European League Against Rheumatism Response Criteria Research Articles

Evaluation of the efficacy and safety of a herbal formulation for rheumatoid arthritis – A non-inferiority randomized controlled trial

Ethnopharmacological relevanceRheumatoid arthritis (RA) is a diverse disease characterized by a variable, progressive course of articular and extra-articular symptoms that are linked with pain, disability, and mortality. The exact cause of rheumatoid arthritis is still being investigated, and there is no cure for this debilitating, persistent, painful disease. Qurs-e-Mafasil, a herbal Unani preparation, is regarded as a potent treatment for Waja'al-Mafasil, a condition clinically similar to rheumatoid arthritis, but scientific evidence is scarce. Aim of the studyThis study aimed to assess the non-inferiority of Qurs-e-Mafasil compared to celecoxib in the treatment of patients with rheumatoid arthritis. Materials and methodsThis randomized controlled trial was conducted on seventy patients diagnosed with rheumatoid arthritis between the ages of 35 and 55 years. The participants were randomly allocated in a ratio of 3:2, with 42 participants in the test group and 28 participants in the control group. The test group was administered 2 tablets (each having 500 mg) of Qurs-e-Mafasil, while the control group was administered 1 capsule of Celecoxib 100 mg. Both medications were delivered for four weeks. The primary outcome measure was European League Against Rheumatism (EULAR) response criteria based on Disease Activity Score-28 (DAS28) assessed before and after therapy, whereas the secondary outcome measure was the change in joint pain severity as determined by a 100 mm Visual Analog Scale (VAS) at baseline and each follow-up. The safety of the interventions was evaluated based on adverse event monitoring at each follow-up and laboratory tests including hemogram, Liver Function Tests (LFTs), Kidney Function Tests (KFTs), and a complete urine examination performed at baseline and after four weeks of treatment. ResultsThe per-protocol analysis was done on 50 participants (30 in test group and 20 in control group) who completed the study duration. Thus, at the conclusion of the trial, participants in the test and control groups had either a moderate or no response based on EULAR response criteria. The odds ratio for no response versus moderate response between the test and the control groups was 0.71 (95% CI: 0.20–2.55) with p = 0.744. Moreover, the observed mean differences in VAS scores between the test and the control groups at 1st, 2nd, 3rd, and final follow-up were −0.33 (95% CI: −6.65 to 5.99, p = 0.916), 0.50 (95% CI: −5.63 to 6.63, p = 0.870), 2.42 (95% CI: −2.95 to 7.78, p = 0.370), and 3.00 (95% CI: −1.82 to 7.84, p = 0.219), respectively. ConclusionsThe differences in primary and secondary outcomes between the two groups indicate that Qurs-e-Mafāsil, a herbal Unani formulation containing Zingiber officinale Roscoe rhizome, Colchicum luteum Baker root, Piper nigrum L. fruit, and Withania somnifera (L.) Dunal. root, is comparable to celecoxib in the treatment of rheumatoid arthritis.

Evaluation of Response Criteria in Rheumatoid Arthritis Treated With Biologic Disease-Modifying Antirheumatic Drugs.

Biologic disease-modifying antirheumatic drugs (bDMARDs) used for rheumatoid arthritis (RA) treatment have several mechanisms of action. Interleukin-6 inhibitors (IL-6i) block the production of acute-phase reactants (APRs), which are some of the composite measures of disease activity. We undertook this study to examine the agreement between the European League Against Rheumatism (EULAR) response based on the erythrocyte sedimentation rate (ESR) or C-reactive protein level, the Simplified Disease Activity Index 50% response measure (SDAI50), and the Clinical Disease Activity Index 50% response measure (CDAI50) in patients treated with IL-6i and other bDMARDs. We enrolled 306 patients with RA who started or switched bDMARDs. Treatment response at 6 months was analyzed. Kappa statistics were used to evaluate the agreement between different response measures. The contribution of APRs to improvement in disease activity scores was examined. The change of Health Assessment Questionnaire (HAQ) score was analyzed in IL-6i-treated patients. Good agreement was achieved between response measures, with κ >0.6 in patients treated with tumor necrosis factor inhibitors or cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein. In IL-6i-treated patients, the agreement was low between the EULAR response (ESR) and the SDAI50 or the CDAI50 (κ = 0.43 and 0.37, respectively). Under IL-6i treatment, APR improvement accounted for 56.0% of total improvement of the Disease Activity Score in 28 joints (DAS28) using the ESR. When discordance was found between the CDAI50 and EULAR response in IL-6i-treated patients, all patients were classified as EULAR-only responders; there was no HAQ improvement in EULAR-only responders. EULAR response criteria overestimate the response under IL-6i treatment because the APR improvement largely contributes to the DAS28 improvement.

