Characteristics and treatment of new-onset arthritis after checkpoint inhibitor therapy

Abstract

Immune checkpoint inhibitors (ICIs) may cause immune-related adverse events (IRAEs). Characterisation and data on treatment of musculoskeletal IRAEs are scarce. In this cohort study, patients receiving ICI therapy who experienced arthralgia were evaluated for the presence of synovitis. Data on demographics, ICI regime, time of onset, imaging and response to therapy of synovitis were prospectively collected. Arthritis was demonstrated in 14 of 16 patients of whom 7 showed monarthritis, 5 had oligoarthritis and 2 had polyarthritis. Patients with ICI-induced arthritis were predominantly male (57%) and seronegative (69%). Regarding the detection of synovitis in staging imaging, moderate sensitivity for contrast-enhanced CT with PET-CT as reference was observed. Disease burden at baseline was high and was significantly reduced after anti-inflammatory treatment. Nine patients were treated with systemic and eight patients with intra-articular glucocorticoids. Six patients who flared on glucocorticoid treatment on tapering were given methotrexate resulting in long-term remission. Patients with synovitis were more likely to have good tumour response. Patients with ICI-induced arthritis were predominantly male and seronegative showing different patterns of arthritis with high disease burden. Good efficacy and safety was observed for methotrexate, particularly for ICI-induced polyarthritis.

Immune checkpoint inhibitor–induced inflammatory arthritis as a model of autoimmune arthritis

“…In another study, the SE allele HLA DRB1*01:01 was found in two out of nine patients who had inflammatory arthritis after treatment with an ICI; however, comparison to a control population was not reported . Interestingly, several studies have shown that SpA‐associated HLA‐B27 alleles do not appear to confer increased risk for ICI‐IA, as almost all patients who developed ICI‐IA were HLA‐B27‐negative . The genetic studies performed thus far show that SE alleles, but not HLA‐B27 alleles, associate with ICI‐IA.…”

“…Thus far, most reports are from small case series or single‐center cohort studies and the assays used to detect seropositivity are not uniform between studies. Despite these limitations, aggregation of the data from multiple studies reveals a low rate of seropositivity among patients developing IA following treatment with ICI therapy with 5.5% (12/217; range 0%‐36%) positive for RF and 5% (11/217; range 0%‐11%) positive for ACPAs . In a study comparing ICI‐IA patients to ethnically matched counterparts with RA, 7.7% of ICI‐IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both .…”

“…While ANA is not specific for a particular subgroup, it does correlate with an increased incidence of JIA‐associated uveitis, particularly iridocyclitis . Aggregate analysis of ANA positivity in patients with ICI‐IA, as defined by a titer greater than 1:40, from several published studies revealed that 15.3% (32/209; range 0%‐89%) of patients were positive for ANA . In addition, antibodies against specific nuclear antigens, dsDNA, Ro, and La (usually seen in patients with systemic lupus erythematosus or Sjögren's syndrome), have been detected in ICI‐IA patients .…”

“…Similar to SpA, patients with ICI-IA have been primarily found to be seronegative for RF and ACPA, 30,31,36,[57][58][59][109][110][111][112] and an indepth analysis of other serologies has not been performed. Thus far, most reports are from small case series or single-center cohort studies and the assays used to detect seropositivity are not uniform between studies.…”

“…Despite these limitations, aggregation of the data from multiple studies reveals a low rate of seropositivity among patients developing IA following treatment with ICI therapy with 5.5% (12/217; range 0%-36%) positive for RF and 5% (11/217; range 0%-11%) positive for ACPAs. 30,31,33,36,[57][58][59]66,[109][110][111][112][113][114][115] In a study comparing ICI-IA patients to ethnically matched counterparts with RA, 7.7% of ICI-IA patients were positive for RF or ACPAs, whereas 64.6% of RA patients were positive for ACPAs and 56.7% positive for RF, with 49.3% being positive for both. 116 Although these results indicate that the prevalence of seropositivity in ICI-IA is much lower than in RA, it is unknown if seropositivity is increased in patients who develop RA-like disease following ICI therapy.…”