Cannon, Grant W.

Objective Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre‐existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). Methods All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. Results We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Conclusion Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision‐making and close monitoring.

Objective Immune checkpoint inhibitor (ICI) myositis is a rare but a highly morbid condition, particularly with the ICI myositis triad syndrome of myositis, myocarditis, and myasthenia gravis. We report the clinical characteristics of ICI myositis and all‐cause mortality in these patients. Methods We performed a national retrospective cohort study of US veterans treated with an ICI between June 2011 and February 2022. Cases were identified by elevated creatinine kinase (CK) following ICI therapy and/or “myositis” in notes. Chart review determined if candidates had ICI‐associated myositis and were subsequently classified as isolated ICI myositis or ICI triad syndrome. Results Of 29,296 veterans treated with ICIs, 68 (0.2%) ICI‐induced myositis cases were identified, including 23 patients with ICI triad syndrome and 45 patients with isolated ICI myositis. Median survival duration for ICI triad syndrome was 2.5 (95% confidence interval [CI] 1.7–18.5) months in comparison to 20.4 (95% CI 6.2–60) months for isolated ICI myositis and 12.6 (95% CI 12.3–12.8) months median survival for patients treated with ICI without myositis. Patients with ICI triad syndrome had 60.0% mortality during the six months following initiation of ICI treatment, in comparison to 30.2% mortality in isolated ICI myositis and 31.5% mortality in patients without myositis. Six months after the first ICI treatment, subsequent mortality trends were similar in the three groups. Conclusion ICI triad syndrome is associated with higher overall mortality and shortened median survival times during the first six months after initial ICI therapy, whereas isolated ICI myositis is associated with similar mortality outcomes compared to patients treated with ICI who did not develop myositis. image

Objective The aim of this study was to determine whether pollutants such as fire smoke–related particulate matter <2.5 μm (PM 2.5 ) are associated with incident rheumatoid arthritis (RA) and RA‐associated interstitial lung disease (RA‐ILD). Methods This patient–control study used Veterans Affairs (VA) data from October 1, 2009, to December 31, 2018. We identified patients with incident RA and RA‐ILD using validated algorithms, matching each patient to ≤10 controls on age, sex, and VA enrollment year. We obtained pollutants including fire smoke PM 2.5 , carbon monoxide, nitrogen oxides (NOx), ozone, overall PM 2.5 , PM 10 , and sulfur dioxide (SO 2 ) at least one year before the index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for incident RA and RA‐ILD, adjusted for confounders. Results We identified 9,701 patients with incident RA (mean age 65 years, 86% male), including 531 patients with RA‐ILD (mean age 69 years, 91% male), and 68,852 matched controls. Fire smoke PM 2.5 was not associated with RA (aOR 1.07, 95% CI 0.92–1.23) but was associated with RA‐ILD (aOR 1.98, 95% CI 1.08–3.62, per 1 μg/m 3 ). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06–1.27, highest vs lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06–1.34) and PM 10 (aOR 1.25, 95% CI 1.10–1.43) were associated with seronegative RA. Carbon monoxide, overall PM 2.5 , and SO 2 were not, or negatively, associated with RA and RA‐ILD. Conclusion Increased fire smoke PM 2.5 was associated with RA‐ILD, whereas NOx, ozone, and PM 10 were associated with RA risk. Thus, air pollution may increase the risk of RA and RA‐ILD. image

ObjectiveWe aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA‐interstitial lung disease (ILD).MethodsWe performed a retrospective, matched cohort study of RA and RA‐ILD within the Veterans Health Administration (VA) between 2000 and 2019. Patients with RA and RA‐ILD were identified with validated administrative‐based algorithms, then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identified from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed.ResultsWe matched 72,795 patients with RA with 633,937 patients without RA (mean age 63 years; 88% male). Over 4,481,323 patient‐years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (adjusted hazard ratio [aHR] 1.58 [95% confidence interval (CI) 1.52–1.64]), which persisted in never smokers (aHR 1.65 [95% CI 1.22–2.24]) and in those with incident RA (aHR 1.54 [95% CI 1.44–1.65]). Compared to non‐RA controls, prevalent RA‐ILD (n = 757) was more strongly associated with lung cancer risk (aHR 3.25 [95% CI 2.13–4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51–1.64]). Analyses of both prevalent and incident RA‐ILD produced similar results (RA‐ILD vs non‐RA aHR 2.88 [95% CI 2.45–3.40]).ConclusionRA was associated with a >50% increased risk of lung cancer, and those with RA‐ILD represented a particularly high‐risk group with an approximate three‐fold increased risk. Increased lung cancer surveillance in RA, and especially RA‐ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death.

Abstract B10.Ek alpha transgenic mice were mated with H2-E B10.Q and SWR mice. F1 and F1 x parental strain backcross progeny were tested for arthritis and autoimmune reactivity to mouse type II collagen (MII) after immunization with bovine, chick, deer, or human type II collagen. The results were correlated with the H-2 haplotype (b/q vs q/q) and the TCR V beta profile of peripheral blood T cells in each mouse. Hybrid progeny expressed TCR profiles different from either parent because of the TCR V beta genomic deletions of SWR mice (V beta a), the wild-type TCR allele of C57Bl/10 (B10) mice (V beta b), and the intrathymic negative selection processes resulting from cell surface expression of Ek alpha-A q beta or Eb beta-Ek alpha, together with the integrated retroviral genes Mtv-9 originating in B10 mice and Mtv-7 (Mls-1a) from SWR mice. (B10.Ek alpha x SWR)F1 mice developed higher IgG anti-MII Ab titers, but much milder arthritis than (B10.E x B10.Q)F1 mice. Expression of Ek alpha did not change the level of IgG anti-MII Ab nor the degree of susceptibility to collagen-induced arthritis (CIA) in the H-2q/q and H-2b/q progeny of (B10.Ek alpha x B10.Q)F1 x B10.Q matings, indicating that the Mtv-9-reactive, TCR V beta 5+, and V beta 11+ T cells are not critical to CIA. Among bovine type II collagen-immunized (B10.Ek alpha x SWR)F1 x SWR backcross mice: 1) arthritis severity is associated with the presence of V beta b (p &lt; or = 0.01) and expression of Ek alpha (p &lt; or = 0.05), but not with the MHC haplotype (b/q vs q/q); 2) regression analysis showed a significant association (R = 0.99) between IgG anti-MII Ab titers and the level of Mtv-7-reactive V beta 6+ T cells that was detectable in the IgG1, but not the IgG2a subclass. The data prompt the speculation that Mtv-7-reactive V beta 6+ (or V beta 7+) T cells in (B10.EK alpha x SWR)F1 x SWR mice express Th2-type properties, and thus contribute to the combination of mild arthritis but high anti-MII Ab titers that characterize mice of SWR heritage.