Latest news with #Tofacitinib
Medscape
11-07-2025
- Health
- Medscape
Good News for Tofacitinib in Recent Study of Acute Severe UC
A head-to-head comparison of the JAK inhibitor drug tofacitinib and chimeric monoclonal antibody infliximab in the treatment of acute severe ulcerative colitis (ASUC) shows that, contrary to concerns, tofacitinib is not associated with worse postoperative complications and in fact may reduce the risk of the need for colectomy. 'Tofacitinib has shown efficacy in managing ASUC, but concerns about postoperative complications have limited its adoption,' reported the authors in research published in Clinical Gastroenterology and Hepatology. 'This study shows that tofacitinib is safe and doesn't impair wound healing or lead to more infections if the patient needs an urgent colectomy, which is unfortunately common in this population,' senior author Jeffrey A. Berinstein, MD, of the Division of Gastroenterology and Hepatology, Michigan Medicine, Ann Arbor, Michigan, told Medscape Medical News. Recent treatment advances for UC have provided significant benefits in reducing the severity of symptoms; however, about a quarter of patients go on to experience flares, with fecal urgency, rectal bleeding, and severe abdominal pain of ASUC potentially requiring hospitalization. The standard of care for those patients is rapid induction with intravenous (IV) corticosteroids; however, up to 30% of patients don't respond to those interventions, and even with subsequent treatment of cyclosporine and infliximab helping to reduce the risk for an urgent colectomy, patients often don't respond, and ultimately, up to a third of patients with ASUC end up having to receive a colectomy. While JAK inhibitor therapies, including tofacitinib and upadacitinib, have recently emerged as potentially important treatment options in such cases, showing reductions in the risk for colectomy, concerns about the drugs' downstream biologic effects have given many clinicians reservations about their use. 'Anecdotally, gastroenterologists and surgeons have expressed concern about JAK inhibitors leading to poor wound healing, as well as increasing both intraoperative and postoperative complications, despite limited data to support these claims,' the authors wrote. To better understand those possible risks, first author Charlotte Larson, MD, of the Department of Internal Medicine, Michigan Medicine, and colleagues conducted a multicenter, retrospective, case-control study of 109 patients hospitalized with ASUC at two centers in the US and 14 in France. Of the patients, 41 were treated with tofacitinib and 68 with infliximab prior to colectomy. Among patients treated with tofacitinib, five (12.2%) received infliximab and four (9.8%) received cyclosporine rescue immediately prior to receiving tofacitinib during the index admission. In the infliximab group, one (1.5%) received rescue cyclosporine. In a univariate analysis, the tofacitinib-treated patients showed significantly lower overall rates of postoperative complications than infliximab-treated patients (31.7% vs 64.7%; odds ratio [OR], 0.33; P = .006). The tofacitinib-treated group also had lower rates of serious postoperative complications (12% vs 28.9; OR, 0.20; P = .016). After adjusting for multivariate factors including age, inflammatory burden, nutrition status, 90-day cumulative corticosteroid exposure and open surgery, there was a trend favoring tofacitinib but no statistically significant difference between the two treatments in terms of serious postoperative complications ( P = .061). However, a significantly lower rate of overall postoperative complications with tofacitinib was observed after the adjustment (odds ratio, 0.38; P = .023). Importantly, a subanalysis showed that the 63.4% of tofacitinib-treated patients receiving the standard FDA-approved induction dose of 10 mg twice daily did indeed have significantly lower rates than infliximab-treated patients in terms of serious postoperative complications (OR, .10; P = .031), as well as overall postoperative complications (OR, 0.23; P = .003), whereas neither of the outcomes were significantly improved among the 36.6% of patients who received the higher-intensity thrice-daily tofacitinib dose ( P = .3 and P = .4, respectively). Further complicating the matter, in a previous case-control study that the research team conducted, it was the off-label, 10 mg thrice-daily dose of tofacitinib that performed favorably and was associated with a significantly lower risk for colectomy than the twice-daily dose (hazard ratio 0.28; P = .018); the twice-daily dose was not protective. Berinstein added that a hypothesis for the benefits overall, with either dose, is that tofacitinib's anti-inflammatory properties are key. 'We believe that lowering inflammation as much as possible, with the colon less inflamed, could be providing the benefit in lowering complications rate in surgery,' he explained. Regarding the dosing, 'it's a careful trade-off,' Berinstein added. 