PURPOSE: The aim was to evaluate whether neck-specific exercise, with (NSEB) or without (NSE) a behavioural approach, improves health-related quality of life (HRQoL) compared to physical activity prescription (PPA) in chronic whiplash-associated disorders (WAD) grades 2 and 3. A secondary aim was to identify factors associated with HRQoL and HRQoL improvement following exercise interventions. METHODS: This is a secondary analysis of a multicentre randomized clinical trial. Participants (n = 216) with chronic WAD grades 2 and 3 were randomized to 12 weeks of PPA or physiotherapist-led NSE or NSEB. The EQ-5D 3L/EQ-VAS and SF-36v2 physical (PCS) and mental (MCS) component summaries were collected together with several neck-related and psychosocial outcomes at baseline, after 3, 6 and 12 months, and were analysed with linear mixed models (all time points) and multivariate linear regressions (baseline, 6 months). RESULTS: NSE/NSEB resulted in better outcomes than PPA (EQ-VAS and SF-36 PCS, both groups, p < 0.01) but not in a higher EQ-5D score. Improvement over time was seen in EQ-5D/EQ-VAS for the NSEB group (p < 0.01), and for NSE/NSEB as measured with the PCS (p < 0.01). Factors associated with baseline HRQoL and change to 6 months in HRQoL (R(2) 0.38 to 0.59) were both neck-related and psychosocial (eg, depression, work ability). CONCLUSION: Neck-specific exercise, particularly with a behavioural approach, may have a more positive impact on HRQoL than physical activity prescription in chronic WAD grades 2 and 3. HRQoL is however complex, and other factors also need to be considered. Factors associated with HRQL and improvements in HRQoL following exercise are multidimensional. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT01528579.

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