A small, open-label study seeds the idea that IL-2 in low doses might be another avenue for treating ulcerative colitis. Low doses may bolster anti-inflammatory T regulatory cells (Tregs) that are believed to lack sufficient expansion in the disease.
Ulcerative colitis is a chronic, inflammatory, autoimmune condition with no current cure. Disease pathology is believed to stem from several factors, including the overproduction of inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukins (IL)-12 and -23. Several treatments exist (and more are in the making) that target these cytokines. Yet, many individuals with ulcerative colitis do not respond to treatment, and less than half achieve sustained remission.
Research is ongoing, exploring novel pathways for treatment. One study, recently published in the journal Gastroenterology, investigated the safety and potential use of IL-2 in treating ulcerative colitis. Proleukin (aldesleukin), marketed by British company Clinigen Group, is a human recombinant IL-2 product FDA-approved to treat metastatic renal cancer and melanoma in adults. At high doses, IL-2 activates inflammatory cell lines and cytokines that attack tumor cells. At low doses, it bolsters anti-inflammatory T regulatory cells (Tregs) that are believed to lack sufficient expansion in ulcerative colitis.
Jessica R. Allegretti, M.D., M.P.H., medical director of the Crohn's and Colitis Center at Bringham and Women’s Hospital in Boston, and her colleagues enrolled 26 adults with moderate to severe ulcerative colitis who had not responded to at least one other ulcerative colitis therapy in an eight-week, open-label, phase 1b/2a induction trial. The primary endpoints were the safety and tolerability of low-dose IL-2 (as Proleukin) and the determination of a maximum tolerated dose. Secondary endpoints included the evaluation of efficacy, as measured by clinical response and clinical remission based on change in Mayo scores.
Participants received Proleukin subcutaneous injections in a dose-escalation design, and Mayo scores were assessed at eight weeks. Clinical response was defined as a reduction in total Mayo score of 3 points or more or at least 30% at week eight. A total Mayo score of 2 or less, with no individual subscore of more than 1, was considered clinical remission.
After eight weeks of treatment, the more common adverse effects were mild and included injection site reactions, fever, and malaise. No serious adverse effects or deaths occurred. A total of 53% of participants had a clinical response, and 21% achieved clinical remission. Of the three doses tested, the most effective and tolerated was 1 x 106 IU/m2/day. This dosage achieved a clinical response in 69% of patients and remission in 31%.
Treg circulation expanded in all participants who had a clinical response and in 92% of those who achieved remission.
Allegretti and her colleagues conclude that low-dose IL-2 is well-tolerated and safe to use in patients with ulcerative colitis. They cite trial limitations as having a small sample size, lacking a placebo cohort, and having unblinded reading of study images. The researchers recommend larger clinical trials evaluating the safety and efficacy of low-dose IL-2 in the treatment of ulcerative colitis.