[Interstitial lung disease in connective tissue diseases]. / Pneumopathies interstitielles liées aux connectivites.

Interstitial lung disease represents a major clinical aspect of the four major connective tissue diseases: rheumatoid arthritis, scleroderma, polymyositis/dermatomyositis and systemic lupus erythematosus (SLE). Early recognition in the course of the disease is essential, as interstitial lung disease will often determine the vital prognosis of these patients. Treatment is most frequently based on experts' opinion, because there are only few randomized controlled trials in this field.

Rituximab in systemic lupus erythematosus: an updated systematic review and meta-analysis.

The wide spectrum of clinical manifestations and high relapse rate represent a therapeutic challenge in systemic lupus erythematosus (SLE). Observational studies suggested efficacy of rituximab (RTX), a B-cell-targeting antibody, to control the activity of SLE. Two randomized trials controlled by placebo did not prove the superiority of RTX when used in addition to conventional treatment in nonrenal (EXPLORER) and renal (LUNAR) lupus. A systematic review of studies exploring the efficacy of RTX in SLE patients was conducted. The pooled percentages of response were assessed. Thirty studies with 1243 patients were analyzed. In studies using the British Isles Lupus Assessment Group (BILAG), the complete response (CR) rate was 46.7% (95% CI 36.8%-56.8%) and the partial response (PR) was 37.9% (95% CI 30.6%-45.8%). With the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the CR was 56.6% (95% CI 32.4%-78.1%) and the PR was 30.9% (95% CI 8.9%-46%). In renal lupus the CR was 36.1% (95% CI 25.2%-48.6%); PR was 37.4% (95% CI 28.5%-47.3%). In EXPLORER, CR was 12.4% and PR was 17.2%; in LUNAR CR was 26.4% and PR was 30.6%, in both cases not different from controls. Assessment and standardization of SLE response to treatment remain a challenge. The discrepancy in the perceived efficacy of RTX between controlled and observational studies reflects the heterogeneity of lupus and stringency in criteria of response. Further randomized trials focusing on selected SLE manifestations and using composite response indices are warranted.

The oral anticoagulant saga: past, present, and future.

Oral anticoagulation originated with the discovery of the harmful agent causing "sweet clover disease" in cattle in North America in the 1920s. The causative agent dicoumarol was isolated in Link's laboratory in 1940. A range of related compounds was then synthesized, the most popular of which proved to be warfarin. Oral anticoagulant administration posed problems of individual variation in response to these drugs and the need for regular laboratory monitoring by prothrombin time (PT). Monitoring problems arose from the introduction in the 1950s of some poorly responsive commercial tissue extracts for use as tissue extract thromboplastin reagent in the PT. More oral anticoagulant drug was then needed to prolong the test to the required therapeutic targets, with a resultant increase in bleeding. It was not until 1983 that the problem was resolved and it was shown that the less intense UK-type regimen was just as effective as the higher North American type dosage in the prevention of venous thrombosis but caused much less bleeding. This study led to the widespread adoption of the "low-dose warfarin" regimen that, combined with the World Health Organization PT standardization scheme using the international normalized ratio (INR), has led to improved effectiveness and safety of oral anticoagulation. This has permitted increased administration of warfarin in a widening spectrum of clinical disorders. The last remaining problem is the limited success of doctors in achieving the therapeutic INR targets, which may be improved by computer-assisted dosage.

Therapeutic quality control leading to further clinical assessment of oral anticoagulation.

Oral anticoagulant therapy has been practiced for 40 years but we still do not have definitive evidence of its value. Early clinical trials are now discounted due to the varying quality and lack of standardisation of the thromboplastins then available. There was also no statistical evidence that therapy was adequately maintained. We now have sensitive and reliable thromboplastins and there is an international standardisation of calibration and of reporting prothrombin time. With therapeutic quality control of oral anticoagulation and the so treated patients clinical assessed, we might hope that definitive evidence of the value of this therapy would result.

Therapeutic control of anticoagulant treatment.

Control of anticoagulant treatment was studied in 250 patients. One hundred and fifty patients receiving long-term anticoagulant treatment (group 1) were studied for 52 weeks and the remaining 100 (group 2) for 12 weeks after discharge from hospital. The desired British correlated ratio range was 2.5-3.3, and a range of 2.3-3.5 was classified as satisfactory. In group 1 a satisfactory ratio was obtained for 70% of the study period and 120 of the 150 patients were maintained within this range for over 60% of the time. In group 2 only half of the patients were maintained within the satisfactory range and for 50% of the study period or less. The time and effort expended in therapeutic control were more than most clinics could afford, and the results for group 2 were disappointing. The standard of long-term anticoagulant treatment should be improved by continuous review of control and by "therapeutic quality control."