ABSTRACT
OBJECTIVE: To analyse the safety of leflunomide plus infliximab combination therapy, in adult rheumatoid arthritis (RA) patients. PATIENTS: A retrospective study of 17 adult patients with active RA (DAS 28 = 5.94 +/- 0.88 at baseline) who were treated with a combination of leflunomide plus infliximab after failure of treatment with other DMARDs. 13 patients were treated for a minimum of 3 months with leflunomide without toxicity before beginning infliximab. Treatment was begun simultaneously with both drugs in 4 patients. Side effects (clinical and biological) and efficacy (DAS 28) were evaluated at each infliximab infusion (3 mg/kg at week 0, 2, 6 and then every 8 weeks). RESULTS: Thirteen patients experienced 20 types of side effects and 8 of them stopped the combination therapy. The causes of discontinuation were congestive heart failure (1 case), hypertension with thoracic pain (2 cases), eczematous skin patches (2 cases) and neutropenia (3 cases). No death was registered. Nine RA patients continuted the therapy with a median follow-up of 22 weeks. Only 4 of them experienced no side effects. Eight patients were positive for antinuclear antibodies (ANA) and 1 for double-stranded DNA (dsDNA) antibodies at study entry. After treatment, 13 and 5 patients tested positive respectively for ANAs and dsDNA antibodies. There was no relationship between discontinuation and ANA/dsDNA positivity. CONCLUSION: In this cohort, adverse events were not very different from those seen in patients on either treatment alone and the combination of leflunomide plus infliximab did not appear to be as badly tolerated as described in a previous study.
Subject(s)
Adjuvants, Immunologic/adverse effects , Antibodies, Monoclonal/adverse effects , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Isoxazoles/adverse effects , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear/blood , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/physiopathology , Drug Therapy, Combination , Female , Humans , Infliximab , Leflunomide , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Withholding TreatmentABSTRACT
A strong association between an interferon gamma (IFN-gamma) gene polymorphism and rheumatoid arthritis susceptibility and severity has been reported in a case-control study. We investigated this polymorphism in 103 patients with early rheumatoid arthritis and 130 controls. Severity of rheumatoid arthritis was measured after 4-year follow-up with a validated radiographic score. The median radiographic score in patients increased from 1 (IQR 0-4) to 11.5 (2-35) over the 4-year follow up. The distribution of IFN-gamma alleles did not differ between patients and controls, and the distribution of radiographic scores did not differ among patients carrying the different IFN-gamma alleles. We have failed to confirm the association between the IFN-gamma gene polymorphism and rheumatoid arthritis susceptibility or severity.
Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease , Interferon-gamma/genetics , Alleles , Arthritis, Rheumatoid/classification , Case-Control Studies , Female , Humans , Male , Middle Aged , Polymorphism, Genetic , Severity of Illness IndexSubject(s)
Hip Joint/pathology , Synovitis/pathology , Acute Disease , Aged , Female , Follow-Up Studies , Humans , Male , Pain/etiologySubject(s)
Myositis Ossificans/pathology , Adolescent , Anti-Inflammatory Agents/therapeutic use , Arm/pathology , Diphosphonates/therapeutic use , Female , Humans , Humerus/diagnostic imaging , Humerus/injuries , Myositis Ossificans/diagnostic imaging , Myositis Ossificans/drug therapy , Pamidronate , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: To test if interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in rheumatoid arthritis (RA). METHODS: The study included 108 patients with early RA followed up for 2 years and 128 healthy controls. From genomic DNA, 6 polymorphisms in genes for IL-1beta, IL-1Ra, IL-10, and IL-4 were typed. Allelic frequencies and carriage rates were compared between RA patients and controls, between patients with erosive and nonerosive RA, and between patients with or without sustained remission. RESULTS: The RP1 allele of the IL-4 gene was found with a significantly higher frequency in RA patients compared with controls. The combination of an RA-related HLA-DR allele expressing shared epitope and the presence of allele E2 in IL-1beta exon 5 was found to expose patients to an increased risk of erosive disease, with an odds ratio of 8.20 (95% confidence interval 2.59-25.84, P < 0.0001). No significant association was observed between polymorphisms and the occurrence of sustained remission. CONCLUSION: This report, for the first time, indicates an association between RA and a polymorphic IL-4 gene sequence located in 5q31-33. In addition, the results show the prognostic value of a polymorphism in IL-1beta exon 5, which allowed prediction of erosive disease with a specificity of 91.8% in 42.1% of patients. Although these observations are very interesting, they have to be considered preliminary and will need to be confirmed.
