The effect of interleukin-1 blockade on fatigue in rheumatoid arthritis—a pilot study

Fatigue occurs in many patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases and may be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion. It can be restrictive and severely disabling. We recently found more than 3/4 of systemic lupus erythematosus patients to be significantly affected by this phenomenon. We hypothesized that fatigue in patients with RA might be comparable to sickness behavior in animals possibly caused by disturbances in interleukin-1 beta signaling pathways and thus accessible to blockade by biologic agents. This study compared measures of disease behavior and fatigue symptoms in eight RA patients before and at three time points during treatment with daily administration of anakinra.     

Leflunomide in dialysis patients with rheumatoid arthritis—a pharmacokinetic study

Pharmacokinetic data of disease modifying antirheumatic drugs during hemodialysis are limited to sulfasalazine, methotrexate, and cyclosporine. Only respective anecdotal data have been reported on leflunomide. We repeatedly measured teriflunomide (A77-1726), the active metabolite of leflunomide, during standard hemodialysis sessions and calculated teriflunomide clearances in five patients with rheumatoid arthritis (RA) and end-stage renal disease. The calculated teriflunomide clearances during a standardized dialysis session of 3–4.5 h at a blood flow rate of 160–300 ml/min were between 0 and 4.3 ml/min, the mean clearances of the total dialysis ranged between 1.1 and 3.4 ml/min. Total amount of teriflunomide removed was 5.8–8.8 μg per dialysis session. Dialytic removal of the active metabolite of leflunomide, teriflunomide (A77-1726), is negligible. Leflunomide can be used for RA patients on chronic dialysis without any dosage modification.     

Leflunomide in the treatment of patients with early rheumatoid arthritis—results of a prospective non-interventional study

Leflunomide is effective and well tolerated in the treatment of rheumatoid arthritis (RA), however, data on its use in early RA are scarce. This study seeks to evaluate effectiveness and safety of leflunomide in the treatment of early RA in daily practice. This prospective, open-label, non-interventional, multi-center study was carried out over 24 weeks including adults with early RA (≤1 year since diagnosis). Leflunomide treatment was according to label instructions. Three hundred thirty-four patients were included. Disease activity score in 28 joints (DAS28) response (reduction in DAS28 of >1.2 or reduction of >0.6 and a DAS28 of ≤5.1) was 71.9% at week?12 and 84.6% at week 24. 25.0% of patients achieved clinical remission (DAS28?≤?2.6). Most frequently reported adverse drug reactions (ADR) were diarrhea (3.0%), nausea (2.4%), hypertension (1.8%), and headache (1.5%). Serious ADR were reported in four patients (1.2%). Leflunomide showed the effectiveness which was to be expected from controlled studies without revealing any new or hitherto unknown side effects. Onset of action was quick and significant improvement of disease was seen after 12 weeks of therapy and at even higher rates after 24 weeks irrespective of the use of a loading dose. Interestingly, the DAS28-remission rate achieved was similar to the rate seen with methotrexate or biologic therapy in other studies.     

A Tunisian case–control association study of a 6q polymorphism in rheumatoid arthritis

Rheumatoid arthritis (RA), the most common autoimmune inflammatory disease of the joints, is a multifactorial disease, involving both genetic and environmental risk factors. TNFAIP3 (tumor necrosis factor, alpha-induced protein 3) gene located in a region of genetic susceptibility in RA is an attractive candidate to be involved in autoimmunity disorders. Our aim was to test the single nucleotide polymorphism rs6920220 located near TNFAIP3 in a case-control study in Tunisian population. The rare allele rs6920220-A was reported to have a risk effect on RA in several genome-wide association studies. Our results revealed a trend of an association of rs6920220-A allele with RA and genotypes containing this allele were in a higher proportion in RA patients than in matched controls. These findings have to be confirmed by a replication in largest RA and control groups of the same ethnic origin. TNFAIP3 gene may have a key role in autoimmunity through its action as a negative regulator of the NF-κB pathway. Further functional investigations are required to understand the mechanism by which this gene is involved in the RA pathogenesis.     

