Objective. To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities. Methods. In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ‡30 kg/m 2 ), with severity score ‡2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training and training of daily activities. The control group received their current medical care for knee OA and were placed on a waiting list for exercise therapy. Primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index, subscale physical functioning (WOMAC-pf), and the 6-minute walk test (6MWT). Measurements were performed at baseline, after 20 weeks (directly posttreatment), and at 3 months posttreatment. Results. Statistically significant physical functioning differences over time were found between the intervention and control group (WOMAC: B 5 27.43 [95% confidence interval (95% CI) 29.99, 24.87], P < 0.001; and 6MWT: B 5 34.16 [95% CI 17.68, 50.64], P < 0.001) in favor of the intervention group. At 3 months followup, the mean improvements in the intervention group were 33% on the WOMAC scale and 15% on the 6MWT. These improvements are of clinical relevance. No serious adverse events occurred during the intervention. Conclusion. This is the first study showing that tailored exercise therapy is efficacious in improving physical functioning and safe in patients with knee OA and severe comorbidities.
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