Rheumatoid Arthritis: Recker DP

Goldstein JL, Kivitz AJ, Verburg KM, Recker DP, Palmer RC, Kent JD. · University of Illinois at Chicago, Chicago, IL 60612, USA. · Aliment Pharmacol Ther. · Pubmed #12848634 links to  free full text

Abstract: BACKGROUND: In long-term outcomes studies, cyclooxygenase COX-2 specific inhibitors spare COX-1 at supratherapeutic doses and therefore demonstrate improved gastrointestinal safety over nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs). However, in clinical practice, anti-inflammatory drugs are often used for short-term treatment of pain. AIM: To compare the short-term upper gastrointestinal mucosal effects of naproxen with the new COX-2 specific inhibitor, valdecoxib, or placebo, in elderly subjects. METHODS: In this multicentre, double-blind, randomized, study, elderly subjects (65-76 years old), with a normal baseline esophagogastroduodenoscopy (EGD), received oral valdecoxib (a supratherapeutic 40 mg b.d. dosage, n = 62), naproxen (500 mg b.d., n = 62), or placebo (n = 62) for 6.5 days. Upper gastrointestinal mucosal injury was evaluated post-treatment by EGD (day 7). RESULTS: Subjects receiving naproxen (11/60, 18%) had significantly more gastroduodenal ulcers post-treatment than those receiving placebo (2/61, 3%; P < 0.01) or valdecoxib (0/60, 0%; P < 0.001). A similar significant finding was observed for gastric ulcer rates. All treatments had similar adverse event rates and clinical laboratory findings. CONCLUSIONS: Valdecoxib, even at supratherapeutic doses, was associated with an ulcer rate significantly lower than naproxen but similar to placebo in healthy elderly subjects, despite the short duration of therapy (6.5 days). Naproxen and valdecoxib were as well tolerated as placebo.

Pavelka K, Recker DP, Verburg KM. · Institute of Rheumatology, Prague, Czech Republic. · Rheumatology (Oxford). · Pubmed #12810937 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy and upper gastrointestinal (GI) safety of valdecoxib 20 and 40 mg daily with those of diclofenac 75 mg slow release (SR) twice daily in treating rheumatoid arthritis (RA). METHODS: Seven hundred and twenty-two patients with adult-onset RA were enrolled into this 26-week, randomized, multicentre, double-blind, parallel-group study (246 in the valdecoxib 20 mg daily arm, 237 in the valdecoxib 40 mg daily arm and 239 in the diclofenac 75 mg SR daily arm). Acetylsalicylic acid use (< or =325 mg per day) was similar across all groups: 5.4% in the diclofenac group, 5.7% in the valdecoxib 20 mg group and 5.9% in the valdecoxib 40 mg group. Efficacy was measured by the Patient's Assessment of Arthritis Pain [visual analogue scale (VAS)] and the modified Health Assessment Questionnaire (mHAQ) at baseline and at weeks 2, 6, 8, 12, 18 and 26 of treatment, or at early termination. Upper GI safety was evaluated by endoscopy at the end of treatment, which took place no more than 2 days after the last dose of study medication or at early termination. RESULTS: Valdecoxib 20 and 40 mg daily were comparable to diclofenac 75 mg SR twice daily in treating the signs and symptoms of RA. No significant differences were observed between treatment groups with respect to mean changes from baseline in the Patient's Assessment of Arthritis Pain (VAS) or mHAQ. The incidence of gastroduodenal ulcers in patients receiving valdecoxib 20 mg daily (6%) and valdecoxib 40 mg daily (4%) was significantly lower (P < 0.001) than in patients receiving diclofenac 75 mg SR twice daily (16%). Valdecoxib 20 mg daily was also associated with significantly improved GI tolerability (P = 0.035) compared with diclofenac. CONCLUSIONS: Single daily doses of valdecoxib 20 and 40 mg provided efficacy comparable to that of diclofenac, with a superior upper GI safety profile in the long-term treatment of RA patients.

Bensen W, Weaver A, Espinoza L, Zhao WW, Riley W, Paperiello B, Recker DP. · St Joseph's Hospital and McMaster University, Hamilton, ON, Canada. · Rheumatology (Oxford). · Pubmed #12209034 links to  free full text

Abstract: OBJECTIVE: To compare the efficacy of the COX-2 specific inhibitor valdecoxib with the conventional NSAID naproxen and placebo in treating rheumatoid arthritis (RA). METHODS: This multi-centre, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of valdecoxib 10 mg (n=209), 20 mg (n=212) or 40 mg once daily (q.d.) (n=221) with naproxen 500 mg b.i.d. (n=226) or placebo (n=222), in treating the signs and symptoms of RA. Efficacy was assessed by the number of patients responding to treatment according to the American College of Rheumatology-Responder Index (ACR-20). RESULTS: ACR-20 response was recorded for all randomized patients who received a single dose of study medication (above). Valdecoxib, at all administered doses, produced significant improvements in the ACR-20 Responder Index at weeks 2, 6 and 12 compared with placebo (P<or=0.01). Valdecoxib and naproxen did not differ in terms of ACR-20 response rate and the three doses of valdecoxib were similar to one another. All three doses of valdecoxib were well tolerated. CONCLUSIONS: Single daily doses of valdecoxib 10, 20 and 40 mg demonstrated efficacy that was superior to placebo and similar to naproxen in treating the signs and symptoms of RA. All three doses provided similar levels of efficacy.