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ID PMID Title PublicationDate abstract
26508503 Iguratimod in combination with methotrexate in active rheumatoid arthritis : Therapeutic e 2016 Oct BACKGROUND: Rheumatoid arthritis (RA) is a potentially destructive disease that may have a profound impact on patients' function and quality of life. RA therapy is still a challenge for rheumatologists; however, new antirheumatic drugs may be a treatment option for disease-modifying antirheumatic drug (DMARD)-experienced patients with active RA. OBJECTIVES: The present study is a prospective trial that aims to investigate the effects of therapy with iguratimod plus methotrexate (MTX) in comparison with iguratimod or MTX monotherapy in DMARD-experienced adult patients with active RA. METHODS: A total of 131 patients (24 men, 107 women, mean age 46.63 ± 10.61 years) with a history of being treated with traditional DMARDs were investigated. In all, 44 patients were treated with iguratimod (25 mg, twice daily, orally) plus MTX (a weekly dose of 10 mg, orally), 38 patients received iguratimod (25 mg, twice daily, orally), or 49 patients received MTX (weekly dose of 10 mg, orally) for 24 weeks. RESULTS: A therapeutic effect with iguratimod was observed between 4 and 10 weeks after treatment initiation and was effective even in patients who had a poor response to previous treatment with DMARDs. The combination of iguratimod with MTX was superior to iguratimod or MTX monotherapy. CONCLUSION: The data imply that iguratimod is a welcome addition to the small-molecule drug therapy for DMARD-experienced patients with active RA. Iguratimod (alone or in combination with MTX) is an emerging option for the treatment of DMARD-experienced adult patients with active RA who have had an inadequate response to or are intolerant of other DMARDs.
26842950 A randomised trial evaluating anakinra in early active rheumatoid arthritis. 2016 Jan OBJECTIVES: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. METHODS: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow-up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates. RESULTS: 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59). CONCLUSIONS: Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy.
27111089 Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in 2016 Sep OBJECTIVE: To assess the ability of a multi-biomarker disease activity (MBDA) test (Vectra DA) to reflect clinical measures of disease activity in patients enrolled in the AMPLE (Abatacept Versus Adalimumab Comparison in Biologic-Naive RA Subjects with Background Methotrexate) trial. METHODS: In the AMPLE trial, patients with active rheumatoid arthritis (RA) who were naive to biologic agents and had an inadequate response to methotrexate were randomized (1:1) to receive subcutaneous abatacept (125 mg every week) or subcutaneous adalimumab (40 mg every 2 weeks), with background methotrexate, for 2 years. The MBDA score was determined using serum samples collected at baseline, month 3, and years 1 and 2. The adjusted mean change from baseline in the MBDA score was compared between the abatacept and adalimumab treatment groups. Cross-tabulation was used to compare the MBDA score with the following clinical measures of disease activity: Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and Routine Assessment of Patient Index Data 3 (RAPID-3). RESULTS: In total, 318 patients were randomized to receive abatacept, and 328 were randomized to receive adalimumab; MBDA data were available for 259 and 265 patients, respectively. No association between the MBDA score and disease activity defined by the CDAI, SDAI, DAS28-CRP, or RAPID-3 in the abatacept and adalimumab treatment groups was observed. CONCLUSION: The MBDA score did not reflect clinical disease activity in patients enrolled in AMPLE and should not be used to guide decision-making in the management of RA, particularly for patients who receive abatacept or adalimumab as the first biologic agent.
27156561 Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in pat 2016 May OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we investigated the effects of tofacitinib on patient-reported outcomes (PRO) in patients with active RA. METHODS: Two, 6-month, double-blind, placebo-controlled Phase 2b studies were performed. The combination study evaluated patients with inadequate response to methotrexate who received tofacitinib 1-15 mg twice daily (BID), 20 mg once daily or placebo, on background methotrexate. In the monotherapy study, patients with inadequate response to disease-modifying anti-rheumatic drugs received tofacitinib 1-15 mg BID, adalimumab 40 mg once every other week or placebo. PROs measured were: Patient's Assessment of Arthritis Pain (PAAP), Patient's Assessment of Disease Activity, HAQ-DI, FACIT-F and SF-36. RESULTS: In the combination study (n=507), significant improvements (p<0.05) versus placebo were observed at Week 12 in PAAP (visual analogue scale) and HAQ-DI for all tofacitinib groups. In the monotherapy study (n=384), significant improvements in PAAP were observed at Week 12 for tofacitinib 5, 10 and 15 mg BID, and in HAQ-DI for tofacitinib 3, 5, 10 and 15 mg BID. Significant improvements versus placebo were seen at Week 2 in PAAP (both studies) and HAQ‑DI (monotherapy study) with tofacitinib, and were maintained throughout each study. In both studies, improvements in several domains of the SF-36 in the tofacitinib groups were observed at Weeks 12 and 24. CONCLUSIONS: In patients with active RA, tofacitinib, either in combination with methotrexate or as monotherapy, demonstrated rapid and sustained improvement in pain, physical functioning and health-related quality of life.
