Mark A. Schroeder, MD, an associate professor at the Washington University School of Medicine in St. Louis, discusses the importance of JAK inhibition in graft-versus-host disease (GVHD).

New therapies are emerging for patients with acute GVHD, such as JAK inhibitors, α-1 antitrypsin, and a novel agonist antibody called IL-22. JAK inhibition works by blocking cytokines, which are essential for stimulating GVHD response. JAK-STAT signaling is critical for immune cell development, says Schroeder. By blocking this signaling pathway with a JAK inhibitor, such as ruxolitinib (Jakafi) or itacitinib, you can block these essential signals, which are critical for T-cell proliferation.

A critical cytokine called interferon-gamma signals through JAK1/2. JAK1/2 inhibition prevents T cells from reaching the organs that are involved with GVHD, such as the gut, and other sites of GVHD, says Schroeder. Blocking interferon gamma or other cytokines decreases the inflammatory milieu of GVHD and effects the presentation of antigens in the stimulation of T cell response. Recently, other groups have shown that blocking interferon-gamma signaling, specifically in the gut, decreases damage to essential cells that regenerate the gut, concludes Schroeder.

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Mark A. Schroeder, MD, discusses the importance of JAK inhibition in graft-versus-host disease (GVHD).

Dr. Schroeder on the Importance of JAK Inhibition in GVHD

Mark A. Schroeder, MD, an associate professor at the Washington University School of Medicine in St. Louis, discusses therapies currently available and being investigated to treat patients with graft-versus-host disease (GVHD).

The only FDA-approved therapy for treating patients with GVHD is ruxolitinib (Jakafi), explains Schroeder. The administration of ruxlotinib depends on the institution and patient, including whether they can tolerate oral medicine. If not, there are other avenues of decreasing T-cell proliferation to help the damage induced by GVHD that could be given intravenously, says Schroeder.

There is currently no standard of care for steroid-refractory GVHD, but ruxolitinib seems to be the most common choice, according to Schroeder. The overall response rates on day 28 of a phase II trial (NCT02953678) were 100% for grade 2 GVHD, 40.7% for grade 3 GVHD, and 44.4% for grade 4 GVHD. Other novel therapies in development, as prophylaxis or treatment, that will be explored in larger randomized trials, concludes Schroeder.

Mark A. Schroeder, MD, discusses therapies currently available and being investigated to treat patients with graft-versus-host disease.

Mark A. Schroeder, MD

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