ICI-induced rheumatic irAEs respond to biologics

Biologics such as interleukin-6 receptor (IL-6R) blockers may have a role in management of immune checkpoint inhibitor (ICI)-induced rheumatic immune-related adverse events (irAEs) in cancer patients, according to a small French study.

Use of agents such as tocilizumab may help patients avoid long term use of glucocorticoids or cessation of checkpoint inhibitor therapy, the study authors suggested.

Their study, published in RMD Open [link here], comprised 20 patients with irAEs associated with mainly nivolumab or pembrolizumab treatment for conditions including lung cancer and melanoma.

Patients were experiencing RA-like (80%), PMR-like (10%) or PsA-like (10%) inflammatory arthritis including flare of a pre-existing RA in two cases.

Most patients (95%) were treated with glucocorticoids as first-line therapy and 60% had previously received the csDMARD methotrexate for their irAEs.

The study found the IL-6R therapy tocilizumab was prescribed for 60% of patients. Another IL-6R agent sarilumab, TNF inhibitors adalimumab, etanercept and infliximab, along with anakinra, baricitinib and ustekinumab were also prescribed.

“ICI was discontinued permanently in 12/20 patients (60%) due to the rheumatic irAE (n=10) or another toxicity (n=2), and temporarily in 5/20 patients (25%).”

“Overall, the use of bDMARD or JAKi led to complete (7/20; 35%) or partial (10/20; 50%) resolution of the rheumatic irAE and glucocorticoids were stopped (6/20, 30%) or reduced (7/20; 35%) following bDMARD initiation,” the study authors said.

The median duration of TNFi or anti-IL-6R use was 30 weeks in patients with good oncological outcomes and 17 weeks in patients with cancer progression.

The study investigators said glucocorticoids were recommended as first-line therapy in all guidelines for management of irAEs and the use of bDMARDs or JAK inhibitor appeared scarce.

However there were concerns about their potential impact on tumour response, notably with dosage >10 mg/day of prednisone equivalent.

“Indeed, owing to encouraging preclinical data and ongoing oncological trials, one may discuss the use of targeted therapy, mainly bDMARD, earlier in the management of rheumatic irAE to avoid long-term use of glucocorticoids. This approach is also discussed in patients with pre-existing autoimmune disease by preferring targeted therapies to non-selective immunosuppressive therapies at ICI initiation.”

The study authors said the reasons for choosing a specific DMARD were largely unknown although concomitant colitis or pneumonitis in some patients may have been a factor in the choice of an anti-IL-6.

The investigators said their study supports the need for clinical trials evaluating the use of anti-IL-6R therapy and its optimal timing in the management of rheumatic irAEs.

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