Inflammatory arthritis (IA) is the most common rheumatic adverse event seen in people on immune checkpoint inhibitor (ICI) therapy and can largely be managed by rheumatologists without the need to halt cancer treatment, according to Michael D. Richter, MD, of the Mayo School of Graduate Medical Education, Rochester, Minn., and his colleagues.
Dr. Michael D. Richter
The investigators’ observations of patients seen at the Mayo Clinic over a 7-year period suggested that “IA should not be seen as a contraindication to continuing or restarting ICIs, ” although continuing ICI therapy concurrently with high-dose steroids is “generally not recommended.” Previous estimates of rheumatic adverse events with ICIs had ranged from 1% to 10%, and management had largely been based on the experience of experts and findings from retrospective studies, they noted.
“This study aims to add granularity to the existing literature by describing the prevalence, clinical characteristics, and treatment outcomes of a large, single-institution cohort of patients with rheumatic immune-related adverse events,” Dr. Richter and his associates wrote in an article published in Arthritis & Rheumatology.
The analysis included 1,293 patients who had received treatment with any ICI at the Mayo Clinic between January 2011 and March 2018. Patients who had received treatment at other centers but were seen at the Mayo clinic for their rheumatic adverse event were also included.
Overall, 61 patients experienced a rheumatic immune-related adverse event (Rh-irAE) related to checkpoint inhibitor treatment; 43 were from the Mayo cohort and 18 were from other centers. The average age of the patients was 62.6 years, and almost half (49%) were female.
New-onset inflammatory arthritis was the most common Rh-irAE reported (n = 34), with the majority of patients presenting with polyarticular symptoms (n = 22; 65%).
Most of these patients were managed by a rheumatologist and were treated with systemic glucocorticoids (n = 26; 76%) for an average duration of 18 weeks. Five of the patients also required disease-modifying antirheumatic drugs and eight needed NSAIDS or intra-articular steroids.
The investigators noted that almost half of the patients (47%) experienced a complete resolution of symptoms during the study period, although few achieved this while they were still on the cancer treatment.
According to the investigators, the clinical characteristics of IA in their cohort support the existing literature: “Time of symptom onset is generally 4-8 weeks after starting ICI therapy. … The majority of patients require long courses of systemic glucocorticoids. And very few achieve complete symptom resolution while continuing ICI therapy,” they wrote.
The database analysis also revealed that a further 10 patients developed myopathy, with all patients presenting with myalgias and weaknesses. Five had bulbar myopathy, and four patients were diagnosed with concomitant myocarditis. All of these patients were treated with glucocorticoids for an average treatment duration of 15 weeks.
Complete resolution of the myopathy was observed in 70%, but two patients died from complications related to myocarditis and bulbar myopathy.
Other rheumatic events included four cases of vasculitis and four cases of polymyalgia rheumatica and six cases of diffuse systemic sclerosis or sicca syndromes.
“In lieu of controlled prospective studies, this cohort may serve as a guide for rheumatologists managing and counseling patients with Rh-IrAEs,” the investigators concluded.
“It remains unclear why some patients develop Rh-irAEs, and so far no genomic risk factors have been identified, though the varied clinical phenotypes of Rh-irAEs certainly suggest multiple underlying immunopathogenic mechanisms. Further prospective studies that distinguish between subsets of Rh-irAEs are necessary to better understand their pathophysiology and improve clinical care,” they added.
They noted that a limitation of the study was its reliance on retrospective data and clinician diagnoses.
None of the authors declared any financial or other conflicts of interest.
SOURCE: Richter MD et al. Arthritis Rheumatol. 2018 Oct 3. doi: 10.1002/art.40745.