Background:S-adenosylmethionine (SAMe) has antiinflammatory and analgesie effects and has been
reported to ameliorate the pain and dysfunction of osteoarthritis (OA). The metabolism
of SAMe can be affected by geographic or ethnic factors. However, its efficacy and
tolerability versus NSAIDs have not been reported in an Asian population.
Objective: This study compared the efficacy and tolerability of SAMe 1200 mg/d and nabumetone
1000 mg/d in Korean patients with knee OA.
Methods: This study was an 8-week, multicenter, randomized, double-blind, double-dummy, Phase
IV clinical trial. Eligible patients were aged >18 years and had knee OA according
to the clinical and radiologic criteria of the American College of Rheumatology, with
a symptom duration of ≥3 months and with a baseline pain rating of >40 mm on a visual
analog scale (VAS) or a pain rating on the VAS that was increased by >10 mm or 20%
during the washout period compared with the screening visit. After a washout period
of 2 weeks, patients with OA were randomly assigned to receive SAMe 1200 mg/d (400
mg TID) or nabumetone 1000 mg once a day in the evening for 8 weeks. The primary end
point was the patient's assessment of pain intensity using a VAS at week 8, and the
secondary end points were functional class, patient's global assessment of disease
status, physician's global assessment of response to therapy, and the Western Ontario
and McMaster Universities (WOMAC) index. Adverse events were assessed based on spontaneous
reports by patients during interviews and by laboratory tests.
Results: One hundred thirty-four patients, all Asians, were randomly allocated to 1 of 2 treatment
groups: 67 patients (56 women, 11 men; mean [SD] age, 63.9 [8.2] years) received SAMe
400 mg TID, and 67 patients (60 women, 7 men; mean age, 62.1 [8.4] years) received
nabumetone 1000 mg once daily for 8 weeks. An analysis of changes in pain intensity
between weeks 0 and 8 found that both SAMe and nabumetone effectively reduced pain
intensity from baseline in each group (mean [SD] change: SAMe, −13.0 [20.8] mm, P < 0.001; nabumetone, −15.7 [20.9] mm, P < 0.001), and the degree of decrease in pain intensity was not significantly different
between groups. Secondary end points showed significant improvements from baseline
to 8 weeks in both groups. The patient's global assessment of disease status, physician's
global assessment of response to therapy, and WOMAC index scores were not significantly
different between the groups. Use of acetaminophen as rescue medication did not differ
significantly between the groups during weeks 0 to 4 (SAMe, 88.5% [54/61]; nabumetone,
81.3% [52/64]) or weeks 4 to 8 (SAMe, 79.5% [35/44]; nabumetone, 68.5% [37/54]). No
significant differences were observed between the treatments in the proportions of
patients with all adverse events (SAMe, 35.8% [24/67]; nabumetone, 31.3% [21/67]),
drugrelated clinical or laboratory-determined adverse events (SAMe, 22.4% [15/67];
nabumetone, 25.4% [17/67]), or discontinuations due to any adverse events (SAMe, 13.4%
[9/67]; nabumetone, 10.4% [7/67]).
Conclusion: This study found no significant differences in pain relief or tolerability between
treatment with SAMe or nabumetone over 8 weeks in Korean patients with knee OA.