PracticeUpdate: Dermatology & Rheumatology

ACR 2016 23

injection of SM04690 than placebo achieved a significant OMERACT-OARSI strict response, a composite score of clinical efficacy requiring both absolute and relative improvement,” he said. “Through further analysis, we saw that the clinical response was driven by improvements in both pain and function measurements from baseline at 12 and at 24 weeks, not solely by pain or function measurement, suggesting clinically relevant, multidimensional improvement.” The researchers also explored the potential efficacy of Wnt inhibitors on joint space narrowing and cartilage loss, two signs of worsening arthritis. “A therapy with the potential to not only decrease pain and improve function for patients with knee osteoarthritis, but also to halt or reverse processes driving disease progression, would be a welcome addition to the osteoarthritis treatment armamentarium,” said Dr Yazici. The researchers examined their data to evaluate the change from baseline in joint space width (JSW) on x-rays, and then conducted an analysis of JSW change using repeated measures analysis of covariance (ANCOVA), adjusting for baseline JSW in the modified intention-to-treat (mITT) population. In the mITT population at 24 weeks, subjects in the 0.07 mg cohort showed a statistically significant increase in mean medial JSW of 0.49 ± 0.75 mm, P = 0.02, from baseline versus placebo. No change in mean medial JSW was observed in the 0.03 mg cohort (mean 0.00 ± 0.69 mm), a decrease in mean medial JSW of 0.15 ±1.07 mm in the 0.23 mg cohort, and a mean decrease of 0.33 ± 0.87 mm observed in the placebo cohort. “These results, based on exploratory x-ray outcomes, suggest that treatment with SM04690 may maintain or increase joint space width compared to placebo,” said Dr Yazici. “SM04690 offers a novel mechanism of action, and the findings so far suggest that it is safe and has the potential for true disease modification, as well as relief of signs and symptoms of osteoarthritis after a single injection,” he said. “Radiographs taken at baseline and at 24 weeks post injection suggested that mean joint space width was maintained in one dose, and even increased in another dose.” “The next steps are to further assess the safety and efficacy of Wnt inhibitors,” said Dr Yazici. The researchers are conducting a phase 2 trial on patients with moderate to severe knee osteoarthritis. “Most importantly, we hope SM04690 will continue to exhibit positive safety and efficacy so the millions of patients with knee osteoarthritis can avail themselves of new treatment option,” he said.

Patients with RA at comparable CV event risk as those with type 2 diabetes Rheumatoid arthritis is associated with serious risk of cardiovascular events. Over a 15-year period, patients with rheumatoid arthritis have been shown to be at double the risk of these events as those in the general population. These rates are similar to those associated with type 2 diabetes, results of a retrospective database analysis show. M ichael T. Nurmohamed, MD, PhD, of Vrije Universiteit Amsterdam, diabetes than for the cohort from the general population.

Increased risk of heart attacks or strokes among people with established rheumatoid arthritis was found to be comparable to patients with type 2 diabetes. The increased risk in patients with rheumatoid

The Netherlands, set out to learn more about the causes of increased mortality among patients with rheumatoid arthritis, and the severity of their risk.

arthritis, even after adjusting for traditional heart disease risk factors, remained elevated by as much as 70% compared to the cohort from the general population. The findings indicated that chronic, systemic inflammation in rheumatoid arthritis contributes independently to cardiovascular risks. Dr Nurmohamed said, “In rheumatoid arthritis, cardiovascular risk management is needed, as in diabetes. Patients and their rheumatologists need to be attentive to this risk and cardiovascular risk management in patients with rheumatoid arthritis should target disease activity as well as traditional cardiovascular risk factors. Unfortunately, preventive measures against cardiovascular disease are poorly implemented.” He noted that effective treatment of systemic inflammation may address the increased risk of cardiovascular events and their attendant higher mortality risk. Dr Nurmohamed concluded, “Evidence is accumulating that biologics reduce cardiovascular risk in rheumatoid arthritis. The strategy of tapering biologics, however, might expose our patients to increased cardiovascular risk. We aim to conduct mechanistic studies in this issue.” Improvement of current cardiovascular risk prediction models by adding relevant biomarkers may also help rheumatologists better identify which patients with rheumatoid arthritis are u most at risk of cardiovascular events and why. Such identification may lead to effective interventions.

He remarked, “In daily clinical practice, it seemed that patients with rheumatoid arthritis suffered from myocardial infarctions more frequently than people in the general population. We started this study more than 15 years ago, when only sparse data were available on cardiovascular morbidity in rheumatoid arthritis. The teamused data fromtheCARdiovascular research and RhEumatoid arthritis (CARRE) Study, a prospective cohort study whose aim is to investigate cardiovascular risk factors in a random sample of 353 patients with long-term rheumatoid arthritis. They assessed heart disease-related events after 3, 10, and 15 years of follow-up. They compared findings from these patients with rheumatoid arthritis with data on glucose metabolism and cardiovascular risk factors from the Hoom study of 2540 persons in the general population. Risk of cardiovascular events for patients with established rheumatoid arthritis was more than double that of the general population. Ninety-six patients with rheumatoid arthritis suffered a cardiovascular event during 2703 person-years of follow-up, an incidence rate of 3.6 per 100 person-years. In the general population cohort, 298 individuals experienced a cardiovascular event during a follow-up of 25,335 person- years, an incidence rate of 1.4 per 100 person-years. Of those 298 patients, 41 had diabetes mellitus. Age- and sex-adjusted hazard rates for cardiovascular events were higher for both rheumatoid arthritis and

DECEMBER 2016