Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial.

BACKGROUND: Alternative therapeutic options are needed for patients with systemic lupus erythematosus (SLE) not adequately controlled with or intolerant to traditional treatments. This study evaluated the efficacy of Acthar® Gel (ACTH(1-39)) for reducing active SLE severity among patients receiving underlying conventional maintenance therapies. METHODS: Ten females (mean age = 49 yrs, disease duration = 7 yrs, Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2 K] = 10) currently on maintenance self-administered ACTH(1-39) gel 1 mL (80 U/mL) for 7-15 days and were assessed weekly for 28 days. Outcome measures included Physician and Patient Global Assessments, SLEDAI-2 K, Lupus Quality of Life scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, erythrocyte sedimentation rate, and C-reactive protein. Student's t-test compared data obtained at days 7, 14, and 28 with those from baseline. RESULTS: The primary endpoint of SLEDAI-2 K improvement was reached at all observation times (p < 0.05) and statistically significant improvements were observed for most other parameters. No treatment-related serious or unexpected adverse events were observed. CONCLUSIONS: The trial results reveal that among SLE patients in need of therapeutic alternatives, ACTH(1-39) gel may provide significant disease activity reduction.

Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial.

OBJECTIVE: To compare the efficacy and safety of celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, with those of naproxen, a nonsteroidal anti-inflammatory drug (NSAID), and placebo in the treatment of osteoarthritis of the knee. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 1003 patients with symptomatic osteoarthritis of the knee were randomly assigned to receive celecoxib at doses of 50, 100, or 200 mg twice a day; naproxen, 500 mg twice a day; or placebo for 12 weeks. Patients were evaluated with standard measures of efficacy 2 to 7 days after discontinuing previous NSAID or analgesic therapy and after 2, 6, and 12 weeks of treatment with the study drug. RESULTS: Celecoxib treatment led to significant improvement in the signs and symptoms of osteoarthritis as determined by all efficacy measures. Significant pain relief occurred within 2 days of the initiation of treatment, and maximum anti-inflammatory and analgesic activity, evident within 2 weeks, was sustained throughout the 12-week study. All celecoxib doses were efficacious compared with placebo, although the 50-mg twice-daily dosage regimen was minimally effective. The higher doses of celecoxib (100 and 200 mg twice a day) were similarly efficacious, and the magnitude of improvement observed with these dosing regimens was comparable to that seen with naproxen at a dose of 500 mg twice a day. All doses of celecoxib and naproxen were well tolerated. CONCLUSION: COX-2 inhibition with celecoxib is an effective approach for the treatment of osteoarthritis, as seen by clinical improvement in signs and symptoms comparable to treatment with naproxen.

Manual and manipulation techniques for rheumatic disease.

Manipulation is practiced primarily by chiropractors and osteopaths and is one of the most commonly utilized alternative treatments for rheumatic diseases. Low back pain and neck pain are the most frequently treated disorders, but manipulation is also used to treat a broad range of rheumatic diseases. Manipulation has been shown to decrease joint pain and normalize function. The mechanisms of action, however, are not well understood. Current theories propose an imbalance of muscle activity is a source of pain that manipulation can relieve through reflexive actions. Such muscle imbalances would exacerbate rheumatic and arthritic conditions, suggesting that manipulation may be an important therapy that is appropriate for early conservative care as part of a comprehensive treatment program.

Reliability and validity of body composition measures in female athletes.

The purpose of this investigation was to determine the reliability and validity of bioelectrical impedance (BIA) and near-infrared interactance (NIR) for estimating body composition in female athletes. Dual-energy X-ray absorptiometry was used as the criterion measure for fat-free mass (FFM). Studies were performed in 132 athletes [age = 20.4 +/- 1.5 (SD) yr]. Intraclass reliabilities (repeat and single trial) were 0.987-0.997 for BIA (resistance and reactance) and 0.957-0.980 for NIR (optical densities). Validity of BIA and NIR was assessed by double cross-validation. Because correlations were high (r = 0.969-0.983) and prediction errors low, a single equation was developed by using all 132 subjects for both BIA and NIR. Also, an equation was developed for all subjects by using height and weight only. Results from dual-energy X-ray absorptiometry analysis showed FFM = 49.5 +/- 6.0 kg, which corresponded to %body fat (%BF) of 20.4 +/- 3.1%. BIA predicted FFM at 49.4 +/- 5.9 kg (r = 0.981, SEE = 1.1), and NIR prediction was 49. 5 +/- 5.8 kg (r = 0.975, SEE = 1.2). Height and weight alone predicted FFM at 49.4 +/- 5.7 kg (r = 0.961, SEE = 1.6). When converted to %BF, prediction errors were approximately 1.8% for BIA and NIR and 2.9% for height and weight. Results showed BIA and NIR to be extremely reliable and valid techniques for estimating body composition in college-age female athletes.

Methotrexate in rheumatoid arthritis: an update.

Methotrexate, a folic acid antagonist, is being employed more frequently in an attempt to control rheumatoid arthritis that has not responded adequately to conventional therapies. Systemic administration of 7.5-15 mg weekly in a pulse fashion appears to be effective without precipitating serious adverse effects. Concern over potentially serious adverse effects and lack of well-controlled clinical trials have limited its use to severe, refractory disease. Its use in the future is likely to increase in these patients because of its ease of administration and the high response rate noted in clinical studies.

Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial.

A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial.

Angiosarcoma of the liver in a rural population. Four cases diagnosed in a 29-month period.

