OP0004 Rheumatoid arthritis occuring after immune checkpoint inhibitors

• Published in: Annals of the rheumatic diseases Vol. 76; no. Suppl 2; p. 51
• Main Authors: Belkhir, R, Burel, S Le, Lambotte, O, Mouterde, G, Pertuiset, E, Dunogeant, L, Marabelle, A, Leary, A, Voisin, A-L, Mariette, X
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2017
• Subjects: Adenocarcinoma; Apoptosis; Autoantibodies; Cancer; Cell death; Corticosteroids; CTLA-4 protein; Cytotoxicity; Endometrium; Hydroxychloroquine; Immune checkpoint; Immune checkpoint inhibitors; Immunological diseases; Immunosuppressive agents; Inflammation; Lung cancer; Lymphocytes T; Melanoma; Metastases; Metastasis; Methotrexate; Monoclonal antibodies; Nonsteroidal anti-inflammatory drugs; Patients; PD-1 protein; Prednisone; Rheumatic diseases; Rheumatoid arthritis; Rheumatology; Sjogren's syndrome; Squamous cell carcinoma; Targeted cancer therapy; Vagina
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2017-eular.3768

BackgroundImmune checkpoints inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1) have demonstrated survival improvement in multiple cancers. Immune Related Adverse Events (IrAE) have been described with ipilimumab and anti PD1. Relapse or flare of preexisting auto-immune diseases has been reported but occurrence of new auto-immune diseases seems to be less frequent. A series of 13 patients with non-classified rheumatic IrAE has been published: 9 patients developed non-specific inflammatory arthritis but no seropositive rheumatoid arthritis (RA) and 4 presented with sicca symptoms but did not fulfill criteria for Sjögren syndrome [1].ObjectivesWe did a retrospective study for collecting patients who developed seropositive rheumatoid arthritis (RA) after exposition to ICIs.MethodsWe used the “Club Rhumatismes et Inflammation (CRI)” network, a section of the French Society of Rheumatology and the Gustave Roussy Cancer Center register of safety of ICI for collecting patients treated with an ICI and who developed symptoms of arthritis with diagnosis of RA.ResultsWe report 6 patients without any previous rheumatic disease, who developed seropositive rheumatoid arthritis (RA) after exposition to ICIs, all of them after anti-PD1.Table 1PatientsSex/ageType of cancerICIDate of first ICI exposureDate of IrAEType of rheumatic IrAEIrAE response to treatmentAutoantibody results 1F 55 ySquamous cell carcinoma ofnivolumabOctober 2015October 2015RAresolution with NSAIDSanti-CCP: 671 U/mlthe vaginaRF: 18 UI/ml2F 66 yEndometrial adenocarcinomapembrolizumabMarch 2016April 2016RAresolution with corticosteroidsanti-CCP: 233 U/mlprednisone 10 mg/dayRF:180 UI/ml3M 59 yLung adenocarcinomanivolumabMay 2016July 2016RAresolution with prednisone 10 mg/danti-CCP: 61 U/mltapered to 5 mg/d 1 months laterRF: 47 UI/ml4F 56 yMetastatic melanomapembrolizumabAugust 2015September 2015RAresolution with hydroxychloroquineanti-CCP: 22UI/ml400mg/day and NSAIDS5M 80 yMetastatic melanomanivolumabApril 2016April 2016RAResolution with prednisone 15mg/day (tapered)anti-CCP:42 UI/mland hydroxychloroquine 200mg/day6M 68 yLung adenocarcinomanivolumabJune 2015July 2015RAResolution after stopping nivolumab and afteranti-CCP >300U/ml1 month of methotrexate 10 mg/w (maintained 3 months)RF: 246 UI/mlConclusionsThis is the first description of RA occurring after anti-PD1 treatment for cancer. All cases responded to corticosteroids or with immunosuppressive therapy. This suggests that the PD1/PDL1 axis plays a role in RA pathophysiology. The combined expertise of oncologists, immunologists and rheumatologists is crucial in the successful management of these patients.References Cappelli LC, Gutierrez AK, Baer AN, et al. Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab. Ann Rheum Dis 2017;76:43–50. Disclosure of InterestNone declared