Investigation of the predictors of the response to Iguratimod therapy: A post-hoc analysis of post-marketing surveillance study

Objectives: The treatment response according to patient disease activity during Iguratimod therapy for rheumatoid arthritis has not been sufficiently assessed. A post-hoc analysis of post-marketing surveillance was performed. The treatment effect was evaluated using the European League against Rheumatism (EULAR) response criteria.Methods: Disease Activity Score (DAS) 28 was assessed at various time points. Patients showing a moderate or good response according to the EULAR response criteria at 24 weeks after the start of Iguratimod therapy were considered Responders. Propensity score matching was also performed, after which the factors with the greatest effect on the treatment evaluation were investigated.Results: The mean DAS28 at the start of administration and after 24 weeks was 4.31 and 2.52, respectively, in the Responder and 3.48 and 3.48, respectively, in the Non-responder. After propensity score matching for patient characteristics, the primary factors found to be related to being a Responder were concomitant use of methotrexate (MTX) with Iguratimod, and prior treatment with MTX before the start of Iguratimod.Conclusion: As factors related to the treatment effect, the concomitant use of MTX may contribute to achieving a better effect, and this study has shown that real-world are consistent with the results of clinical trials.

Radiological patterns of pulmonary involvement may predict treatment response in rheumatoid arthritis: A retrospective study.

There have been no reports on the relationship between lung radiological patterns and rheumatoid arthritis (RA) disease activity or RA treatment response in patients with RA-associated lung disease (RA-LD). Patients with RA-LD who underwent treatment for RA from April 2005 to March 2015 were retrospectively evaluated. RA-LD patients were divided into three groups based on high-resolution computed tomography (HRCT) patterns [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and bronchiolitis]. The disease activity score of 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the response of RA to treatment, as measured by the European League Against Rheumatism (EULAR) response criteria, were investigated. A total of 77 patients (21 with UIP, 23 with NSIP, and 33 with bronchiolitis) were enrolled. Median scores (interquartile range) on the DAS28-ESR at baseline were 5.27 (4.76-5.74), 5.48 (4.24-6.34), and 5.04 (3.90-5.66) for UIP, NSIP, and bronchiolitis, respectively; there were no statistical differences between the three groups (p = 0.412). One year after baseline, 19 (90%), 14 (61%), and 19 (58%) of patients in the UIP, NSIP, and bronchiolitis groups, respectively, were considered good or moderate responders, as evaluated using the EULAR response criteria; there was a significant difference between these three groups (p = 0.014). Multiple logistic regression analysis revealed that the UIP pattern was significantly associated with good or moderate response to RA treatment 1 year after baseline (p = 0.012). These results suggest that NSIP and bronchiolitis HRCT patterns may be risk factors for resistance to RA therapy.

High Proportion of Subjective Component to the Disease Activity Score is Associated with Favorable Response to Abatacept in Rheumatoid Arthritis.

