Nonsteroidal antiinflammatory drug withdrawal in patients with stable rheumatoid arthritis.

OBJECTIVE: To evaluate the effect of nonsteroidal antiinflammatory drug (NSAID) withdrawal on blood pressure (BP), 44-joint Disease Activity Score (DAS44), and functional assessments in patients with stable rheumatoid arthritis (RA). METHODS: NSAID was withdrawn from 30 patients with stable RA (DAS44 ≤ 2.8). Other prescribed medication continued. Clinical and laboratory measures were taken at baseline, 6 weeks, and 12 weeks. RESULTS: No participants required NSAID reintroduction during the study period. Significant improvement in systolic BP was noted: maximal median reduction was 7 mm Hg (baseline to 12 weeks). There was no significant deterioration in DAS44 or function. Eleven participants required additional intervention. CONCLUSION: NSAID withdrawal resulted in improvement in BP without loss of disease control.

Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study.

BACKGROUND: Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. AIM: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. METHODS: A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. RESULTS: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. CONCLUSIONS: In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.

The frequency and distribution of minocycline induced hyperpigmentation in a rheumatoid arthritis population.

OBJECTIVE: Minocycline is particularly useful in patients with rheumatoid arthritis (RA) with previous major sepsis, where anti-tumor necrosis factor is relatively contraindicated. Pigmentation is a documented side effect, but predisposing factors in an RA population have not been established. We investigated minocycline induced pigmentation in a population with RA to determine whether skin type and eye color influence predisposition to this side effect. METHODS: Patients with RA attending a rheumatology unit who had received minocycline were contacted by telephone and some were also interviewed in the clinic. Those receiving therapy for more than 3 months were assessed. Hair color, eye color, tendency to burn in the sun, and dose and duration of therapy were documented. The frequency, type, and distribution of pigmentation were established. RESULTS: Of 37 patients identified, 10 were excluded because the duration of therapy was less than 3 months. Of the remaining 27 patients, 85% were female, with median age 64 years (range 44-88) and median disease duration 23.5 years (range 4-51). Eleven patients (41%) developed pigmentation after a median of 12 months. Four of the 11 stopped their minocycline due to pigmentation. Hair color, eye color, and tendency to burn in the sun did not predict patients who developed pigmentation. CONCLUSION: Pigmentation is a common side effect in patients receiving minocycline therapy for more than 3 months. Most patients do not stop therapy due to pigmentation. Those who stop are more likely to be female, less than 70 years of age, and have facial pigmentation.

Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.

BACKGROUND: Rheumatoid arthritis is characterised by inflammatory synovitis, articular destruction, and accelerated atherogenesis. HMG-CoA (3-hydroxy-3-methylglutarylcoenzyme A) reductase inhibitors (statins) mediate clinically significant vascular risk reduction in patients without inflammatory disease and might have immunomodulatory function. We postulated that statins might reduce inflammatory factors in rheumatoid arthritis and modify surrogates for vascular risk. METHODS: 116 patients with rheumatoid arthritis were randomised in a double-blind placebo-controlled trial to receive 40 mg atorvastatin or placebo as an adjunct to existing disease-modifying antirheumatic drug therapy. Patients were followed up over 6 months and disease activity variables and circulating vascular risk factors were measured. Coprimary outcomes were change in disease activity score (DAS28) and proportion meeting EULAR (European League Against Rheumatism) response criteria. Analysis was by intention to treat. FINDINGS: At 6 months, DAS28 improved significantly on atorvastatin (-0.5, 95% CI -0.75 to -0.25) compared with placebo (0.03, -0.23 to 0.28; difference between groups -0.52, 95% CI -0.87 to -0.17, p=0.004). DAS28 EULAR response was achieved in 18 of 58 (31%) patients allocated atorvastatin compared with six of 58 (10%) allocated placebo (odds ratio 3.9, 95% CI 1.42-10.72, p=0.006). C-reactive protein and erythrocyte sedimentation rate declined by 50% and 28%, respectively, relative to placebo (p<0.0001, p=0.005, respectively). Swollen joint count also fell (-2.69 vs -0.53; mean difference -2.16, 95% CI -3.67 to -0.64, p=0.0058). Adverse events occurred with similar frequency in patients allocated atorvastatin and placebo. INTERPRETATION: These data show that statins can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation.

A longitudinal study of lung function in nonsmoking patients with rheumatoid arthritis.

STUDY OBJECTIVE: s: Patients with rheumatoid arthritis (RA) have a high prevalence of pulmonary function test (PFT) abnormality, but the long-term significance of this is unknown. We performed a longitudinal study of pulmonary function in asymptomatic, nonsmoking patients with active RA requiring disease-modifying drugs. We looked for temporal change in lung function and characteristics that would predict subsequent development of PFT abnormality or respiratory symptoms. METHODS: In 1990, 52 patients (44 women; age range, 29 to 78 years; median, 56 years) underwent clinical assessment (drug history, RA severity, immunologic, and inflammatory markers) and PFTs (spirometry, body plethysmography, gas transfer). PFT results were expressed as standardized residuals (SRs). Thirty-eight patients were reassessed in 2000. A self-administered questionnaire was used to identify respiratory symptoms. RESULTS: The prevalence of pulmonary function abnormality was higher than expected compared with a reference population, but there was no significant increase in number over 10 years (8.7% in 1990 and 8.8% in 2000). When assessed by group means and compared with reference values, reduced diffusing capacity of the lung for carbon monoxide (DLCO) and increased ratio of residual volume (RV) to total lung capacity (TLC) [RV/TLC] were the only abnormalities to develop over the study period (mean DLCO in 2000, - 0.47 SR; 95% confidence interval [CI], - 0.91 to - 0.01; RV/TLC, 0.49 SR; 95% CI, 0.13 to 0.84). However, rates of change of pulmonary function variables were not significantly different from zero. Logistic regression did not identify any meaningful relationship between disease characteristics and PFT abnormality. CONCLUSIONS: Asymptomatic patients with RA have a higher prevalence of PFT abnormality than expected, but these do not increase in number over time. We did not identify any patient or disease-specific characteristic that could predict the development of respiratory disease in patients with RA. Analysis using percentage of predicted values, rather than SRs, is misleading as it exaggerates the extent of abnormality present. Abnormal lung function is a common and probably benign finding in nonsmoking, asymptomatic patients with RA.