Despite flare prevalence with checkpoint inhibitors, patients with RA rarely discontinue
ATLANTA — Although disease flares were common among patients with rheumatoid arthritis who received immune checkpoint inhibitors to treat concomitant malignancies, the symptoms were mostly manageable and few patients discontinued the treatment, according to findings presented at the 2019 ACR/ARP Annual Meeting.
“In our retrospective cohort analysis, [we looked at patients] that have a preexisting autoimmune condition and were also treated with immune checkpoint inhibitor therapy for their malignancy,” Sabina Sandigursky, MD, MS, instructor in the division of rheumatology at New York University Langone Medical Center, said during a press conference.
“The problem is that, in malignancy, patients with autoimmunity are excluded from clinical trials, and we know that patients with autoimmune conditions, including rheumatoid arthritis, have a higher risk for malignancy,” she added. “We wanted to understand in the real world, what happens to patients that are actually treated without any data to support the possible outcomes.”
To determine the safety and efficacy of immune checkpoint inhibitors (ICI) among these patients, Sandigursky and colleagues conducted a retrospective chart review of patients with autoimmune disorders who developed malignancies (n = 84), focusing on anti-CTLA-4 and anti-PD-1 therapies. The researchers considered primary endpoints the incidence of immune-related adverse events (irAEs) and autoimmune diseases flares, with a secondary endpoint of overall survival.
Among the autoimmune cohort, the researchers identified 22 patients with RA, 86% of whom (n = 19) exhibited no evidence of active disease according to their physicians. Malignancies reported in this cohort included seven patients with melanoma (32%), seven with non-small cell lung cancer (32%), as well as other malignancies; ICI therapy for these patients included 59% receiving pembrolizumab (Keytruda, Merck), 41% receiving nivolumab (Opdivo, Bristol-Myers Squibb), and 23% receiving ipilimumab (Yervoy, Bristol-Myers Squibb).
When ICI therapy was initiated among these patients, 73% were still receiving immunomodulatory therapy for RA, such as systemic corticosteroids (55%) and methotrexate (32%).
According to study results, the average overall survival for RA patients after initiating ICI therapy was 10.5 months. During the study, irAEs occurred in just 32% of patients with only 9% developing grade 3 or 4 irAEs. The most common adverse events were dermatitis (18%) and colitis (14%). Five patients (23%) temporarily discontinued ICIs due to irAEs, and 12 patients (55%) experienced RA flares — only one patient required permanent ICI discontinuation.
“We found that approximately 50% of patients had a flare of their preexisting rheumatoid arthritis, however, they were adequately treated with either steroids or non-steroid disease modifying agents,” Sandigursky said. “We also saw that these patients experienced some immune-related adverse events that were distinct from their preexisting rheumatoid arthritis symptoms; however, these were not indications for patients to discontinue their treatments necessarily. A few patients did discontinue, but most were able to continue on their immunotherapy.”
Additionally, the researchers reported that although a flare, irAEs, or both occurred in 73% of patients, these events occurred at a rate similar to populations without autoimmune diseases.
Sandigursky noted that “the punchline of this study suggests that patients with rheumatoid arthritis should not be excluded from standard of care malignancy treatment such as immune checkpoint inhibitor therapy.”– by Robert Stott
Sandigursky S. Abstract #1339. Risk of immunotherapy related toxicity in patients with rheumatoid arthritis. Presented at American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting, Nov. 8-13, 2019; Atlanta.
Disclosure: Sandigursky reports no relevant financial disclosures.