Blood cancers

Cases suggest immune checkpoint inhibitors may trigger RA

Collaboration between haematologists and rheumatologists is needed to detect and manage autoimmune rheumatic conditions that may be triggered by immunotherapy drugs, researchers say.

French clinicians have reported a series of 10 patients who developed rheumatoid arthritis or polymyalgia rheumatica (PMR) after treatment with immune checkpoint inhibitors (ICI) for a range of cancers.

They found rheumatoid arthritis developed in six patients within one to nine months – all of whom were positive for anti-cyclic citrullinated peptide (CCP) antibodies and four for rheumatoid factor.

According to the report, none of the patients had pre-existing rheumatic or autoimmune disease.

While checkpoint inhibitors have been previously reported to cause flare or relapse in pre-existing autoimmune disease, the authors said this was the first description of seropositive rheumatoid arthritis occurring in patients receiving immunotherapy.

“The short time between ICI treatment and the development of joint symptoms and anti-CCP positivity before ICI therapy in 2/3 patients suggested that some of these patients had a pre-RA status and that the treatment with ICI may have triggered the clinical disease.”

All cases occurred after PD-1 inhibition and not anti-CTLA-4 antibody treatment.

The authors warned that many milder cases were probably managed with NSAIDs or corticosteroids and not referred to rheumatologists for inclusion in the series.

“Because rheumatic IrAEs are closely linked to the mechanism of action of ICI on immune cells, we can expect many rheumatic IrAEs or exacerbation of rheumatic IrAEs considering the future worldwide prescription of ICI.”

However the report contrasts with an Australian series of 18 patients with musculoskeletal immune adverse events after checkpoint inhibitor treatment.

According to Correspondence in the Annals of Rheumatic Disease, none of the patients seroconverted and none had clinical features suggestive of rheumatoid arthritis.

“In addition to the negative serology, MRI of affected joints failed to identify synovial hypertrophy to suggest the start of pannus formation.”

Professor Manolios

Co-author Professor Nicholas Manolios, from Westmead Hospital and the University of Sydney, told the limbic more experience with the drugs was required to fully understand what was going on.

““We’’re not sure whether these drugs allow something that’’s been held down to come to the surface or whether they just form arthritis like everybody else. There is not enough evidence to know which is which.””

He suggested other factors such as different smoking rates might help explain the different experiences.

““I’’m just trying to explain their observation and our observation. They have rheumatoid factor and are calling it rheumatoid arthritis but we don’t see rheumatoid factor. So what is the difference in the patients?””

Both groups of patients responded well to treatment with NSAIDS, steroids or DMARDs. Most patients were also able to continue with immunotherapy for their cancer.

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