Bernard R. Rubin

Association of baseline disease and patient characteristics with response to etoricoxib and indomethacin for acute gout.

ABSTRACT Background and objective: Disease history and clinical features can influence treatment response in patients with acute gout. The purpose of this pooled subgroup analysis was to assess the association of baseline disease and patient characteristics with response to treatment in acute gout using data from two identical studies. Methods: Patients ≥ 18 years of age with onset of acute gout within 48 h associated with moderate, severe, or extreme pain involving less than four joints were eligible for inclusion in the primary studies, and were randomized to etoricoxib 120 mg once daily (N = 178) or indomethacin 50 mg three times daily (N = 161). The primary and secondary efficacy endpoints were analyzed using an analysis of covariance model to detect potential differential treatment responses across several subgroups: joint involvement (mono-articular vs. oligo-articular), baseline pain severity (moderate vs. severe), concomitant allopurinol and/or colchicine use (users vs. nonusers), age (< 45, 45–55, and > 55 years), gender, and race (white or other). Results: Overall, etoricoxib and indomethacin demonstrated comparable efficacy across all subgroups. Compared with patients with oligo-articular disease, those with mono-articular disease had significantly greater improvements in patient assessment of pain, patient global assessment of response to therapy (PGART), investigator global assessment of response to therapy (IGART), and study joint tenderness ( p < 0.001 for all). Greater improvements were seen in patient assessment of pain ( p < 0.001) and study joint tenderness ( p < 0.05) for severe/extreme baseline pain compared with moderate baseline pain. Concomitant use of colchicine and/or allopurinol was associated with significantly worse IGART ( p < 0.05). Conclusions: This pooled subgroup analysis demonstrated significantly greater response of acute gout to either etoricoxib or indomethacin among those with monoarticular disease, severe/extreme baseline pain, and non-use of colchicine and/or allopurinol. These results should be interpreted in the context of a pooled subgroup analysis with a limited sample size, and with the understanding that associations identified in such analyses do not define causation. Despite limitations, the results provide insights into the types of patients more likely to respond better to anti-inflammatory medication, and reiterate the importance of earlier effective control of the disease.

Rofecoxib 12.5 mg, rofecoxib 25 mg, and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies.

ABSTRACT Objective: To compare the efficacy of rofecoxib and celecoxib for the treatment of knee or hip OA over 6 weeks. Methods: Two similarly designed, multicenter, randomized, double-blind, placebo-controlled studies. Patients were randomly assigned 3:3:3:1 in Study 1 to once daily (QD) rofecoxib 12.5 mg (N = 456), rofecoxib 25 mg (N = 459), celecoxib 200 mg (N = 456), or placebo (N = 150) and 3:3:1 in Study 2 to QD rofecoxib 25 mg (N = 471), celecoxib 200 mg (N = 460), or placebo (N = 151). There was no rofecoxib 12.5 mg arm in Study 2. The primary outcome measure of both studies was pain at night over 6 weeks for rofecoxib 25 mg vs. celecoxib 200 mg. Efficacy comparisons with rofecoxib 12.5 mg in Study 1 were included as pre-specified study objectives but not as pre-specified study hypotheses. Secondary endpoints included Patient Global Assessment of Response to Therapy (PGART) over 6 weeks and over 1 week. Safety was evaluated through the assessment of spontaneously reported adverse experiences (AEs), evaluation of vital signs, and laboratory data reported by investigators and patients. Results: For the primary endpoint, reduction in pain at night over 6 weeks in Study 1 was not significantly different between active treatments; in Study 2 rofecoxib 25 mg significantly ( p = 0.023) reduced pain at night compared with celecoxib 200 mg over 6 weeks. For the secondary endpoints, in both studies, significantly ( p < 0.05) more patients treated with rofecoxib 25 mg than celecoxib 200 mg had a good or excellent PGART over 6 weeks, and over the first week ( p < 0.01). In both studies, there were no significant differences between active medications in the incidence of reported overall, serious, or drug-related AEs. The reported AE rates with the active treatments were generally similar to those with placebo in the two studies. Conclusions: Rofecoxib 25 mg was significantly better than celecoxib 200 mg in relieving night pain at 6 weeks in one study; this was not confirmed in the accompanying study.

Poly(ADP-ribose) Synthesis in Lymphocytes of Systemic Lupus Erythematosus Patients

Several studies have implicated altered poly(ADP-ribose) metabolism in the disease systemic lupus erythematosus (SLE). For example, circulating antibodies to poly(ADP-ribose) (1, 2) and poly(ADP-ribose) polymerase (3) have been reported in patients with SLE. In addition, Sibley et al. (4) have reported a 70 percent decrease in the accumulation of ADP-ribose polymers of peripheral blood lymphocytes of patients with SLE. We have confirmed this finding and report here studies on the mechanism of this defective metabolism.