Long-term methotrexate use in rheumatoid arthritis patients: real-world data from the MARTE study.

BACKGROUND: The MARTE study investigated the demographic, clinical, and therapeutic characteristics of rheumatoid arthritis (RA) patients ongoing methotrexate (MTX) treatment for longer than 8 years. METHODS: This cross-sectional, observational study considered 587 RA patients from 67 Rheumatology Units across Italy. Data collected included demographic, clinical, and therapeutic characteristics, focusing on MTX prescription patterns (route of administration, dosing regimens, treatment duration, and discontinuation). RESULTS: As initial therapy, 90.6% of patients received one conventional synthetic Disease Modifying Anti Rheumatic Drug (csDMARD), with treatment started within the first 3 months from diagnosis in half of the patients. MTX was the first csDMARD in 46.2% of patients. The prevalent route of administration at diagnosis was the intramuscular (60.5%), while at study entry (baseline) 57.6% were receiving subcutaneous MTX. Patients who required a higher MTX dose at study entry were those who received a significantly lower starting MTX dose (P<0.001). Significantly higher MTX doses were currently required in men (P<0.001), current smokers (P=0.013), and overweight patients (P=0.028), whereas patients on oral therapy received significantly lower doses of MTX (P<0.001). CONCLUSIONS: The MARTE study confirms once again the potential of the proper use of MTX in the treatment of RA. Data from our study suggest that a higher dose of MTX should be used since the first stages in overweight patients, men, and smokers.

Adherence to current recommendations on the use of methotrexate in rheumatoid arthritis in Italy: results from the MARI study.

OBJECTIVES: The aim of this study was to assess how the management of rheumatoid arthritis (RA) with methotrexate (MTX) in Italy is adherent to current national recommendations. METHODS: We performed a cross-sectional and retrospective analysis of data collected from the MARI study, a multicentre survey on Italian patients with RA on treatment with MTX for at least 12 months. Retrospective data included patient's clinical history, previous treatment with MTX, screening tests performed before MTX prescription. Cross-sectional data were collected about current treatment with MTX, concomitant medications, and disease activity. Each proposition of the 2013 Italian recommendations on the use of MTX in RA was reformulated in terms of audit criteria, and adherence to provided indications was evaluated for every patient. RESULTS: Among the 1336 included patients, less than 40% had started treatment with MTX within 3-6 months from the diagnosis and nearly 30% of them were prescribed with an initial dose of MTX between 12.5 and 15 mg/week. Screening for HBV and HCV infection as well as chest x-ray was performed in a proportion of patients around 60% and more than 90% of them underwent lab tests before MTX prescription and regularly throughout the treatment. Folic acid supplementation was given at recommended dosages in a high proportion of patients. CONCLUSIONS: Our survey showed a good adherence of Italian rheumatologists to recommendations regarding safety issues with MTX in RA, but a suboptimal approach in terms of time and dosage of the treatment in the early phases of the disease.

Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype.

CONTEXT: Mandibuloacral dysplasia type A (MADA; OMIM 248370) is a rare progeroid syndrome characterized by dysmorphic craniofacial and skeletal features, lipodystrophy, and metabolic complications. Most Italian patients carry the same homozygous missense mutation (p.R527H) in the C-terminal tail domain of the LMNA gene, which encodes lamin A/C, an intermediate filament component of the nuclear envelope. OBJECTIVE: The objective of the study was to identify novel LMNA mutations in individuals with clinical characteristics (bird-like facies, mandibular and clavicular hypoplasia, acroosteolysis, lipodystrophy, alopecia) observed in other well-known patients. DESIGN: The LMNA gene was sequenced. Functional properties of the mutant alleles were investigated. PATIENT: We report a 27-yr-old Italian woman showing a MADA-like phenotype. Features include a hypoplastic mandible, acroosteolysis, pointed nose, partial loss of sc fat, and a progeric appearance. Due to the absence of clavicular dysplasia and normal metabolic profiles, generally associated with muscle hyposthenia and generalized hypotonia, this phenotype can be considered an atypical laminopathy. RESULTS: We identified a patient compound heterozygote for the p.R527H and p.V440M alleles. The patient's cells showed nuclear shape abnormalities, accumulation of pre-lamin A, and irregular lamina thickness. Lamins A and C showed normal expression and localization. The electron microscopy detected heterochromatin defects with a pattern similar to those observed in other laminopathies. However, chromatin analysis showed a normal distribution pattern of the major heterochromatin proteins: heterochromatin protein-1beta and histone H3 methylated at lysine 9. CONCLUSIONS: The clinical and cellular features of this patient show overlapping laminopathy phenotypes that could be due to the combination of p.R527H and p.V440M alleles.