Rheumatoid arthritis and polymyalgia rheumatica occurring after immune checkpoint inhibitor treatment.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte-associated protein 4 and programmed cell death protein 1 (PD-1) have demonstrated improved survival for multiple cancers. However, these new drug classes have led to increased immune-related adverse events (IrAE). Rheumatic IrAEs have not been well described in clinical trials. We report here cases of rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR) occurring after ICI treatment. METHODS: This was a retrospective study of patients receiving an ICI in whom symptoms of arthritis or arthralgia developed and revealed a diagnosis of RA or PMR. RESULTS: In 10 patients who received ICI therapy (all anti-PD-1 or anti-PDL1 antibodies), RA or PMR developed at a median of 1 month (1 to 9) after exposure. No patient had pre-existing rheumatic or autoimmune disease. RA developed in six patients; all six were positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies and four for rheumatoid factor. Anti-CCP antibodies were detected in two out of three patients tested before immunotherapy. Disease-modifying antirheumatic drugs were needed for three patients; the three others received corticosteroids or non-steroid anti-inflammatory drugs. PMR was diagnosed in four patients, all responded to corticosteroids. Despite these IrAEs, immunotherapy was pursued for all but one patient until cancer progression. CONCLUSIONS: This is the first description of RA occurring after ICI therapy for cancer. PMR can also occur after ICI, particularly after anti-PD-1 therapy. All cases responded to corticosteroids or with immunosuppressive therapy. Collaboration between rheumatologists and oncologists is crucial and could lead to better recognition and care of these patients.

NKX2.1 mutation revealed by a lymphoid interstitial pneumonia in an adult with rheumatoid arthritis.

This is the first case of a 37-year-old female patient carrier of a heterozygous NKX2.1 mutation associated with RA-ILD with a histological pattern of LIP. This case illustrates the wide panel of ILD subtypes associated with NKX2.1 mutations. https://bit.ly/3F49OTS.

Prevalence of immune-related systemic adverse events in patients treated with anti-Programmed cell Death 1/anti-Programmed cell Death-Ligand 1 agents: A single-centre pharmacovigilance database analysis.

AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)1 a French registry of grade ≥2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia. RESULTS: Out of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjögren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjögren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both). We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57°days (interquartile range (IQR) 24-117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%). CONCLUSION: Although systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted.