Sabrina Hoa1, Linda Laaouad2, Janet Roberts3, Daniel Ennis4,5, Carrie Ye6, Karam Al Jumaily6, Janet Pope7, Tatiana Nevskaya7, Alexandra Saltman5, Megan Himmel5, Robert Rottapel5, Christina Ly8, Ines Colmegna8, Aurore Fifi-Mah9, Nancy Maltez10, Annaliese Tisseverasinghe11, Marie Hudson8, Shahin Jamal4. 1. Division of Rheumatology, Centre hospitalier de l'Université de Montréal, E-514, 264 boul. René-Lévesque East, Montreal, QC, H2X 1P1, Canada. sabrina.hoa@mail.mcgill.ca. 2. Division of Rheumatology, Centre hospitalier de l'Université de Montréal, E-514, 264 boul. René-Lévesque East, Montreal, QC, H2X 1P1, Canada. 3. Division of Rheumatology, Dalhousie University, Halifax, NS, Canada. 4. Division of Rheumatology, University of British Columbia, Vancouver, BC, Canada. 5. Division of Rheumatology, University of Toronto, Toronto, ON, Canada. 6. Division of Rheumatology, University of Alberta, Edmonton, AB, Canada. 7. Division of Rheumatology, University of Western Ontario, London, ON, Canada. 8. Division of Rheumatology, McGill University, Montreal, QC, Canada. 9. Division of Rheumatology, University of Calgary, Calgary, AB, Canada. 10. Division of Rheumatology, University of Ottawa, Ottawa, ON, Canada. 11. Division of Rheumatology, University of Manitoba, Winnipeg, MB, Canada.
Abstract
BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.
BACKGROUND: Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD). METHODS: Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form. RESULTS: Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0-17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs. CONCLUSION: PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.
Authors: José A Gómez-Puerta; David Lobo-Prat; Carolina Perez-García; Andrés Ponce; Beatriz Frade-Sosa; Ana Milena Millán Arciniegas; Fabiola Ojeda; Virginia Ruiz-Esquide; Hector Corominas Journal: Front Med (Lausanne) Date: 2022-06-15