BACKGROUND: Internet-delivered exercise, education, and pain coping skills training is effective for people with knee osteoarthritis, yet it is not clear whether this treatment is better suited to particular subgroups of patients. OBJECTIVE: The aim was to explore demographic and clinical moderators of the effect of an internet-delivered intervention on changes in pain and physical function in people with knee osteoarthritis. METHODS: Exploratory analysis of data from 148 people with knee osteoarthritis who participated in a randomized controlled trial comparing internet-delivered exercise, education, and pain coping skills training to internet-delivered education alone. Primary outcomes were changes in knee pain while walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index function subscale) at 3 and 9 months. Separate regression models were fit with moderator variables (age, gender, expectations of outcomes, self-efficacy (pain), education, employment status, pain catastrophizing, body mass index) and study group as covariates, including an interaction between the two. RESULTS: Participants in the intervention group who were currently employed had significantly greater reductions in pain at 3 months than similar participants in the control group (between-group difference mean 2.38, 95% CI 1.52 to 3.23 numerical rating scale units; interaction p = 0.02). Additionally, within the intervention group, pain at 3 months reduced by mean 0.53 (95% CI 0.28 to 0.78) numerical rating scale units per unit increase in baseline self-efficacy for managing pain compared to mean 0.11 numerical rating scale units (95% CI -0.13 to 0.35; interaction p = 0.02) for the control group. CONCLUSIONS: People who were employed and had higher self-efficacy at baseline were more likely to experience greater improvements in pain at 3 months after an internet-delivered exercise, education, and pain coping skills training program. There was no evidence of a difference in the effect across gender, educational level, expectation of treatment outcome, or across age, body mass index, or tendency to catastrophize pain. Findings support the effectiveness of internet-delivered care for a wide range of people with knee osteoarthritis, but future confirmatory research is needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614000243617; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365812&isReview=true.

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