BackgroundResponse prediction of certain biologic agents for the treatment of rheumatoid arthritis (RA) remains an unmet need in real-world clinical practice. The contribution of patient-reported components to the 28-joint Disease Activity Score (DAS28) was termed DAS28-P and investigated as a predictor of response to biologic agents, mostly tumor necrosis factor inhibitors. We aimed to evaluate DAS28-P as a predictor of the European League Against Rheumatism (EULAR) response to abatacept in patients with RA.MethodsThe study population was a prospective, observational, multicenter cohort of Korean patients with RA, who were followed up for a nationwide post-marketing surveillance study of abatacept. Correlation of DAS28-P with DAS28, change of DAS28, and EULAR response groups were evaluated. Logistic regression analysis was used to predict good-to-moderate EULAR response to abatacept in the study population.ResultsA total of 341 patients were involved in the analysis stratified on the EULAR response criteria. Presence of comorbidities, previous exposure to biologic agents, baseline DAS28, three of its components (tender joint counts, global health visual analog scale, erythrocyte sedimentation rate), and baseline DAS28-P were significantly associated with EULAR response to abatacept at 6 months. Stratified upon EULAR response, a group with good-to-moderate response had a higher baseline value and lower interval change for DAS28-P. Logistic regression analysis showed that a DAS28-P cut-off of > 0.44 was more positively associated with good-to-moderate EULAR response with abatacept treatment than naivety to biologic agents.ConclusionsThe DAS28-P could be predictive of response to abatacept. A higher baseline DAS28-P is associated with a favorable therapeutic response to abatacept.Trial registrationTrial name, Korean Post-marketing Surveillance for Orencia®. Trial registration number, NCT01583244. Registered on April 20, 2012.Electronic supplementary materialThe online version of this article (10.1007/s40271-018-0347-z) contains supplementary material, which is available to authorized users.

The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab.

IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses. Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients. Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups. RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.

Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic Literature Review

For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure. We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ). Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments. In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.

Circulating cell free DNA: a marker to predict the therapeutic response for biological DMARDs in rheumatoid arthritis.

To evaluate the correlation between circulating cell-free DNA (ccfDNA) in plasma and clinical disease activities in patients with rheumatoid arthritis (RA). The study group included 30 patients with RA who started biological disease-modifying anti-rheumatic drugs (DMARDs) therapy. The concentration of ccfDNA in plasma was measured by quantitative real-time polymerase chain reaction at baseline to 24 weeks in every 4-week period from 30 patients and 21 healthy individuals. We also evaluated the correlation between ccfDNA and the clinical activity or the therapeutic response for biological DMARDs, using the simplified disease activity index (SDAI), Disease Activity Score of 28 joints (erythrocyte sedimentation rate) and the European League Against Rheumatism (EULAR) response criteria. Synovial fluid samples of knee joints were collected from 13 patients with RA and 12 with osteoarthritis (OA) to measure ccfDNA. The concentration of ccfDNA in RA patients at baseline was higher than healthy controls (P = 0.016). After introducing biological DMARDs, ccfDNA was increased until 8 weeks from the baseline, and decreased after 12 weeks. The average of SDAI was improved in all patients enrolled. At 12 weeks after treatment, 15 patients were good responders to the EULAR response criteria, nine showed moderate response and six showed no response. ccfDNA in good responders was increased until 8 weeks, while those of moderate or no response were not (P = 0.042). In joint fluid of RA patients, ccfDNA was remarkably increased as compared to those from OA (P = 0.00011). After introducing biological DMARDs, increase of ccfDNA at 8 weeks was associated with improvement of disease activities. Compared with biomarkers reported, ccfDNA is able to predict the early therapeutic effects of biological DMARDs in RA patients.

Comparison of Disease Activity Score 28 Using C-reactive Protein and Disease Activity Score 28 Using Erythrocyte Sedimentation Rate in Assessing Activity and Treatment Response in Rheumatoid Arthritis: A Meta-analysis

Objective. We compared the Disease Activity Score 28 (DAS28) using C-reactive protein (DAS28-CRP) with DAS28 using erythrocyte sedimentation rate (DAS28-ESR) in assessing rheumatoid arthritis (RA) activity and determining European League Against Rheumatism (EULAR) response criteria. Methods. We searched the PubMed, EMBASE, and Cochrane databases and performed a meta-analysis to examine comparisons between DAS28-CRP and DAS28-ESR by RA activity and EULAR response criteria. Results. A total of ten studies were included in this meta-analysis. Significantly more patients were classified as having remission or low disease activity when using DAS28-CRP than when using DAS28-ESR (odds ratio [OR]=1.869, 95% confidence interval [CI]=1.180 to 2.959, p=0.008; OR=1.411, 95% CI=1.256 to 1.586, p=7.0×10 −8 ), whereas fewer patients were classified as having high disease activity when using DAS28-CRP than when using DAS28-ESR (OR=0.534, 95% CI=0.388 to 0.734, p=1.1×10 −4 ). More patients were classified as having good response with criteria were based on DAS28-CRP than with DAS28-ESR (OR=1.390, 95% CI=1.183 to 1.632, p=6.10×10 −5 ). Conclusion. Our meta-analysis demonstrates that DAS28-CRP underestimates disease activity and overestimates response by the EULAR response criteria compared to DAS28-ESR. (J Rheum Dis 2016;23:241-249)

Predictors of European League Against Rheumatism (EULAR) good response, DAS-28 remission and sustained responses to TNF-inhibitors in rheumatoid arthritis: a prospective study in refractory disease.