Association of Rsa polymorphism of the estrogen receptor-β gene with rheumatoid arthritis

To investigate the possible influence of the single nucleotide polymorphism (SNP) of the estrogen receptor-β gene, rs1256049 (Rsa) in exon 5, on the frequency of rheumatoid arthritis (RA), 263 RA patients and 174 control subjects with osteoarthritis (OA) were recruited. Rsa polymorphism was detected using a PCR–RFLP, Polymerase Chain Reaction—Restriction Fragment Length Polymorphism method. The occurrence of both mutant allele (G) and genotype (GG) were significantly higher in RA than in OA patients (allele P?=?0.008, OR: 1.501, 95%CI: 1.12–2.02). In RA patients, GG genotype frequency was higher in severe RA patients than mild RA patients. Moreover, there was significant difference between severe RA patients and OA patients (P?=?0.009), also the allele distribution was significant different between severe RA, mild RA, and OA patients (P?=?0.025, 95%CI?=?0.61–0.93). With respect to gender, GG genotype was statistically more frequent in female RA patients than that of OA, while such an association was not observed in men. Above all, the presence of the GG genotype could be a risk factor for RA and such trend might be different in gender, although additional larger scale study is needed.     

Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke—a cross-sectional study

Specific data regarding the full range of stroke outcomes among patients with rheumatoid arthritis (RA) are lacking. This study aimed to investigate outcomes in RA patients hospitalized for a stroke. The study retrieved data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 26,336 patients who were hospitalized for stroke treatment. Of these patients, 736 patients with a prior diagnosis of RA before the index hospitalization were selected as the study group. We selected 2208 age–sex-matched patients without RA as the comparison group. We performed conditional logistic regressions to calculate odds ratios (ORs) for in-hospital mortality and secondary diagnoses of pneumonia, urinary tract infections (UTIs), peptic ulcers, acute respiratory failure, and the use of mechanical ventilation to compare RA patients and comparison patients. We also compared the length of stay (LOS) and hospitalization costs between patients with RA and comparison patients. We found that RA patients had a significantly increased risk of peptic ulcer during the stroke hospitalization (OR?=?1.52, 95% CI?=?1.05–2.20). However, there were no significant differences between patients with RA and comparison patients in terms of in-hospital mortality, pneumonia, UTIs, acute respiratory failure, or the use of mechanical ventilation. Furthermore, the LOS of stroke hospitalization did not differ between the two groups. We concluded that RA patients hospitalized for a stroke do not have a significantly different risk of in-hospital mortality, pneumonia, UTIs, and mechanical ventilator use, but they have a higher risk of peptic ulcers. Additionally, among patients with a subarachnoid/intracerebral hemorrhagic stroke, RA patients were more likely to have received mechanical ventilation than comparison patients (adjusted OR?=?1.89, 95% CI?=?1.14–3.15).     

Tumour necrosis factor a −308 promoter polymorphism in patients with rheumatoid arthritis

There are controversial reports that TNF-a promoter polymorphism may be an independent marker of susceptibility to rheumatoid arthritis (RA). We used Polymerase chain reaction amplification and Restriction fragment length polymorphism for analysis of the polymorphism at position -308 in promoter of TNF-α gene in 34 patients with RA and 30 healthy individuals. Distribution of TNF-genotypes in RA patients did not differ from that in controls. Moreover, there was apparent association between the -308 TNF-α polymorphism and erosions in hand x-Ray was found (P value = 0.043). We suggest that TNF-α -308 promoter polymorphism is not a genetic risk factor for RA susceptibility but may be associated with radiographic damage in rheumatoid patients. All work was funded by the Chancellor for Research of Mashhad University of Medical Science.     

Dose tapering of biologic agents in patients with rheumatoid arthritis—results from a cohort study in Germany

Clinical Rheumatology - To assess the association of demographic and clinical factors with the clinical decision of tapering biologic disease modifying antirheumatic drugs (bDMARDs) in patients...     

Pharmacoeconomic analysis of Metoject(®) in the treatment of rheumatoid arthritis in Spain

ObjectivesThe aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject^®) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain.MethodsA cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied.ResultsThe cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject^® went from 25,173 to 35,807 € at 5 years and from 19,056 to 25,351 € for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175 €/QALY gained, and for patient lifetime from 22,514 to 29,848 €/ QALY gained.ConclusionsAdditional costs of Metoject^® with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject^® could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.     

Correction to: Risk of adverse outcomes in patients with rheumatoid arthritis hospitalized for stroke—a cross-sectional study

Clinical Rheumatology - The authors of the published version of this article incorrectly presented the affiliation of Li-Chin Sung. The revised affiliation is now presented correctly in this article.     

