Objectives Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs. Methods We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours. Results We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis. Conclusions As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.

Objectives To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults. Design Systematic review and meta-analysis. Setting MEDLINE, CINAHL,Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies. Participants Older adults (aged ≥60 years) who participated in randomized controlled trials that investigated the effectiveness of vitamin D therapy in the prevention of falls and used an explicit fall definition. Measurements Two authors independently extracted data including study characteristics, quality assessment, and outcomes. The I2 statistic was used to assess heterogeneity in a randomeffects model. Results Of 1,679 potentially relevant articles, 10 studies met inclusion criteria. In pooled analysis, vitamin D therapy (200-1000IU) reduced falls by 14% (relative risk [RR] 0.86;95% confidence interval 0.79-0.93;I2=7%) compared to calcium or placebo; number needed to treat=15. The following subgroups had significant fall reductions: community-dwelling (age<80 years), adjunctive calcium supplementation, no history of fractures/falls, duration>6 months, cholecalciferol, and dose≥800 IU. Meta-regression demonstrated no linear association of vitamin D dose or duration with treatment effect. Post-hoc analysis, including 7 additional studies (17 total) without explicit fall definitions, yielded smaller benefit (RR 0.92,0.87-0.98) and more heterogeneity (I2=36%) but found significant intergroup differences favoring adjunctive calcium versus none (p=0.001). Conclusion Vitamin D treatment effectively reduces the risk of falls in older adults. Future studies should investigate whether particular populations or treatment regimens may have greater benefit.

Objective To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of “need for joint replacement surgery,” for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA). Methods New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons’ indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA. Results In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%–12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0–100) + physical function (0–100) > 80]. Conclusion These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define “nonresponders” to disease-modifying drugs in OA clinical trials.

OBJECTIVE-Although patients who develop scleroderma (SSc) later in life (≥ 65 years) may express the entire clinical spectrum of disease, we hypothesize that patients with late-age onset incur a different risk for specific organ manifestations of disease compared to those with youngerage onset SSc.METHODS-In total, 2300 SSc patients were evaluated between 1990-2009 and reviewed from a university-based Scleroderma Center cohort. Demographic profile, SSc subtype, autoantibody status, Medsger severity scores, pulmonary function tests, echocardiography, and right heart catheterization parameters were compared between late-age versus younger-age onset patients.RESULTS-Overall, 2084 (91%) patients developed SSc prior to age 65; whereas 216 (9%) were ≥65 years. Late-age onset patients had a significantly higher proportion of anti-centromere antibodies (42% vs 27%; p=0.001) compared to younger-age onset. Risk of pulmonary hypertension (OR 1.77; 95%CI 1.00, 3.12), muscle weakness (OR 1.85; 95%CI 1.30, 2.64), renal impairment (OR 2.83; 95%CI 1.98, 4.04) and cardiac disease (OR 2.69; 95%CI 1.92, 3.78) was greater among those with late-age onset SSc; although risk of digital ischemia (OR 0.64; 95%CI 0.47, 0.86) was reduced. The cumulative incidence of pulmonary hypertension at 5 years was greater among those with late-age (9%) compared to younger-age (2.5%) onset SSc (log-rank, p<0.001).CONCLUSION-These findings suggest that older SSc patients are at greater risk for pulmonary hypertension, renal impairment, cardiac disease, and muscle weakness. Awareness of the distinct risk for specific organ manifestations in SSc, in particular pulmonary hypertension, should guide the care of older SSc patients whose disease begins after age 65 years.