The aim of this study was to survey factors related to EULAR good response, the DAS-28 definition of remission, ACR 50 response, sustained response to tumor necrosis factor inhibitors (TNF-I) therapy in biologic naïve patients with refractory rheumatoid arthritis. This was a single center observational clinical prospective 2 years’ study, EULAR response criteria, DAS 28, HAQ and radiographic changes were recorded. Eighty patients included (64 females and 16 males, mean age was 48.4 + −17.9 years, mean disease duration 7.3 + −5.9 years). At 6 months 70% achieved EULAR good response, 51.8% achieved DAS-28 remission. Good response/sustained responses inversely correlated with baseline DAS-28 and radiographic erosions P <0.05. EULAR good response/remission by 6 months, sustained response at 2 years positively correlated with the decline in RF titers (r = 0.33, P < 0.05 & r = 0.30, P < 0.03 respectively), negatively correlated with the baseline HAQ. Regression analysis identified higher serum hemoglobin concentration, lower baseline HAQ scores, and the absence of radiographic erosions as significant predictors of good as well as sustained responses after adjustment for potential covariates. Methotrexate was associated with favorable responses and remission at 6 months (ORs = 1.13, 1.30 respectively). The study concluded that a lower baseline DAS-28 and HAQ scores, the lack of radiographic erosions favored EULAR good response and were significant predictors of sustained response to TNF-I.

Treat-to-target approach in daily clinical practice in Pakistani patients with early Rheumatoid Arthritis.

To determine the frequency of patients with early Rheumatoid Arthritis (RA) achieving disease remission and/or low disease activity after 6 months of treatment with conventional Disease Modifying Anti-Rheumatic Drugs (DMARDs) by using treat-to-target approach in routine clinical practice. Descriptive study. Division of Rheumatology, Fatima Memorial Hospital (FMH), College of Medicine and Dentistry, Lahore, from March 2011 to February 2012. Patients with early RA defined as disease duration ² 1 year were enrolled by purposive sampling, diagnosed as per American College of Rheumatology (ACR) 1987 criteria. Treat-to-target approach was defined as per European League Against Rheumatism (EULAR) 2010 guidelines for treatment of RA with conventional DMARDs. Outcome measures of remission and low disease activity were defined as per DAS 28 score criteria. Patient response to treatment was also determined by EULAR response criteria. Out of 67 patients, 50 patients completed the 6 months study period, rest were lost to follow-up. All patients were started on Methotrexate and mean weekly dose at 6 months was 18.9 ± 3.8 mg. Remission was achieved in 17 (34%) and target of low disease activity was achieved in 29 (58%) of patients. EULAR good response was seen in 28 (56%), moderate response in 21 (42%) and no response to treatment in 1 (2%). By applying treat-to-target approach in early RA, achievement of clinical remission or low disease activity with conventional DMARDs is a realistic goal in routine practice.

Brief report: rheumatoid arthritis response criteria and patient-reported improvement in arthritis activity: is an American College of Rheumatology twenty percent response meaningful to patients?

