ABSTRACT
OBJECTIVE: This observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis. METHODS: We investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (≤30â days), and (3) death after SI without known sepsis (≤90â days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously. RESULTS: Sepsis within 30â days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90â days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk. CONCLUSIONS: These results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.
Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Biological Products/adverse effects , Sepsis/mortality , Adult , Age Factors , Aged , Cohort Studies , Female , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Male , Middle Aged , Risk Factors , Sepsis/chemically inducedABSTRACT
OBJECTIVES: To demonstrate the non-inferiority of celecoxib compared with diclofenac in subjects with ankylosing spondylitis (AS). METHODS: The basis of the present work was a 12-week randomised, double-blind, controlled study in active AS subjects with three treatment arms: celecoxib 200 mg once a day, celecoxib 200 mg twice a day, and diclofenac SR 75 mg twice a day. The primary efficacy endpoint was the change from baseline in global pain intensity on a visual analogue scale (VAS) at week 12. Secondary endpoints covered changes in disease activity, functional and mobility capacities, and adverse events. RESULTS: A total of 458 subjects were randomly assigned to either celecoxib 200 mg once a day (n = 153), celecoxib 200 mg twice a day (n = 150), or diclofenac (n = 155). Least square (LS) mean changes from baseline at week 12 on a pain VAS were clinically relevant in all treatment groups (celecoxib 200 mg once a day: -29.1 mm; celecoxib 200 mg twice a day:-31.7 mm; diclofenac:-32.7 mm) and non-inferior when compared to diclofenac. Ankylosing Spondylitis Assessment Study group 20% (ASAS 20) response and mean improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores at week 12 were numerically better on celecoxib 200 mg twice a day (59.7% and-1.32 points) and on diclofenac (60.2% and-1.48 points) than on celecoxib 200 mg once a day (46.0% and-0.99 points). The incidence of gastrointestinal adverse events was significantly higher on diclofenac (28.4%) than on celecoxib 200 mg once a day (15.0%) or 200 mg twice a day (16.7%). CONCLUSIONS: The efficacy of celecoxib 200 mg once a day and 200 mg twice a day was comparable to that of diclofenac 75 mg twice a day with respect to pain reduction. Celecoxib 200 mg twice a day and diclofenac reduced some parameters associated with inflammation more effectively than celecoxib 200 mg once a day. Treatment was well tolerated, with celecoxib (either dose) exhibiting less frequent gastrointestinal adverse events than diclofenac.
Subject(s)
Diclofenac/therapeutic use , Pyrazoles/administration & dosage , Spondylitis, Ankylosing/drug therapy , Sulfonamides/administration & dosage , Adolescent , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Celecoxib , Cyclooxygenase Inhibitors/administration & dosage , Cyclooxygenase Inhibitors/adverse effects , Cyclooxygenase Inhibitors/therapeutic use , Diclofenac/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Gastrointestinal Diseases/chemically induced , Humans , Male , Middle Aged , Pain Measurement , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Severity of Illness Index , Sulfonamides/adverse effects , Sulfonamides/therapeutic use , Treatment OutcomeSubject(s)
Antibodies, Antinuclear/analysis , Autoantigens/immunology , Autoimmune Diseases/diagnosis , RNA, Small Cytoplasmic , Ribonucleoproteins , Adolescent , Adult , Aged , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Child , Child, Preschool , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Prospective Studies , Retrospective StudiesABSTRACT
The major caudal nerves of the rat provide an excellent model for longitudinal evaluation of nerve repair following a crush lesion. The surgical procedure and the method for testing sensory recovery are described in detail. Using this technique a clear, positive effect of ORG.2766 (an ACTH (4-9) analog) on the regeneration of sensory nerves could be shown. Results support the suggestion that ORG.2766 enhances the initial sprouting response, rather than exerting an effect on the growth rate of newly developed sprouts.
