A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS OF PHARMACOLOGICAL THERAPY IN OSTEOARTHRITIS OF THE KNEE, WITH AN EMPHASIS ON TRIAL METHODOLOGY

We systematically reviewed randomized controlled trials (RCTs) of phar macological therapy in knee osteoarthritis (OA), published between 196 6 and August 1994. RCTs were identified by MEDLINE, supplemented by a manual search of reference lists. Qualitative assessment of RCTs was p erformed using Gotzsche's method; design and analysis features were ra ted on a scale of 0 (worst) to 8 (best). Heller et al's method was use d to compare efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) in comparative trials. A total of 80 RCTs were analyzed (45 involved N SAIDs, 3 analgesics, 5 intraarticular [IA] steroids, 9 biological agen ts, including IA hyaluronic acid, and 18 mixed modalities, including t opical capsaicin). The median design and analysis scores for all 80 RC Ts were 2 and 5, respectively. NSAIDs were superior to placebo in all short-term trials, but in the 32 comparative NSAID trials, only five ( 16%) found significant differences in efficacy. Heller et al's method identified differences in 14 NSAID comparisons; etodolac (600 mg/day) was superior in five of its nine comparisons. Indomethacin and aspirin were the most toxic NSAIDs. IA steroids were superior to placebo in s hort-term efficacy (<1 month). Biological agents were superior to plac ebo and generally well tolerated over a mean follow-up of 48 weeks. Ac etaminophen was superior to placebo and was comparably efficacious to low-dose naproxen and ibuprofen (<2,400 mg/day). The data support the use of acetaminophen, topical capsaicin, IA steroids, IA hyaluronic ac id, and NSAIDs in the treatment of patients with knee OA. (C) 1997 by W.B. Saunders Company.