Background/Purpose: Immune checkpoint inhibitors (ICI) against CTLA-4 or PD- 1/PD-L1 and more recently TIM3,  have demonstrated efficacy in improving the survival of patients with diverse advanced malignancies including melanoma, lung and urothelial cancer, among others.

Because of its mechanism of action, ICI are prone to produce different immune-related adverse events (irAEs), including musculoskeletal manifestations.

Our aim was to describe the experience with rheumatic irAEs in three tertiary centers.

Methods: All adult patients referred to the rheumatology departments of three tertiary centers from 2015 to 2018 because of the onset of musculoskeletal symptoms following treatment with an ICI were included.

Data collected comprised demographic features as well as ICI indication and type, history of rheumatic disease, musculoskeletal manifestations at the irAE onset, laboratory tests, ultrasound findings and treatment. Diagnostic and treatment approach was done according to clinical judgment in daily clinical practice settings.

Results: 38 patients were included, 39.5% female, mean age was 64 years (range 32-83). The indication for ICI was lung cancer in 20 cases,  10 melanoma, 3 urothelial and 1 for acute myeloid leukemia, squamous skin, breast, head and neck and rectum cancer.

Pembrolizumab was the most used ICI with 17 cases (1 combined with epacadostat), 12 were treated with Nivolumab (4 combined with Ipilimumab), 6 Atezolizumab (1 combined with Ibatasertib) whereas Durvalumab, Ipilimumab and MBG453 ( a TIM3 inhibitor) were used each in 1 patient.

A history of rheumatic disease was reported in 12 patients 3 gout, 2 chondrocalcinosis and 1 case for each RA, Spondyloarthritis, SLE, psoriasis, fibromyalgia and osteoarthritis.

The most frequent irAE presentations were arthritis with 20 cases (52.3%) and arthralgia in 12 cases (31.6%). After the assessment, 15 patients were diagnosed as undifferentiated arthritis, 4 psoriatic-like arthritis,  2 PMR-like,1 leukocytoclastic vasculitis, 1 small-vessel vasculitis, 1 tenosynovitis, 2 gout and 12  were classified as having non-inflammatory symptoms.

Antibody status was analyzed in 33 patients, ACPA were positive in 1 patient with known RA, ANAs were positive in 4 (including 1 patient with previous SLE) but without any specificities (i.e. ENAs) and ANCA were negative in one case with small-vessel vasculitis.

Ultrasonography assessment was performed in 11 patients, 3 did not show signs of inflammation. Among the remaining ones, 6 presented either synovial hypertrophy with/or positive power Doppler, 1 a peritendinous fluid collection and 1 an elbow joint effusion.

Most patients were treated with glucocorticoids and NSAID 23 (60.5%) and 13 (34.2%) respectively. Only 4 patients required csDMARD (Methotrexate or Hydroxychloroquine) and 4 had to withdraw ICI treatment due to irAEs.

Conclusion: Our results were in line with previous studies showing that MSK-irAEs associated with ICI may present as a flare of a previous known rheumatic disease or as a de novo symptom.

Most patients presented with asymmetric mono or oligoarthritis and responded to GC and NSAID with only a few requiring DMARD or ICI withdrawal

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatic-immune-related-adverse-events-associated-with-treatment-with-immune-checkpoint-inhibitors-a-multicenter-study-of-38-cases/