OP0126 IS IMMUNE CHECKPOINT INHIBITORS THERAPIES SAFE AND EFFECTIVE FOR PATIENTS WITH CANCER AND PREEXISTING AUTOIMMUNE DISEASE?
Authors: W. Xie, H. Huang, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2020)

Background: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs). Most patients with preexisting autoimmune disease (PAD) have been universally excluded from clinical trials and ICIs are not recommended for patients with cancer and PAD due to the unknown safety. In this study, we aim to evaluate the safety and efficacy of ICIs in patients with PAD and cancer. Objectives: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through September 2019 for observational studies reporting safety and efficacy data among ICIs-treated patients with cancer and PAD. A random effects meta-analysis was performed to calculate pooled incidence rates of PAD flare, irAEs and response. Methods: Systematical search of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed for observational studies that reported cancer incidence in patients with RA treated with biologics or tofacitinib with active comparator of conventional DMARDs (csDMARDs) or TNFi. The pooled relative risk (RR) and 95% confidence interval (CI) were calculated with fix-effects or random-effects model. Results: A total of 619 ICI-treated patients with PAD in 14 publications were finally identified. In the random effects meta-analysis, pooled incidence of PAD flares, de novo irAEs or both of any grade was 60% (95% CI 52%-68%). Viewed separately, there were 219 and 206 patients experiencing PAD exacerbation and de novo irAEs of any grade, yielding a pooled incidence of 35% (95% CI 29%-41%) and 33% (95% CI 24%-42%) respectively. Of these, most of flare and de novo irAEs were graded as mild (grade 1-2) (pooled proportion: 82%, 95%CI 72%-91%; 65%, 95%CI 54%-76%, respectively). Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR=1.25-1.88). With respect to efficacy, 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95% CI 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR: 1.08, 95% CI 0.72-1.62), but a trend towards lower response rates was observed in patients with baseline immunosuppressants (RR: 0.58, 95% CI 0.26-1.33). Conclusion: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. Rheumatoid arthritis is associated with a trend toward more flares. ICI treatment are effective and not absolute contraindication in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis. References: [1]Khan SA, Pruitt SL, Xuan L et al. Prevalence of autoimmune disease among patients with lung cancer: Implications for immunotherapy treatment options. JAMA Oncol 2016;2:1507-1508. Figure 1. Pooled effect estimates in ICI-treated patient with PAD (A) PAD flare, de novo irAEs or both; (B) PAD flare; (C) de novo irAEs. ICI: Immune checkpoint inhibitors; PAD: Preexisting autoimmune disease; irAEs: Immune-related adverse events. Disclosure of Interests: None declared