'Obviously, we want to avoid the need for a colectomy in the first place, as it is a life-changing surgery, but we don't want to increase the risk of infections.' In other findings, the tofacitinib group had no increased risk for postoperative venous thrombotic embolisms (VTEs), which is important as tofacitinib exposure has previously been associated with an increased risk for VTEs independent of other prothrombotic factors common to patients with ASUC, including decreased ambulation, active inflammation, corticosteroid use, and major colorectal surgery. 'This observed absence of an increased VTE risk may alleviate some of the hypothetical postoperative safety concern attributed to JAK inhibitor therapy in this high-risk population,' the authors wrote. Overall, the results underscore that 'providers should feel comfortable using this medication if they need it and if they think it's most likely to help their patients avoid colectomy,' Berinstein said. 'They should not give pause over concerns of postoperative complications because we didn't show that,' he said. Commenting on the study, Joseph D. Feuerstein, MD, of the Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, noted that, in general, in patients with ASUC who fail on IV steroids, 'the main treatments are infliximab, cyclosporine, or a JAK inhibitor like tofacitinib or upadacitinib, [and] knowing that if someone needs surgery, the complication rates are similar and that pre-operative use is okay is reassuring.' Regarding the protective effect observed with some circumstances, 'I don't put too much weight into that,' he noted. '[One] could speculate that it is somehow related to faster half-life of the drug, and it might not sit around as long,' he said. Feuerstein added that 'the study design being retrospective is a limitation, but this is the best data we have to date.'
Time of India
02-05-2025
- Health
- Time of India
New study finds tofacitinib effective and affordable for refractory atopic dermatitis
New Delhi: New Delhi: Tofacitinib , a Janus kinase (JAK) inhibitor drug, used either as a standalone treatment or alongside other drugs to address moderate to severe cases of rheumatoid arthritis and ankylosing spondylitis, demonstrates effectiveness in managing refractory atopic dermatitis (AD). Tired of too many ads? go ad free now This was revealed in a study published in the Indian Dermatology online journal. Atopic dermatitis (AD) presents as a long-term, recurring inflammatory disorder of the skin, and its characteristic itching significantly affects patients' daily living standards. The research was conducted at the department of dermatology, venereology and leprosy in Atal Bihari Vajpayee Institute of Medical Sciences and Research Institute and Dr Ram Manohar Lohia Hospital. The results established that people who previously showed no response to standard systemic treatments, including oral corticosteroids, cyclosporine and azathioprine, exhibited significant clinical improvement when administered tofacitinib exclusively. The progress was evaluated through decreased Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and Numerical Rating Scale (NRS) measurements at 4-week and 8-week intervals. The principal investigator of the study and dermatologist at RML Hospital, professor Kabir Sardana, explained that their main goal was to evaluate how well tofacitinib worked and its side effects in patients with difficult-to-treat moderate-to-severe AD. Additionally, they aimed to analyse the treatment costs between tofacitinib and dupilumab (approved by the Central Drugs Standard Control Organisation, India) for moderate and severe AD cases. Tired of too many ads? go ad free now The research indicated an average disease duration of three years. Patients displayed moderate to severe pruritus, excoriations, erythema, oozing and crusting. All participants had previously experienced treatment failure or intolerance to systemic therapy; 50% of patients also had other atopic conditions and bronchial asthma. The researchers continued treatment with topical corticosteroids, moisturiser and topical calcineurin inhibitors alongside tofacitinib. Improvements were observed in pruritus, sleep quality, affected body surface area, erythema, excoriation, papulation/edema and lichenification, with notable severity score reductions at four weeks and eight weeks of therapy. Dr Sardana said that EASI 90 was attained by 66% of patients within 8 weeks, with one patient experiencing treatment failure. Patients achieved complete or near-complete disease resolution in an average of 6.1 weeks (ranging from 3-8 weeks). Disease recurrence was observed in 36.3% of patients. Adverse reactions occurred in 41.6% of patients, including herpes zoster, dyslipidemia, anaemia, impetigo, and thrombocytosis. The financial comparison revealed that dupilumab (a monoclonal antibody used to treat various allergic conditions, including atopic dermatitis, asthma, and nasal polyps) therapy costs 122 times more than tofacitinib treatment over an 8-week period.
