tofacitinib

The pan-JAK inhibitor tofacitinib (TOF) has emerged as an effective therapeutic option for inducing and maintaining clinical remission in moderate-to-severe UC. Comprehensive in vitro and in vivo assessments of mEXOs@TOF confirmed the enhanced anti-inflammatory treatment on UC, with no detectable adverse effects. Collectively, the mEXOs@TOF nanodelivery system represents a targeted therapeutic strategy for improving UC treatment.

P3, N=42, Recruiting, Assistance Publique - Hôpitaux de Paris | Suspended --> Recruiting

P2, N=180, Completed, CAGE Bio Inc. | Recruiting --> Completed

P2, N=3, Completed, CAGE Bio Inc. | Not yet recruiting --> Completed

The conventional sequencing of therapies in acute severe ulcerative colitis-i.e., intravenous steroids followed, in case of refractoriness, by antitumor necrosis factor (TNF) agents, ciclosporin A, or Janus kinase inhibitors such as tofacitinib or upadacitinib-may frequently be contraindicated in older patients or may carry an increased risk of severe adverse events beyond infections. In the absence of specific guidelines, the implementation of and strict adherence to a structured, time-bound decision tree is essential in order to avoid unnecessarily prolonged treatment with systemic steroids in frail patients, which may lead to deleterious outcomes, particularly in those requiring surgery. Recent reports on adjunctive measures, such as hyperbaric oxygen therapy or total enteral nutrition, may also be considered given their encouraging safety profile.

Over the past two decades, the field has progressed from the identification of early JAK2 inhibitors to the approval of several first-generation agents, including ruxolitinib, tofacitinib, baricitinib, and fedratinib, which validated the clinical feasibility of JAK blockade. Together, these multidisciplinary approaches have accelerated hit discovery, refined selectivity, and improved the pharmacokinetic and safety profiles of emerging JAK inhibitors. By consolidating progress across medicinal chemistry, structural biology, and computational design, this review outlines key opportunities and remaining challenges in developing next-generation JAK inhibitors with enhanced precision and therapeutic value for oncology, immunology, and chronic inflammatory diseases.

P3, N=118, Recruiting, Pfizer | Active, not recruiting --> Recruiting

The review was enriched by the inclusion of a new case: a 60-year-old woman who developed anti-MDA5-positive dermatomyositis two weeks after receiving her fourth dose of the BNT162b2 (Pfizer/BioNTech) vaccine. Treatment with oral prednisone, intravenous alprostadil, and the Janus kinase inhibitor tofacitinib resulted in marked clinical improvement. This case, together with the literature review, illustrates both typical and atypical presentations of vaccine-associated anti-MDA5 DM, highlights diagnostic challenges without lung involvement, and suggests JAK inhibition as a potential therapeutic option, contributing to a more comprehensive understanding of post-vaccination dermatomyositis.

P=N/A, N=186, Recruiting, The Fourth Affiliated Hospital of Zhejiang University School of Medicine | Not yet recruiting --> Recruiting

P=N/A, N=80, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Increased use of JAKi in the management of IMIDs is ongoing and will accelerate if the positive results noted in trials for lupus, inflammatory myopathies, and psoriatic arthritis result in regulatory approval. The article highlighted in this review provide an update on the progress being made in newer rheumatic disease indications as well as efforts to better understand the adverse event profile for patients on treatment.

P4, N=34, Completed, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh