HLA-DRB1 typing in rheumatoid arthritis: predicting response to specific treatments.

OBJECTIVE: To determine the predictive value of shared epitope alleles for response to treatment in patients with rheumatoid arthritis. METHODS: Patients from our previously published triple DMARD study were tested for the presence of shared epitope alleles (DRB1 *0401, 0404/0408, 0405, 0101, 1001, and 1402). Patients who were shared epitope positive were then compared with those who were negative to see if there was a differential effect on therapeutic response. RESULTS: Shared epitope positive patients were much more likely to achieve a 50% response if treated with methotrexate-sulphasalazine-hydroxychloroquine compared with methotrexate alone (94% responders versus 32%, p < 0.0001). In contrast shared epitope negative patients did equally well regardless of treatment (88% responders for methotrexate-sulphasalazine-hydroxychloroquine versus 83% for methotrexate). Additionally, a trend toward an inverse relation of the gene dose was seen for response to methotrexate treatment (p = 0.05). CONCLUSIONS: These data suggest that determining shared epitope status may provide clinical information useful in selecting among treatment options.

Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease. METHODS: The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of <1 year duration into a 6-month study of minocycline (100 mg twice daily) versus placebo. All patients were rheumatoid factor positive. The primary end point of the study was successful completion of 6 months of treatment with no drug toxicity while maintaining 50% improvement in composite symptoms of arthritis. RESULTS: Eighteen of the 46 patients who were enrolled met 50% improvement criteria at 3 months, and maintained at least a 50% improvement for 6 months with no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001). CONCLUSION: In patients with early seropositive RA, therapy with minocycline is superior to placebo.

Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications.

BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrexate.

Rheumatoid arthritis (RA) has a profound effect on patients, producing significant morbidity and in some cases mortality. Because of this, most rheumatologists are moving to disease modifying antirheumatic drug (DMARD) therapy earlier in the course of RA. Methotrexate (MTX) has become the initial DMARD of choice for most rheumatologists. Unfortunately, treatment of RA with a single DMARD, including MTX, often results in a suboptimal response. Therefore, most rheumatologists are now using combinations of DMARD to treat patients with RA who have had incomplete responses to single DMARD therapy. The Rheumatoid Arthritis Investigational Network (RAIN) reported the results of a double blind, controlled comparison of triple drug therapy (MTX-sulfasalazine-hydroxychloroquine) against MTX alone, and against the combination of hydroxychloroquine and sulfasalazine. Twenty-eight patients who had suboptimal responses to MTX or the combination of sulfasalazine and hydroxychloroquine were then treated with triple therapy in an open label study. Fourteen had previously failed MTX therapy, and 14 had previously failed combination therapy with sulfasalazine and hydroxychloroquine. Both groups had statistically significant improvements in sedimentation rates, morning stiffness, swollen joint scores, tender joint scores, patient global status assessment, and physician global status assessment. Statistical significance was reached for all these variables for patients in both groups, but improvement was greater for the patients in the sulfasalazine-hydroxychloroquine group. Patients with RA who have had suboptimal responses to MTX, or to the combination of sulfasalazine-hydroxychloroquine, show both statistical and clinically significant improvement in multiple clinical variables when treated with the combination of MTX 17.5 mg/week, sulfasalazine 500 mg bid, and hydroxychloroquine 200 mg bid.

Cortical blindness: the changing incidence and shifting etiology.

The incidence and etiology of cortical blindness--a disorder that usually occurs after cerebrovascular accidents, cardiorespiratory arrest, severe head trauma, or bacterial meningitis--may be changing with the development of effective means of cardiopulmonary resuscitation, as three cases discussed here show.