Autoimmune inflammatory myopathy after treatment with ipilimumab.

While human immunity is generally thought to protect against infectious agents, there is also evidence for immune surveillance against neoplastic diseases. Some malignant cells are able to evade or down-regulate this immune response through a variety of chemical mediators, rendering the host response ineffective and leading to poor prognoses. Immune mechanisms seem particularly important in the pathogenesis of malignant melanoma, prompting research into potential immune mediated therapies. Ipilimumab is a novel humanized monoclonal antibody directed against cytotoxic T lymphocyte antigen 4 (CTLA-4), a T-cell surface molecule involved in down-regulation and suppression of the T cell response to stimuli1. Suppression of CTLA-4 may improve immune surveillance and have an antineoplastic effect, and early studies of ipilimumab in patients with various malignancies have been encouraging, demonstrating prolonged time to progression and tumor regression2,3. The most commonly reported adverse effects (AE) associated with anti-CTLA-4 treatment are autoimmune in nature, and include dermatitis in approximately 35%4, and enterocolitis in 10-15%5,6. These AE may occur soon after treatment with ipilimumab7. Rarely reported AEs include hepatitis, uveitis, and hypophysitis. The vast majority of immune-related adverse effects (IRAE) respond well to steroids, but preclude further treatment with antiCTLA-4 therapies. Interestingly, IRAE after ipilimumab treatment are associated with an improved prognosis, and outcome seems to correlate with the grade of AE. Attia and colleagues demonstrated tumor regression in 36% of patients with a grade III or IV IRAE, vs. 5% of those with no IRAE2. Beck et al8 reported similar findings in their series. To date, no neuromuscular IRAE have been associated with ipilimumab. We are now reporting the first case of autoimmune polymyositis in association with ipilimumab treatment, and discuss potential implications of CTLA-4 in neurologic disease and therapeutics.