Jakafi (ruxolitinib)

P1/2, N=48, Active, not recruiting, Universita' Degli Studi Di Perugia | Recruiting --> Active, not recruiting

For management, we evaluate conventional therapies (corticosteroids, etoposide) and emerging immunomodulatory agents (anakinra, ruxolitinib, emapalumab), emphasizing the 2023 treatment regimen by the American Society of Transplantation and Cellular Therapy (ASTCT). By integrating risk stratification, early diagnostic criteria, and tailored therapeutic approaches, this review aims to improve clinical outcomes for IEC-HS patients.

Treatment with hydroxycarbamide and ruxolitinib resulted in decreased platelet counts and improved vasculitis, with no subsequent recurrence of cardiovascular events. This rare case shows that ruxolitinib can be effective in treating vasculitis complications in patients with JAK2 mutation-positive ET.

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.

P2, N=121, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2027 --> Jan 2026 | Trial primary completion date: Apr 2027 --> Jan 2026

P1, N=210, Active, not recruiting, iOnctura | Trial completion date: Mar 2025 --> Mar 2027

P2, N=61, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

P1/2, N=33, Active, not recruiting, Suzhou Junjing BioSciences Co., Ltd. | Recruiting --> Active, not recruiting | N=49 --> 33

P4, N=268, Not yet recruiting, SWOG Cancer Research Network

Adults with hydroxyurea-resistant/intolerant PV were randomized 1:1 to ruxolitinib or BAT; crossover to ruxolitinib was allowed after primary analysis. Patients receiving ruxolitinib experienced decreased JAK2V617F allele burden, durable hematocrit control, and better symptom improvements versus BAT, reinforcing ruxolitinib clinical benefit. RESPONSE: https://clinicaltrials.gov/study/NCT01243944; RESPONSE-2: https://clinicaltrials.gov/study/NCT02038036.

Despite resistance to multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs), including adalimumab and tocilizumab, treatment with the Janus kinase 1/2 inhibitor ruxolitinib achieved clinical remission sustained for over two years without significant adverse events or lymphoma relapse. Ruxolitinib may represent a viable therapeutic option for refractory secondary JIA post-allo-HSCT, particularly when conventional bDMARDs fail.

The FMF-02 trial is the first randomized phase IIb study directly comparing the novel inhibitor FM against RUX. Its findings are expected to generate pivotal evidence regarding whether FM offers superior or differentiated clinical benefits, thereby informing its potential as a frontline therapy for intermediate- to high-risk MF and guiding the design of future phase III studies.