Angiosarcoma of the liver has recently been publicized because of its association with polyvinyl chloride (PVC) polymerization workers. Four cases of this rare tumor have been observed at the Marshfield Clinic within a 29-month period. There are no factories that manufacture PVC products in the immediate area, nor were any of the victims ever involved in such manufacturing work. Thus, it is possible that other factors may be related to this cluster of the disease.

Urate spherulites in gouty synovia.

We have identified urate crystals in gouty synovial fluid in a spherulite form. Studies in vitro established these "beachball" structures as chemically identical to classic "needles" of monosodium urate monohydrate, the prime factor in gouty arthritis. Previously described in the 1890s by a German scientist, these structures have not been recognized by clinicians examining fluid from arthritic joints. We suggest an identification scheme for beach ball-like" structures in synovial fluid.

Reversal of neutropenia with methotrexate treatment in patients with Felty's syndrome. Correlation of response with neutrophil-reactive IgG.

We evaluated the clinical and hematologic response to methotrexate (MTX) in 4 women with Felty's syndrome (FS) who had had neutropenia for 1-3 years. Since immune complexes or antineutrophil antibodies are implicated in the pathogenesis of the neutropenia of FS, we also measured both direct and indirect levels of neutrophil-reactive IgG. All 4 patients showed a prompt and dramatic increase in neutrophil counts within 1-2 months of starting MTX therapy. In 3 patients, the symptoms of arthritis also improved; in the fourth patient, arthritis worsened. Recurring infections ceased in 3 patients. Neutrophil-reactive IgG levels, which were elevated in all patients prior to treatment, decreased toward normal while the patients were receiving MTX therapy. We conclude that MTX is effective in treating the neutropenia of FS, in part by lowering neutrophil-reactive IgG.

Roman arches, human joints, and disease: differences between convex and concave sides of joints.

The subchondral plate of bone underlying concave joint surfaces is significantly thicker, at most sites, than that under the corresponding convex mates. This morphologic difference may be related to parallel differences in loading stress and in the distribution of osteonecrosis and other joint lesions.

COX-2 specific inhibitors in the management of osteoarthritis of the knee: a placebo-controlled, randomized, double-blind study.

COX-2 specific inhibitors have demonstrated significant safety advantages and comparable efficacy in osteoarthritis (OA) compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials between COX-2 specific inhibitors have been published. In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (> or =40 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6 weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at early termination. At Week 6, celecoxib and rofecoxib treatment resulted in similar mean changes from baseline (p > 0.55) in arthritis pain visual analogue scale, patient's global assessment, and total score for WOMAC; all changes were superior to placebo (p < 0.05). In the patient's global assessment of arthritis pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients improved by > or =1 grade, compared with 50% of placebo patients (celecoxib, p = 0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the active comparators; however, celecoxib-treated patients had significantly fewer adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which suggests that celecoxib may have a better gastrointestinal tolerability profile than rofecoxib at these doses. Adverse events that prompted withdrawal occurred in fewer than 7% of patients, and the overall incidences were similar between the active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer comparable efficacy and are an effective alternative to conventional NSAIDs in the management of OA.

Plasma hydroxychloroquine concentrations and efficacy in rheumatoid arthritis.

Plasma levels of hydroxychloroquine (HCQ) and its metabolites were measured, by high performance liquid chromatography, in 37 rheumatoid arthritis patients who could be clearly distinguished as responders (n = 28) or nonresponders (n = 9) to HCQ, 400 mg/day. Efficacy in both groups was determined by the patients' erythrocyte sedimentation rates, joint counts, morning stiffness, global assessments, concurrent drug therapies, and grip strength. The response rate was 76%. Responders had a mean HCQ level of 213 ng/ml, versus 306 in nonresponders (P less than 0.05). The mean level of HCQ plus total metabolites in responders was 363 ng/ml, versus 554 in nonresponders (P less than 0.01). We conclude that monitoring plasma HCQ levels is unlikely to be helpful in individualizing effective drug dosage.

Free fatty acids in the pancreatitic arthritis syndrome.

Fat necrosis and arthritis occur in some individuals with pancreatitis. The intraarticular free fatty acid concentration was found to be markedly elevated in 2 patients with this pancreatitic arthritis syndrome. Injection of free fatty acids into rabbit knees reproduced the inflammatory synovial response including intracellular fat globules within leukocytes. Free fatty acids exceeding the available binding sites of albumin appear to mediate the extrapancreatic inflammatory manifestations of this syndrome.

Comparison of azathioprine, methotrexate, and the combination of both in the treatment of rheumatoid arthritis. A controlled clinical trial.

OBJECTIVE: To compare the relative safety and efficacy of azathioprine (AZA), methotrexate (MTX), and the combination of both in the treatment of active rheumatoid arthritis (RA). METHODS: Two hundred twelve patients with active RA were entered into a 24-week prospective, controlled, double-blind, multicenter trial and were randomly assigned to 1 of 3 treatment groups. RESULTS: One hundred fifty-eight patients finished 24 weeks of the study. There were no remissions seen but response rates were greater than 30% for all outcome measures. Combination therapy was not statistically superior to MTX therapy alone, but both combination therapy and MTX alone were superior to AZA alone when patients were analyzed by intent-to-treat and with withdrawals treated as therapy failures. If only patients who continued taking the therapy were analyzed, the mean improvement was greater for AZA therapy than for MTX, while the combination remained the most active. Adverse effects on the gastrointestinal tract and elevations of liver enzyme levels were the most frequent causes for discontinuations. CONCLUSION: Both combination therapy and MTX alone were superior to therapy with AZA alone for active RA but were not statistically different in their effect on outcome assessment.