Intermittent And Short Term Empirical Ruxolitinib Regimen For Steroid

Leo Migdal

-Dec 5, 2025, 4:39 PM

intermittent and short term empirical ruxolitinib regimen for steroid

An official website of the United States government The .gov means it's official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Bone Marrow Transplantation volume 60, pages 69–78 (2025)Cite this article REACH2 and REACH3 were randomized, multicenter, open-label phase 3 studies comparing the selective Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib versus investigators’ choice of best available therapy (BAT) in steroid-refractory (SR) acute (REACH2) or chronic (REACH3)...

Moderate-severe aGVHD/cGVHD can progress rapidly; thus, key clinical considerations driving management of patients with SR-aGVHD/SR-cGVHD are prompt treatment initiation and concomitant cytopenias. These post hoc analyses of REACH2/REACH3 describe the impact of timing of treatment initiation after SR-aGVHD/SR-cGVHD diagnosis and development of concomitant cytopenias on treatment outcomes. Ruxolitinib initiation within 3 days from SR-aGVHD diagnosis yielded an extended duration of response and higher Day 28 complete response rates compared with initiation ≥7 days after SR-aGVHD diagnosis (median 178 vs 167 days... For patients with SR-cGVHD, Week 24 overall response was not impacted by time to treatment (54.5% vs 42.6% for <14 vs >28 days). Clinically relevant cytopenias were manageable, allowing for maintenance of dose intensity (median 20 mg/d), and did not impact the favorable efficacy outcomes from ruxolitinib treatment. This analysis highlights the practical importance of considering earlier ruxolitinib initiation after SR diagnosis in GVHD and the benefits of ruxolitinib treatment compared with BAT even for patients with cytopenias.

Graft-versus-host disease (GVHD) is a leading cause of morbidity and mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) [1,2,3]. Despite prophylactic immunosuppressive therapies, GVHD develops in ≈50% of allogeneic HSCT recipients. Acute GVHD (aGVHD) mainly affects skin, gastrointestinal (GI) tract, and liver, whereas chronic GVHD (cGVHD) commonly presents in the mouth, genitalia, liver, lungs, skin, GI tract, joints, and muscles [4, 5]. Corticosteroids are the current standard of care for initial GVHD therapy [4, 6,7,8,9]. Approximately 30–60% of patients with GVHD become refractory to treatment with corticosteroids [1, 10, 11]. Among patients with steroid-refractory (SR)-aGVHD, the 6-month survival rate is approximately 50% [8], whereas overall survival for patients with SR-cGVHD is approximately 72% at 3 years [12, 13].

Systemic corticosteroids have known severe treatment-related toxicities that limit long-term use [14]. For GVHD after failure of at least one line of systemic therapy, 3 therapies have been approved by the US Food and Drug Administration (FDA) since 2017: ibrutinib and belumosudil are approved for treatment... Per the prescribing information, the GVHD indications for ruxolitinib are SR-aGVHD in adult and pediatric patients ≥12 years and cGVHD after failure of 1–2 lines of systemic therapy in adult and pediatric patients ≥12... Correspondence: Donna Przepiorka, M.D., Ph.D., Office of Hematology and Oncology Products, CDER, U.S. Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, Maryland 20993, USA. Telephone: 301‐796‐5358; e‐mail: donna.przepiorka@fda.hhs.gov

Received 2019 Aug 14; Accepted 2019 Sep 20; Issue date 2020 Feb. On May 24, 2019, the Food and Drug Administration approved ruxolitinib for steroid‐refractory acute graft‐versus‐host disease (SR‐aGVHD) in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424‐271 (REACH‐1; NCT02953678), an open‐label, single‐arm, multicenter trial that included 49 patients with grades 2–4 SR‐aGVHD occurring after allogeneic hematopoietic stem cell transplantation. Ruxolitinib was administered at 5 mg twice daily, with dose increases to 10 mg twice daily permitted after 3 days in the absence of toxicity. The Day‐28 overall response rate was 57.1% (95% confidence interval [CI]: 42.2–71.2). The median duration of response was 0.5 months (95% CI: 0.3–2.7), and the median time from Day‐28 response to either death or need for new therapy for acute GVHD was 5.7 months (95% CI:...

Common adverse reactions included anemia, thrombocytopenia, neutropenia, infections, edema, bleeding, and elevated transaminases. Ruxolitinib is the first drug approved for treatment of SR‐aGVHD. Ruxolitinib is the first Food and Drug Administration–approved treatment for steroid‐refractory acute graft‐versus‐host disease in adult and pediatric patients 12 years and older. Its approval provides a treatment option for the 60% of those patients who do not respond to steroid therapy. Keywords: Ruxolitinib, Graft‐versus‐host disease, Hematopoietic stem cell transplantation Received 2020 Jan 6; Accepted 2020 Feb 8; Issue date 2020 May 14.

Publisher's Note: There is a Blood Commentary on this article in this issue. The Janus kinase (JAK)1/2 inhibitor ruxolitinib induced responses in more than half of patients with steroid-refractory aGVHD by day 28. Ruxolitinib was well tolerated, and the safety profile was consistent with expectations for ruxolitinib and this patient population. Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily... The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months.

As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days.

Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population. Introduction: Myelofibrosis (MF) is characterized by ineffective and hepatosplenic extramedullary hematopoiesis due to fibrotic changes in the bone marrow and systemic manifestations due to aberrant cytokine release.

Ruxolitinib (RUX) is the first JAK1/JAK2 inhibitor that is clinically approved to treat splenomegaly by ameliorating inflammatory cytokines and myeloproliferation in MF. Areas covered: Patients with less advanced MF may also achieve better outcome and successful treatment with RUX. However, approximately 40% of the patients failed to achieve a stable response or have shown to be intolerant to RUX, and most of them discontinued RUX. In patients who need to discontinue or reduce the dose of RUX for any reason, RUX is known to induce a paradoxical accumulation of JAK activation loop phosphorylation that is causing RUX discontinuation syndrome... To review the topic of MF and RUX, we searched relevant literatures using PubMed. Expert opinion: RUX treatment in lower IPSS risk patients who present with splenomegaly and disease-associated symptoms can be helpful.

A careful discontinuation strategy with steroids may reduce the probability of RDS, and the recognition of RDS with early re-introduction of RUX is important in the treatment of severe cases of RDS. Keywords: Myelofibrosis; adverse events; early treatment; ruxolitinib; ruxolitinib discontinuation syndrome.

Intermittent And Short Term Empirical Ruxolitinib Regimen For Steroid

People Also Search

An Official Website Of The United States Government The .gov

NCBI Bookshelf. A Service Of The National Library Of Medicine,

Moderate-severe AGVHD/cGVHD Can Progress Rapidly; Thus, Key Clinical Considerations Driving

Graft-versus-host Disease (GVHD) Is A Leading Cause Of Morbidity And

Systemic Corticosteroids Have Known Severe Treatment-related Toxicities That Limit Long-term