Efficacy and safety of leflunomide in DMARD-naive patients with early rheumatoid arthritis: comparison of a loading and a fixed-dose regimen.

OBJECTIVE: To assess the efficacy of LEF administered with or without a loading dose in DMARD-naïve patients with early RA. METHODS: This multicentre, double-blind, randomized clinical trial included adults with RA diagnosed within 6 months (ACR criteria). Patients were randomly selected to receive either a 100 mg loading dose or a 20 mg fixed dose of LEF for 3 days, followed by a 3-month open-label maintenance period of 20 mg LEF qd. The primary outcome criterion was ACR20 response rate at study end in the intent-to-treat population. Secondary criteria were ACR20, ACR50, ACR70 and DAS28 response rates at 1 and 3 months and safety. RESULTS: The intent-to-treat population included 120 patients (median time since diagnosis 0.95 months). The ACR20 response rate at study end was 69.0% (95%CI 60.5%, 77.4%). Response rates were significantly lower (P = 0.025) in the loading-dose group [58.5% (45.2%, 71.8%)] than in the fixed-dose group [77.8% (67.5%, 88.0%)]. Three-month ACR50, ACR70 and DAS28 response rates were 41.4%, 17.7% and 81.7%, respectively, with no significant differences between groups. Adverse events occurred in 53.7% (loading-dose group) and 49.3% (fixed-dose group) of patients, most frequently diarrhoea and elevated hepatic enzymes; these occurred more frequently and earlier in treatment when the loading dose was used. CONCLUSION: LEF was effective in DMARD-naïve patients with early disease. No incremental benefit was observed with the use of a loading dose, which may be associated with an increased initial rate of adverse events. The advantage of LEF initiation with a loading dose is not confirmed in this population. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00596206.

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis.

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18-60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.

Shoulder impingement syndrome: correlations between clinical tests and ultrasonographic findings.

OBJECTIVES: To compare the diagnosis of shoulder impingement syndrome (SIS) established by clinical and ultrasonographic examination and to evaluate the value of clinical tests for SIS as well as for rotator cuff pathology. METHODS: One hundred patients with periathrophatia scapulohumeralis entered the study, including 64 females and 36 males aged between 20-84 years (mean 56.8 and 57.5, respectively). Clinical and ultrasonographic examinations were carried out by independent observers, a rheumatologist and a musculoskeletal-trained sonographer. Clinical tests for SIS and for each of the tendons of the rotator cuff, as well as static and dynamic ultrasonographic examinations were performed for both shoulders. Findings were compared and statistically analyzed. RESULTS: The Hawkins test (72.2%) proved to be the most sensitive clinical test for the identification of SIS and the Neer test (95.3%) was the most specific one. When four tests were simultaneously positive, the specificity for the diagnosis was 98.5% but the sensitivity decreased to 40.3%. Jobe's test indicated supraspinatus involvement with a specificity of 90% but it was not able to disclose the type of lesions. The sensitivity and specificity of the tests aiming to elicit infraspinatus tendon pathology were of low value whereas those addressing subscapularis tendon involvement were rather of moderate value. SIS was clinically correctly diagnosed in 80.5% of cases, but its characteristic stages were poorly recognized (stage I 50%, stage II 70%, and stage III 30.7%). CONCLUSIONS: Although clinical tests are insufficient for clinical diagnosis, the examination of the patient still plays an important role in rotator cuff disorders. Ultrasonography should be used for all patients suffering from painful shoulder in order to improve the diagnosis.

Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial.

OBJECTIVE: To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. METHODS: Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. RESULTS: A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. CONCLUSION: Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.

Fever of unknown origin-predictors of outcome. A prospective multicenter study on 164 patients.

BACKGROUND: To date, the studies that have been done on fever of unknown origin have mostly been descriptive. Therefore, we know the etiogical spectrum and how it has changed since 1966 for many regions of the world. However, we do not know if there are clinical or laboratory predictors of severe outcome. Being able to estimate the severity of the disease early on would allow one to determine how intensive the diagnostic work-up should be. METHODS: A multicenter cohort study was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. The study lasted 2 years (1997-1998) and included a follow-up period of another 2 years. The main outcome measured was the final diagnosis established at the end of follow-up. RESULTS: When the white cell count was abnormal, the relative risk for a serious disease was 1.49 (CI: 1.15-1.94; p=0.004), when anemia was present, the relative risk was 1.55 (CI: 1.21-1.98; p=0.003), and for high alanine aminotransferase (ALAT), bilirubin, or lactate dehydrogenase (LDH), the relative risks were 1.57 (CI: 1.21-2.02; p=0.010), 1.57 (CI: 1.18-2.08; p=0.007), and 3.43 (CI: 1.81-6.48; p=0.0002), respectively. In multivariate analysis, the odds ratios for serious diseases were 2.7 (CI: 1.17-6.4; p=0.02) for abnormal white cell count, 2.8 (CI: 1.14-7.16; p=0.02) for anemia, 4.3 (CI: 1.6-11.5; p=0.003) for high serum bilirubin, and 5.3 (1.5-18.6; p=0.009) for high serum ALAT. CONCLUSIONS: In patients having a fever of unknown origin, anemia, abnormal white cell count, and high ALAT and bilirubin are independent predictors of severe outcome.