Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine. In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS. METHODS: One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit). Outcome measures included the number of positive tender points, the sum of pain threshold (kg/cm2 or "total myalgic score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale. RESULTS: The "total myalgic score" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference. Most VAS scores significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated. CONCLUSION: Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.

Leflunomide in psoriatic arthritis: a retrospective study of discontinuation rate in daily clinical practice compared with methotrexate.

OBJECTIVE: To assess the safety profile of leflunomide (LEF) in a two-year retrospective analysis of psoriatic arthritis (PsA) patients (pts) treated in daily clinical practice compared with methotrexate (MTX). PATIENTS: Fourty-two PsA patients with polyarticular involvement or asymmetrical oligoarticular arthritis, satisfying ESSG criteria for the spondyloarthropathies, treated with LEF monotherapy (10-20mg/die without loading dose) between September, 2004 and August, 2006 were reviewed. They were compared with MTX (7.5-15mg/week) users (44 cases). The adverse events (AEs) and the causes of withdrawal were evaluated. RESULTS: At 24 months, cumulative survival rate of pts remaining on drugs was 54.9% in LEF users and 57.0% in MTX users (p > 0.05). The discontinuation rate (DR) for toxicity was higher in LEF group (29.2%) than in MTX group (10.8%) (p = 0.07). The occurrence of AEs was more frequently registered in the first year in both groups. LEF monotherapy showed a significant higher crude incidence for any AEs (38.7 events x100 person-years) compared to MTX (14.3 events x100 person-years) (p < 0.001). The cumulative DR for inefficacy was greater but not statistically significant in MTX group than LEF (28.6% vs. 12.6% respectively; p = 0.056). Finally, DR for other causes accounted for 8.7% vs. 11.0% respectively (p > 0.05). CONCLUSIONS: Our data showed, in a setting of clinical practice, that the rate of PsA pts remaining on drug was comparable between LEF and MTX, and a manageable LEF safety profile during a 24 months of follow-up, even if a greater incidence of DR for AEs was registered than in MTX users.

[Metabolic syndrome in inflammatory rheumatic diseases]. / La sindrome metabolica nelle malattie reumatiche infiammatorie.

Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

[Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in clinical practice]. / Profilo di tollerabilità del methotrexate nell'artrite reumatoide: analisi retrospettiva su una coorte di pazienti ambulatoriali.

OBJECTIVE: To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or TNFalpha inhibitors and the incidence and typology of adverse events (AE) occurred in rheumatoid arthritis (RA) patients. METHODS: A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFalpha agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. RESULTS: The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with TNFalpha inhibitors, 75.7 person-years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. CONCLUSIONS: These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity.

[The arthropathy of systemic sclerosis]. / L'artropatia della sclerosi sistemica.

Joint involvement occurs in thirds of SSc patients during the course of the disease, but may be the onset manifestation. Arthralgias, stiffness and tendon sheath involvement constitute the most common clinical findings affecting all joints, but predominantly the fingers, wrists and ankles. The most common radiographic abnormalities in SSc patients are subcutaneous calcinosis and digital tuft resorptions, which are frequently observed at the hands. Juxtaarticular demineralisation, joint space narrowing and erosions also occur and are diagnostic challenges with rheumatoid arthritis. Flexion deformities and tendon friction rubs are more common in dcSSc; arthritis/arthralgias and radiographic abnormalities similarly affect patients from each subset. A recent classification of radiological patterns (inflammatory, degenerative, periarticular fibrotic) pointed out a greater prevalence of the fibrotic pattern at the hands and degenerative pattern at the feet.