Background: Low-dose radiation therapy is commonly used as treatment for benign diseases, including osteoarthritis, in some countries (eg, Germany). We have previously presented our 3-month follow-up results of two randomised sham-controlled trials, in which no substantial effects of low-dose radiation therapy on clinical outcomes were seen in patients with knee and hand osteoarthritis. Here we report the 6-month and 12-month results of these studies.
Methods: In one randomised sham-controlled trial, patients with knee osteoarthrosis were recruited, and in the other trial patients with hand osteoarthritis were recruited. All patients were recruited from the department of rheumatology of Sint Maartenskliniek (Nijmegen, The Netherlands) and the trials were undertaken in parallel. Patients were eligible if they had knee or hand osteoarthritis according to American College of Rheumatology (ACR) criteria, had a pain score of 5 or more on a 0-10 scale for at least 15 of the past 30 days, and did not meet 2011 modified ACR criteria for fibromyalgia. In each study, patients were randomly assigned (1:1), stratified by pain score (<8 vs ≥8) using a computer-generated randomisation list and stratified block randomisation, to low-dose radiation therapy (six fractions of 1 Gy low-dose radiation therapy in 2 weeks) or sham (six sessions with 0 Gy of radiation therapy in 2 weeks) intervention. Patients and researchers involved in patient contact or assessments were masked to group allocation, whereas the radiotherapy technologist who did the treatment was unmasked. Patients completed questionnaires (numeric rating scale of patients' global assessment and validated measures for pain and functioning) at baseline and at 1, 2, 3, 6, and 12 months after starting treatment. The primary outcome was the proportion of participants who responded according to the Outcome Measures in Rheumatology Osteoarthritis Research Society International responder criteria at 3 months, which has been reported previously. Here we report the proportion of participants who responded at 6 months and 12 months, and other clinical outcomes of pain, functioning, and patients' global assessment of their symptoms. We used logistic and linear mixed-models analyses to assess differences in number of responders and continuous outcomes. Safety was assessed in all participants who received at least one fraction of low-dose radiation or sham treatment. This study is registered with the Netherlands Trial Registry, NTR4574, and is closed to accrual.
Findings: Between Oct 14, 2015, and May 3, 2017, 213 patients were screened for inclusion for the knee osteoarthritis study, of whom 55 were eligible and randomly assigned to low-dose radiation therapy (n=27) or sham intervention (n=28). In parallel, for the hand osteoarthritis study, 368 patients were screened and 56 were randomly assigned low-dose radiation (n=28) or sham intervention (n=28). Some minor imbalances in baseline demographic characteristics in terms of sex and age were seen in both the knee and hand cohorts. In the knee osteoarthritis cohort, 48 patients were assessible at 6 months and 50 were assessible at 12 months, and in the hand osteoarthritis cohort 52 patients were assessible at 6 and 12 months. We found no significant differences at 6 or 12 months in the proportion of participants who had a response for both groups. In the knee osteoarthritis group, at 6 months, the number of responders was nine (41%) of 22 patients who received low-dose radiation therapy versus nine (35%) of 26 patients who received the sham intervention (difference in proportion 7% [95% CI -20 to 33]; odds ratio [OR] 1·34 [95% CI 0·41 to 4·42]); and at 12 months, 13 (52%) of 25 patients versus 11 (44%) of 25 patients responded (difference in proportion 8% [-19 to 35]; OR 1·41 [0·45 to 4·48]). In the hand osteoarthritis group, at 6 months, the number of responders was seven (28%) of 25 patients who received low-dose radiation therapy versus 11 (31%) of 27 patients who received the sham intervention (difference in proportion 12% [-38 to 13]; OR 0·57 [0·18 to 1·81]); and at 12 months, eight (31%) of 26 patients versus seven (27%) of 26 patients responded (difference in proportion 4% [-20 to 29]; OR 1·23 [0·37 to 4·12]). We did not find any difference between groups in other clinical outcomes at 6 or 12 months. Three participants with knee osteoarthritis in the sham intervention group and two participants with hand osteoarthritis in the low-dose radiation therapy group had serious adverse effects, none of which were considered to be related to the intervention.
Interpretation: We did not find evidence of a delayed effect of low-dose radiation therapy for patients with knee and hand osteoarthritis. Our placebo-controlled results suggest that the large effects of low-dose radiation therapy reported in clinical practice and observational studies can probably be explained by a regression to the mean effect and response to placebo.
Funding: Dutch Arthritis Foundation and Stichting Landelijk Katholiek Reumacentrum, Netherlands.
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