To examine the association of the American College of Rheumatology (ACR) response criteria (20% improvement [ACR20], ACR50, and ACR70) and the European League Against Rheumatism (EULAR) response criteria with patient-reported improvement in rheumatoid arthritis (RA) activity. Two hundred fifty patients with active RA were studied prospectively, before and after escalation of antirheumatic treatment. Patients were asked to report if they subjectively judged that they had experienced important improvement with treatment, and the proportion of patients who reported improvement was compared with the proportion who met the ACR20, ACR50, ACR70, and EULAR response criteria. Improvement in overall arthritis status was reported by 167 patients (66.8%), while 107 patients (42.8%) had an ACR20 response, 52 (20.8%) had an ACR50 response, 24 (9.6%) had an ACR70 response, and 136 (54.4%) had a EULAR moderate/good response. ACR20 response had a sensitivity of 0.57 and a specificity of 0.85 for clinically important improvement as judged by patients. Sensitivities of the ACR50, ACR70, and EULAR moderate/good responses were 0.30, 0.14, and 0.68, respectively, while their specificities were 0.97, 0.99, and 0.73, respectively. The ACR hybrid score with the highest sensitivity and specificity for important improvement was 19.99. Among patients with active RA, ACR20 responses are highly specific measures of improvement as judged by patients, but exclude a substantial proportion of patients who consider themselves improved. Response criteria are associated with, but not equivalent to, patient-perceived improvement.

Inhibitory effect of tacrolimus on progression of joint damage in patients with rheumatoid arthritis

To examine the inhibitory effect of tacrolimus on radiographic joint damage in patients with rheumatoid arthritis (RA). Thirty-eight patients with RA resistant or intolerant to conventional disease-modifying anti-rheumatic drugs were administered tacrolimus and analyzed retrospectively. Disease activity and clinical response were evaluated by Disease Activity Score in 28 joints and C-reactive protein (DAS28-CRP) and European League Against Rheumatism (EULAR) response criteria. The progression of joint destruction was evaluated by an estimated yearly change in modified Total Sharp Score (mTSS). Good or moderate response rate according to EULAR response criteria was seen in 63.2%, 63.2%, 73.7% and 65.8% of patients at 3, 6, 12, and 24 months, respectively. The rate of patients with low disease activity or remission reached 47.3% and 50.0% at 12 and 24 months, respectively. Progression of joint damage, evaluated as yearly change in mTSS (ΔmTSS), significantly decreased from 11.4 at baseline to 2.63 in the first year and 0.69 in the second year of tacrolimus treatment. These findings suggest tacrolimus has the potential to inhibit progression of joint damage in established RA.

Pharmacological induction of interferon type I activity following treatment with rituximab determines clinical response in rheumatoid arthritis

ObjectiveDespite the fact that rituximab depletes B cells in all treated patients with RA, not all patients show a favourable clinical response. The goal of this study was to provide...

Involvement of CX3CL1/CX3CR1 axis in etanercept therapy for patients with active rheumatoid arthritis.

ObjectiveTo examine the relationship between serum chemokine levels and patient responsiveness in rheumatoid arthritis (RA) patients to etanercept (ETN) and the influence of ETN administration on serum chemokine levels.MethodsSerum levels of the chemokines CX3CL1, CXCL8, CXCL10, and CCL3 were quantified prior to (at baseline) and after 14 weeks of treatment with ETN in 20 patients using enzyme-linked immunosorbent assay. Disease status was assessed using the Disease Activity Score (DAS28). The response to ETN was classified according to the European League Against Rheumatism (EULAR) response criteria.ResultsBy 14 weeks, ETN produced a significant overall reduction in DAS28 among the 20 patients with RA; eight patients achieved a good response, and 10 patients achieved a moderate response based on EULAR response criteria. A significant reduction in CX3CL1 was observed in the responsive group, although ETN treatment had no significant effect on the serum levels of the other three chemokines. In addition, the messenger ribonucleic acid expression of CX3CR1 in peripheral blood mononuclear cells and the cell-surface expression of CX3CR1 protein in peripheral blood CD8+CD3+ T cells were both decreased after ETN treatment.ConclusionsOur results suggest that the CX3CL1 and CX3CR1 in patients with active RA may be sensitive to antitumor necrosis factor-α therapy and confirm that CX3CL1/CX3CR1 axis plays a crucial role in the pathogenesis of RA.

Beneficial effect of 1-year etanercept treatment on the lipid profile in responding patients with rheumatoid arthritis: the ETRA study

BackgroundEffective anti-inflammatory treatment with tumour necrosis factor α (TNFα) inhibitors may have favourable effects on the lipid profile. Available evidence is derived from short-term studies, and it is not clear...

