Ruxolitinib takes spot as reference JAK inhibitor for myelofibrosis

Different Janus kinase (JAK) inhibitors exhibit differing degrees of efficacy and tolerability against myelofibrosis, a recent meta-analysis has found. In particular, ruxolitinib appears to be the best choice and is a good option as the reference JAK inhibitor.

Researchers conducted a systematic review and network meta-analysis on seven randomized controlled trials corresponding to 1,953 patients. Four JAK inhibitors were assessed: ruxolitinib, fedratinib, pacritinib, and momelotinib. The outcomes were efficacy for reducing total symptom score (TSS) and spleen volume. Studies were retrieved from the databases of PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, as well as from meetings of major haematological societies.

After removing studies due to heterogeneity, five remained eligible for the pooled analysis of efficacy, including 1,576 patients. Fedratinib, momelotinib, and ruxolitinib were able to induce significant improvements in the sustained virological rate (SVR) of at least 35 percent at 24 weeks relative to placebo.

In addition, ruxolitinib and momelotinib further led to a significantly higher rates of achieving the primary endpoint in comparison with pacritinib, while fedratinib failed to demonstrate the same. Fedratinib, momelotinib, and ruxolitinib were all statistically comparable as regards SVR.

The secondary efficacy endpoint was TSS reduction by at least 50 percent by 24 weeks, for which both ruxolitinib and fedratinib proved to be statistically superior to placebo.

“Altogether, our results support the place of ruxolitinib as the reference JAK inhibitor, closely followed by fedratinib, for reducing splenomegaly and improving disease-related symptoms,” the researchers said. Nevertheless, the choice of a JAK inhibitor could also depend on the line of treatment and subsequent risks of anaemia and thrombocytopaenia.

“In this regard, momelotinib could be confirmed as a valuable option in case of anaemia and fedratinib in case of thrombocytopenia. Pacritinib should be confirmed as a valuable option in a second-line setting after prior JAK inhibitor exposure,” they added.