (4 mg once daily), with the least average daily inhibition for the JAK2-dependent and JAK3-dependent pathways including IL-2, IL-15, IL-4 (JAK1/JAK3), IFNγ (JAK1/JAK2), granulocyte colony stimulating factor, IL-12, IL-23 (JAK2/tyrosine kinase 2) and granulocyte-macrophage colony-stimulating factor (JAK2/JAK2). Ex vivo pharmacodynamic data from phase 1 healthy volunteers clinically confirmed JAK1 selectivity of filgotinib. CONCLUSION: Filgotinib inhibited JAK1-mediated signalling similarly to other JAKinibs, but with less inhibition of JAK2-dependent and JAK3-dependent pathways, providing a mechanistic rationale for its apparently differentiated efficacy:safety profile.

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Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

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1 40 countries. 4Filgotinib has a rapid mechanism of action, oral administration drug, and innovative drug for patients with corticosteroid-resistant and corticosteroid-dependent UC.However, there is no algorithm or randomized controlled trials that positions this drug over currently approved drugs for moderate to severe UC patients. 5Therefore, the predictive factors associated the good clinical outcomes could be useful in decision-making and personalize healthcare clinical practice. 6orticosteroid-free remission is an important treatment target in UC patients, and the corticosteroid-sparing effects of filgotinib was investigated in the previous post hoc analyses of the SELECTION study. 7Corticosteroid-free remission rate in patients receiving filgotinib was 30.4%, 29.3%, 27.2%, and 21.7% at 1, 3, 6, and 8 months, respectively.During the maintenance study, the median daily prednisone-equivalent dose decreased from 17.5 mg/day to 10.0 mg/day with filgotinib treatment.In the current issue, Kobayashi et al. 8 investigated the independent prognostic factors of achieving corticosteroid-free remission in patients of UC treated with filgotinib by post hoc analysis of the phase 2b/3 SELECTION study.This article suggested that corticosteroid-free remission was higher in patients who were biologic-nave, current smokers, had low endoscopic inflammatory burden and who were female.

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Introduction: Acute severe ulcerative colitis (ASUC) is a serious complication affecting 9%-15% of patients with UC within 3 months of diagnosis and up to 28% of patients during the course of the disease. Despite the use of infliximab and calcineurin inhibitors, the rate of colectomy remains high both during the hospitalization and in the 5 years after an acute episode. We present a case of ASUC that was unresponsive to conventional therapies but was successfully treated with filgotinib. Case Presentation: A 21-year-old male with a recent diagnosis of UC presented to our hospital with a severe flare. He received rescue therapy of high-dose intravenous steroids and 10 mg/kg infliximab. We observed little clinical and biochemical benefits. The patient declined the surgical option. Therefore, we decided to start a second rescue therapy with a new and rapid-acting Janus kinase inhibitor, filgotinib, due to its characteristics and pharmacokinetic profile of rapid absorption and metabolism. The patient showed an immediate clinical and biochemical response at 48 h, an endoscopic response at week 3, and an endoscopic remission at week 10. No recurrence was observed after 12 months of follow-up. The patient is in clinical remission with a good quality of life. Conclusion: Filgotinib may be an effective second-line therapy in an emergency setting such as ASUC in patients unresponsive to conventional therapy.

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