The safety, biologic efficacy, and potential clinical efficacy of low-dose interleukin-2 (ld-IL2) has been observed among patients with a variety of autoimmune and inflammatory chronic diseases, according to the results of the interventional, prospective, open-label, phase 1-2a TRANSREG study (ClinicalTrials.gov identifier: NCT01988506) published in the Annals of the Rheumatic Diseases.
Individuals with a mild to moderate form of 1 of 11 autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, Behcet disease, Crohn disease, ulcerative colitis, granulomatosis with polyangiitis, Takayasu disease, autoimmune hepatitis, or sclerosing cholangitis) were evaluated. The investigators sought to assess the role played by ld-IL2 in expanding and activating regulatory T cells (Tregs), which have been shown to prevent autoimmunity and control inflammation among those with a variety of inflammatory and autoimmune conditions. In fact, among those with an autoimmune or inflammatory disorder, an insufficiency in Tregs has been demonstrated.
A total of 46 patients with a mild to moderate autoimmune disease were evaluated. All participants received ld-IL2 (1 million IU/d) for 5 days (the induction period), which was followed by injections every 2 weeks for 6 months (the maintenance period). The primary study end point was change in the relative concentration of peripheral blood Tregs on day 8 compared with baseline. Biologic secondary end points included area under the curve of the changes from baseline in relative concentration of Tregs during the maintenance period, and changes in inflammatory biomarkers from baseline to the conclusion of therapy. Clinical secondary end points included Clinical Global Impression and disease-specific and Five-level EuroQoL Five-dimensional scores. Furthermore, chronic fatigue and arthralgia were also assessed by physicians at baseline, 3 months, and 6 months.
Regardless of a participant’s type of autoimmune disease, the use of ld-IL2 was well tolerated. Thorough supervised and unsupervised immunomonitoring revealed specific Treg activation and expansion in all participants, with no effector T-cell activation. Moreover, an indication of potential clinical efficacy was observed.
The results of this study should license the initiation of randomized controlled efficacy trials in numerous indications to confirm these preliminary promising findings and ascertain the therapeutic potential of ld-IL2.
Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial [published online November 24, 2018]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2018-214229