Wenhui Xie1, Hong Huang1, Shiyu Xiao2, Yong Fan1, Xuerong Deng1, Zhuoli Zhang3. 1. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, No.8, Xishiku Street, West District, Beijing 100034, China. 2. Department of Gastroenterology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. 3. Department of Rheumatology and Clinical Immunology, Peking University First Hospital, No.8, Xishiku Street, West District, Beijing 100034, China. Electronic address: zhuoli.zhang@126.com.
Abstract
INTRODUCTION: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge. OBJECTIVE: To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy. METHODS: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD. RESULTS: 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 immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). 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. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 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 toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33). CONCLUSIONS: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.
INTRODUCTION: Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs), but patients with preexisting autoimmune disease (PAD) have been excluded from clinical trials, leaving serious gaps in knowledge. OBJECTIVE: To evaluate the safety and efficacy of ICIs in PAD patients and cancer and explore the impact of different PAD types and baseline receiving immunosuppressive therapy. METHODS: Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through August 2019 for observational studies reporting safety and efficacy data among ICI-treated patients with cancer and PAD. RESULTS: 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 immune-related adverse events (irAEs) or both of any grade was 60% (95%CI = 52%-68%). 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. Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR = 1.25-1.88). A total of 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 toward lower response rates was observed in patients with baseline immunosuppressants (RR = 0.58, 95%CI = 0.26-1.33). CONCLUSIONS: Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. ICI treatment are also effective in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.