Association of the ?1082 G/A promoter polymorphism of interleukin-10 gene with the autoantibodies production in patients with rheumatoid arthritis

Interleukin-10 (IL-10) is an immunoregulatory cytokine, usually considered to mediate the downregulation of the inflammatory response in rheumatoid arthritis (RA). Some effects of IL-10 are not anti-inflammatory; for example, the activation of B cells to promote autoantibody production. Allelic polymorphisms located in the promoter region of the IL-10 gene may contribute to the regulation of autoantibodies production. To examine the putative association between the −1082 G/A polymorphism in the promoter region of the IL-10 gene and the susceptibility to disease onset and severity of RA, a total of 144 patients with RA diagnosed according to the revised criteria of the American College of Rheumatology for RA were consecutively recruited into the study. Radiographic progression of RA was scored according to the Sharp/van der Heijde method. Serum levels of rheumatoid factors (RFs) were measured by enzyme-linked immunosorbent assay. Polymerase chain reaction amplification was used for the analysis of the promoter polymorphism of the IL-10 gene. We observed significant differences in genotype distribution of the −1082 G/A polymorphism between IgM RF, IgA RF, and IgG RF positive/negative subgroups of RA patients, with higher prevalence of the GG genotype within IgM RF (P _g = 0.006), IgA RF (P _g = 0.05), and IgG RF (P _g = 0.007) negative RA patients. Results obtained in this study provide the evidence of an association between the −1082 G/A polymorphism in the IL-10 gene promoter and the production of RFs in RA patients.     

Clarithromycin in rheumatoid arthritis: the addition to methotrexate and low-dose methylprednisolone induces a significant additive value—a 24-month single-blind pilot study

To compare the efficacy of the addition of clarithromycin (CM) to methotrexate (MTX) and methylprednisolone (MP) in active rheumatoid arthritis (RA). 32 patients with RA consecutively randomized. Control group: sixteen patients treated for 24 months with MTX 10–15 mg i.m. weekly and MP 4–6 mg daily. CM group: sixteen patients treated with MTX 10–15 mg i.m. weekly and MP 4–6 mg daily for 24 months; CM therapy added in the first month (500 mg twice a day for the first 15 days followed by 500 mg a day for the remaining 15 days). Evaluation of the improvement following ACR criteria was performed at months 1 (primary endpoint), 3 and 6. Patients were furthermore observed after 12, 18 and 24 months from the study beginning. At month 1, following ACR70 improvement criteria, we found a significant additive value in CM group (10/16 = 63 % vs 4/16 = 25 %, p = 0.033—chi-square test). After discontinuation of CM, the difference between groups was anymore evident (month 3: CM group 10/16 = 63 % vs control group 9/16 = 56 %). At month 24, 7/16 (44 %) in control group and 12/16 (75 %) in CM group completed the follow-up. The addition of CM to MTX and MP can induce the remission ACR 70 in the majority of RA patients within 4 weeks, while MTX and MP alone need about 3 months to achieve the same result.     

No relationship of −627 interleukin-10 promoter polymorphism in Chinese patients with rheumatoid arthritis

Abstrtact The aim of this study was to examine whether –627 interleukin-10 (IL-10) promoter polymorphism is a marker of susceptibility to or severity of rheumatoid arthritis (RA) in Chinese patients in Taiwan. The study included 198 Chinese patients with RA. One hundred unrelated healthy individuals living in central Taiwan served as the control subjects. The relationship between IL-10 gene polymorphism and clinical manifestations of RA was evaluated. For the genotype, allelic frequency, and carriage rate of IL-10 polymorphism, there were no statistically significant differences found between patients and controls. Furthermore, we did not detect any association of IL-10 genotype with rheumatoid factor (RF), extra-articular involvement, or bone erosion in the RA patients. The lack of association of –627 IL-10 gene polymorphism with RA and the clinical findings in our study implies that the IL-10 gene polymorphism cannot serve as a candidate gene marker for screening RA patients.     

Allelic frequency of the MCP-1 promoter −2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis

Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene −2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the −2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the −2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the −2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.     

Association of cytosine–adenine repeat polymorphism of the estrogen receptor-β gene with rheumatoid arthritis symptoms

The influence of the polymorphism of the estrogen receptor-β gene, cytosine–adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE^® DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established: ≤21 repeats (short S), ≥22 repeats (long L); and 3 kinds of genotypes (SS, SL, LL) were found. In RA patients, the L allele frequency was higher (OR = 2.03; P ≤ 0.05 Fisher’s test) and more subjects carried the LL genotype (OR = 5.50; P ≤ 0.05 Fisher’s test) compared to OA patients. It was concluded that the presence of the L allele could be a risk factor for RA, although additional larger scale study is needed.     

Dietary intake and risk of rheumatoid arthritis—a cross section multicenter study

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student’s t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518–0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981–0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867–0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.     

Quality of life and functional capacity in patients with rheumatoid arthritis – Cross-sectional study

Objectives

To analyze the Health related Quality of Life (HRQoL) and physical function in rheumatoid arthritis (RA) patients and compare it with the general population. We also intended to analyze about disease activity influence in HRQoL and functional capacity, as well as determine potential determinants for these outcomes.