Effect of Low-dose Oral Prednisolone on Symptoms and Systemic Inflammation in Older Adults with Moderate to Severe Knee Osteoarthritis: A Randomized Placebo-controlled Trial

Abstract

To investigate the efficacy of 6 weeks of daily low-dose oral prednisolone in improving pain, mobility, and systemic low-grade inflammation in the short term and whether the effect would be sustained at 12 weeks in older adults with moderate to severe knee osteoarthritis (OA). A total of 125 patients with primary knee OA were randomized 1:1; 63 received 7.5 mg/day of prednisolone and 62 received placebo for 6 weeks. Outcome measures included pain reduction and improvement in function scores and systemic inflammation markers. Pain was assessed using the visual analog pain scale (0-100 mm). Secondary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index scores, patient global assessment (PGA) of the severity of knee OA, and 6-min walk distance (6MWD). Serum levels of interleukin 1 (IL-1), IL-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were measured. There was a clinically relevant reduction in the intervention group compared to the placebo group for knee pain, physical function, PGA, and 6MWD at 6 weeks. The mean difference between treatment arms (95% CI) was 10.9 (4.8-18.0), p < 0.001; 9.5 (3.7-15.4), p < 0.05; 15.7 (5.3-26.1), p < 0.001; and 86.9 (29.8-144.1), p < 0.05, respectively. Further, there was a clinically relevant reduction in the serum levels of IL-1, IL-6, TNF-α, and hsCRP at 6 weeks in the intervention group when compared to the placebo group. These differences remained significant at 12 weeks. The Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society International responder rate was 65% in the intervention group and 34% in the placebo group (p < 0.05). Low-dose oral prednisolone had both a short-term and a longer sustained effect resulting in less knee pain, better physical function, and attenuation of systemic inflammation in older patients with knee OA (ClinicalTrials.gov identifier NCT01619163).