Rheumatoid Arthritis: McKenna F

McKenna F. · Trafford General Hospital, Davyhulme, Manchester, UK. · Scand J Rheumatol Suppl. · Pubmed #10422543 No free full text.

Abstract: Several currently available nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their relative selectivity in inhibiting the two cyclooxygenase (COX) isozymes, COX-1 and COX-2. Arguments have been made that more selective inhibitors of COX-2 will be safer than less selective ones. Rankings of the COX-2/COX-1 inhibition ratios of various NSAIDs as they relate to the agents' toxicities have been used as evidence that COX-2 selectivity is an important factor in the upper gastrointestinal (GI) safety of some NSAIDs. Unfortunately, none of these claims has been supported by endoscopy studies in treated patients. Since all NSAIDs inhibit COX-1, they all cause upper GI mucosal damage. What is needed are specific COX-2 inhibitors that do not inhibit COX-1. Such agents are currently under development. Ongoing clinical trials will determine the potential role for specific COX-2 inhibitors in the treatment of arthritis and pain. If specific COX-2 inhibitors are shown to be both safe and effective, the treatment of rheumatic diseases will be revolutionized.

Bombardieri S, Ruiz AA, Fardellone P, Geusens P, McKenna F, Unnebrink K, Oezer U, Kary S, Kupper H, Burmester GR, Anonymous00347. · Department of Internal Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy. · Rheumatology (Oxford). · Pubmed #17504821 links to  free full text

Abstract: OBJECTIVE: To evaluate the effectiveness and safety of adalimumab in patients with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor (TNF) antagonists for any reason in clinical practice. METHODS: ReAct (Research in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled adults with active RA who had previously been treated with traditional disease-modifying anti-rheumatic drugs or biological response modifiers. Patients self-administered adalimumab 40 mg subcutaneously every other week for 12 weeks and were allowed to enter an optional long-term extension phase. Measures of adalimumab effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, Disease Activity Score 28 (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ DI). RESULTS: Of 6610 patients, 899 had a history of etanercept and/or infliximab therapy; these patients experienced substantial clinical benefit from adalimumab treatment. At week 12, 60% of patients had an ACR20 and 33% had an ACR50 response; 76% had a moderate and 23% had a good EULAR response. In addition, 12% achieved a DAS28 < 2.6, indicating clinical remission, and 13% achieved a HAQ DI score <0.5. The allergic adverse event rate, regardless of relationship to adalimumab, was 6.5/100-patient-years (PYs) in previously TNF-antagonist-exposed patients and 4.3/100-PYs in TNF-antagonist-naive patients. A multiple regression analysis indicated no statistically significantly increased risk of serious infections in patients who received prior TNF antagonists compared with TNF-antagonist-naive patients. CONCLUSION: In typical clinical practice, adalimumab was effective and well-tolerated in patients with RA previously treated with etanercept and/or infliximab.

McKenna F, Arguelles L, Burke T, Lefkowith J, Geis GS. · Rheumatic Diseases Unit, Trafford General Hospital, Manchester, UK. · Clin Exp Rheumatol. · Pubmed #11892706 No free full text.

Abstract: OBJECTIVE: To compare the upper gastrointestinal (UGI) tolerability of celecoxib (a cyclooxygenase-2 specific inhibitor) and diclofenac using data from three randomised, double-blind clinical trials in osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: Patients in two OA studies received either celecoxib 100 mg BID (n = 545), diclofenac 50 mg BID or TID (n = 540), or placebo (n = 200) for 6 weeks. In the RA study, patients received celecoxib 200 mg BID (n = 326) or diclofenac 75 mg BID (n = 329) for 24 weeks. The cumulative incidence of abdominal pain, dyspepsia, nausea or any of these events (UGI tolerability composite endpoint) after the first 6 weeks was estimated using time-to-event analysis. RESULTS: In the pooled OA trials, the cumulative incidence of the composite endpoint was significantly higher with diclofenac (17.6%; 95% CI: 14.4-20.9%) than celecoxib (11.1%; 95% CI: 8.4-13.8%; p = 0.002) and comparable with placebo (13.3%; 95% CI: 8.1-18.4%; p = 0.157). In the PA trial, the cumulative incidence of the UGI tolerability composite endpoint was also significantly higher with diclofenac (20.7%; 95% CI: 16.3-25.1%) than celecoxib (15.9%; 95% CI: 11.9-20.0%; p = 0.013). Celecoxib was also better tolerated than diclofenac in this trial in terms of the cumulative incidences of abdominal pain (p = 0.031) and dyspepsia (p = 0.062). The results of the UGI tolerability composite endpoint analysis were confirmed using the Cox proportional hazards model to controlfor other predictors of UGI adverse events. CONCLUSION: The UGI tolerability of therapeutic dosages of celecoxib was significantly better than diclofenac in patients with RA or OA.

Chinoy H, McKenna F. · No affiliation provided · Rheumatology (Oxford). · Pubmed #12011387 links to  free full text

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