Retrospective clinical study of the efficacy of lower-dose methotrexate and infliximab therapy in patients with rheumatoid arthritis

The objective of this study is to compare the long-term outcomes of infliximab therapy with lower-dose methotrexate (MTX; < or = 4 mg per week) and with standard-dose MTX (> or = 6 mg per week) in Japanese rheumatoid arthritis (RA) patients. One hundred thirty-eight patients with refractory RA were treated with intravenous infliximab; 106 patients underwent lower-dose MTX therapy, and 32 patients underwent standard-dose MTX therapy. Treatment responses at 54 weeks or last observation carried forward (LOCF) assessed using the European League Against Rheumatism (EULAR) response criteria were compared between the two groups. Eighty-eight patients (81.1%) in the lower-dose MTX group and 27 patients (84.3%) in the standard-dose MTX therapy completed 54 weeks of infliximab treatment. A EULAR response criteria good and moderate response was seen in 70.9% in the lower-dose group and 74.1% in the standard-dose group. Good and moderate treatment responses at 54 weeks or LOCF were seen in 66.0% in the lower-dose group and 68.7% in the standard-dose group. The outcome in the lower-dose MTX group was not significantly different from that in the standard-dose group. Therapy with MTX and infliximab was effective in Japanese RA patients, regardless of MTX dosage.

Anti-TNF-α Agents Are Less Effective for the Treatment of Rheumatoid Arthritis in Current Smokers

To assess if smoking status at the time of commencing an anti-TNF-alpha agent for rheumatoid arthritis (RA) reduces the likelihood of achieving at least a moderate response on the European League Against Rheumatism (EULAR) response criteria at 3-month assessment. All patients with RA treated with their first anti-TNF-alpha agent at the Department of Rheumatology, Derby Hospital NHS Trust between April 2001 and October 2008 were included in this retrospective case control study. Information about age, gender, disease duration, body mass index, smoking status (current smoker, ex-smoker, and nonsmoker), comorbidities, oral prednisolone use, and 28 joint 4 variables disease activity score (DAS28) at the time of commencing an anti-TNF-alpha agent was recorded. Details of rheumatoid factor (RF) and past and present disease modifying antirheumatic drugs were recorded. A case control study was carried out to examine possible baseline predictors of treatment effects at the 3-month assessment. Results were available for 395 patients at 3-month assessment. According to the EULAR response criteria 42 patients failed to show at least a moderate response. After adjusting for confounders using multivariate analysis, current smoking at the time of commencing an anti-TNF-alpha agent reduced the chance of achieving at least a moderate response on the EULAR response criteria when compared with nonsmokers (aOR [95% CI] 0.20 [0.05-0.83], P = 0.03). RA patients who smoke are less likely to respond to an anti-TNF-alpha agent.

CXCL 9 and CXCL 10 as Sensitive Markers of Disease Activity in Patients with Rheumatoid Arthritis

To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response. Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6. The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05). Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.

Prospective study of methotrexate treatment for rheumatoid arthritis treated legitimately according to the government recommended 8 mg/week dose

Clinical squeal of the treatment of rheumatoid arthritis patients with methotrexate (MTX) according to the Japanese government recommended dose of 8 mg/week was evaluated prospectively. A total of 176 patients with active RA attending Konan Kakogawa Hospital and Kobe University Hospital were enrolled. Patients’ profile at the start of study was Class 2.0 ± 1.1 and X-ray stage 2.6 ± 1.0. The effects of MTX treatment were evaluated by the American College of Rheumatology (ACR) core set, disease activity score of 28 joints (DAS28), and European League Against Rheumatism (EULAR) response criteria. A modified Sharp method was used to evaluate the radiographs. The improvement in the clinical signs and symptoms of the ACR core set was maintained for a 24-month period (p < 0.05). The ACR20/50/70 and DAS28 were also improved at the 12- and 24-month assessments. However, 82 of 130 patients (63.5%) were found to be nonresponders at 24 months of MTX therapy, as evaluated by EULAR response criteria. The X-ray study showed that joint destruction progressed despite the treatment. Thus, long-term MTX treatment performed in accordance with the Japanese 8 mg/week regimen appears to be favorable in terms of the signs and symptoms of RA; however, it is clearly insufficient for and cannot halt the progression of rheumatic joint destruction.