Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid arthritis: real-world data from a university centre registry.

OBJECTIVE: This study aimed to investigate the efficacy, safety and survival of TNF-α inhibitors in patients with RA. METHODS: A total of 178 patients >18 years of age were treated with TNF-α inhibitors. A total of 74 patients were treated with infliximab, 75 with adalimumab and 29 with etanercept. Each patient was followed-up for a period of 8 years. RESULTS: Anti-TNF-α therapy resulted in rapid clinical improvement. The rate of good/moderate response according to EULAR response criteria for the index 28-joint DAS with CRP in the first 6 months was 82% for infliximab, 89.6% for adalimumab and 95.6% for etanercept. The rate of withdrawal in 8 years was 80% for patients on infliximab, 61.4% for patients on adalimumab and 47.6% for patients on etanercept. The main reasons for discontinuation were allergic reactions for infliximab (rate of discontinuation 25.7%) and inefficacy for adalimumab and etanercept (17.5% and 23.8%, respectively). Systemic allergic reactions and infections were significantly more frequent in the infliximab group (P < 0.05 and P < 0.001, respectively). However, there was no significant difference among the three drugs concerning serious infections. According to Kaplan-Meier survival analysis, a significantly faster withdrawal for infliximab patients was depicted compared with adalimumab (P = 0.003) and etanercept (P = 0.019), while adalimumab and etanercept were not statistically different (P = 0.089). CONCLUSIONS: TNF-α inhibitors establish an effective therapeutic option in RA showing an acceptable safety profile. Infections and allergic reactions appear more often with infliximab, while serious infections did not differ among them. RA patients treated with infliximab are more likely to discontinue treatment earlier compared with the other alternatives.

Transcription regulatory polymorphism -43T>C in the 5'-flanking region of SLC19A1 gene could affect rheumatoid arthritis patient response to methotrexate therapy.

The reduced folate carrier (RFC) protein (SLC19A1-gene) has central role in the uptake and intracellular accumulation of folates. In this respect, we investigate whether SLC19A1 genetic variations could affect rheumatoid arthritis (RA) patient response to antifolate treatment. One hundred six unrelated RA patients were enrolled in this study. Polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) was used as the screening method for genetic variants. Unusual SSCP patterns were characterized by direct sequencing of the PCR products and subsequently restriction assays were established. Western blot analysis of RFC protein was performed in respect of the identified SLC19A1 genotypes. Patient response to methotrexate (MTX) was evaluated using disease activity for 28 joint indices score, American College of Rheumatology 20% and 50% scores. No mutation was found in the SLC19A1 gene, but three polymorphic variants: the -43T>C in the 5'-flanking sequence to the ATG-transcription start site; and the 80G>A (R27H) and 696C>T (P232P) in the coding gene sequence. The wild type alleles of the three polymorphisms were in strict linkage disequilibrium. Western blot analysis revealed that the non-wild type allele of polymorphism -43T>C is associated with low RFC protein expression levels. Furthermore, the genotypic analysis of the functional polymorphic variant -43T>C revealed to be insufficient to predict patient response to MTX therapy. According to recent literature, several transport systems account for folate membrane transport. Additionally, in previous studies discrepancies have been reported to exist between the same genetic variants and their use in prediction of patient response to MTX therapy. Therefore, the present genotypic-phenotypic association study of a functional polymorphism revealed the need of a complex genotypic analysis in order to predict patient response to folate antagonists' therapy.

Persistent clinical response of infliximab treatment, over a 4-year period in ankylosing spondylitis.

Our aim was to investigate the efficacy, toxicity, and drug discontinuation in patients with ankylosing spondylitis (AS) treated with infliximab. Thirty-five patients with AS, who were enrolled between June 2001 and December 2002 were treated with infliximab. All patients fulfilled the New York revised criteria for AS and had axial disease. Infliximab (5 mg/kg weight), was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter. If this failed to give an acceptable treatment response, the interval was shortened to 6 or 4 weeks. The patients were followed-up at predefined times according to a standardized protocol. Data concerning infliximab efficacy, tolerability, adverse events, interval, and drug discontinuation were all recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and the Ankylosing Spondylitis Assessment Study group (ASAS) 40%, and ASAS 5/6 response criteria were recorded. Infliximab treatment resulted in a rapid improvement in the BASDAI and ASAS scores in the first year of the treatment, which sustained throughout the fourth year. More specifically, after the third year of treatment 17/35 (48.6%) of patients achieved BASDAI 50% response criteria, 19/35 (54.3%) attained the ASAS 40% and 15/35 (42.9%) reached the ASAS 5/6. After the fourth year of treatment BASDAI 50% was reached by 17/35 (48.6%) of patients, ASAS 40% by 17/35 (48.6%), while ASAS 5/6 was attained by 15/35 (42.9%). The clinical improvement was associated with the reduction of acute phase reactants as measured by C-reactive protein levels. After the first year of treatment, the "survival rate" of infliximab was 94.3%, after the second year was 91.4%, after the third year was 85.7% and even after 4 years of treatment still maintained high 77.9%. Six (17.1%) patients were withdrawn during the observational period. Three because of lack of efficacy, two because of allergic reactions and one lost from follow-up. Infliximab was effective, safe, and well tolerated in patients with AS. The clinical response was maintained for a period of 4 years and over, with infliximab survival of 77.9%.