25703758 Treat-to-target approach in daily clinical practice in Pakistani patients with early Rheum 2015 Feb OBJECTIVE: 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. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Division of Rheumatology, Fatima Memorial Hospital (FMH), College of Medicine and Dentistry, Lahore, from March 2011 to February 2012. METHODOLOGY: 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. RESULTS: 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%). CONCLUSION: 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.
26472658 Limitations of clinical trials in chronic diseases: is the efficacy of methotrexate (MTX) 2015 Sep Clinical trials are the optimal method to establish efficacy of a drug versus placebo or another drug. Nonetheless, important limitations are seen, particularly in chronic diseases over long periods, although most are ignored. Pragmatic limitations of clinical trials include a relatively short observation period, suboptimal dosage schedules, suboptimal surrogate markers for long-term outcomes, statistically significant results which may not be clinically unimportant and vice versa. Even ideal clinical trials have intrinsic limitations, including the influence of design on results, data reported in groups which ignore individual variation, non-standard observer-dependent interpretation of a balance of efficacy and toxicity, and distortion of a "placebo effect." Limitations are seen in many clinical trials of methotrexate (MTX) in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). The first MTX clinical trial in rheumatology documented excellent efficacy in PsA, but frequent adverse events in 1964, explained by intravenous doses up to 150 kg. MTX was abandoned until the 1980s for RA, while gold salts and penicillamine were termed "remission-inducing," on the basis limitations of clinical trials. In the most recent MTX in PsA (MIPA) trial, all outcomes favoured MTX, but only patient and physician global estimates met the p<0.05 criterion. A conclusion of "no evidence for MTX improving synovitis" appears explained by insufficient statistical power, wide individual variation, no subsets, low doses, and other limitations. MTX appears less efficacious in PsA than RA, but may be underestimated in PsA, similar to historical problems in RA, resulting more from limitations of clinical trials than from limitations of MTX.
26408898 Short Communication: Lack of association between MTHFR gene polymorphisms and response to 2015 Sep Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with response to methotrexate (MTX) in certain populations of patients with rheumatoid arthritis (RA). This study aims at investigating any relationship of two single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms (C677T and A1298C) were determined in 67 RA patients (9 males and 58 females; mean age 42.87 ± 13.5 years) who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response up to 6 months. Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP, while fasting concentration of plasma homocysteine was determined using a kit method. Twenty-eight patients were found to be "good responders", while twenty-three were "poor responders". MTHFR 1298C and MTHFR 677T alleles' frequencies in "good responders" were not different from frequencies in "poor responders" (0.574 vs. 0.521; p=0.6 and 0.197 vs. 0.196; p=0.75, respectively). Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi (13.1 ± 6.7 µmol/l vs. 11.4 ± 5.3 µmol/l; p<0.001). MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients.
26200188 Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arth 2016 Jun The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading "rheumatoid arthritis" was combined with "serious infection" or "infection" or "adverse drug events" with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. These electronic searches were limited to human studies, adult studies, those published in the last 10 years (2004-14) and in the English language. Studies which involved the tumor necrosis factor-α inhibitors certolizumab pegol or golimumab were excluded. The background risk of serious infection appears to be approximately two-fold more than non-RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2-2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab.
24983407 Inhibition of radiographic joint damage in rheumatoid arthritis patients in DAS28 remissio 2015 Jan OBJECTIVE: We retrospectively investigated the inhibitory effect on radiographic joint damage (RJD) for non-biological disease-modifying antirheumatic drug (non-bioDMARD) monotherapy or methotrexate (MTX) combination therapy for rheumatoid arthritis (RA) in the disease activity score with 28 joint counts with erythrocyte sedimentation rate (DAS28) remission. METHODS: Eighty-four patients (55 cases of monotherapy, 29 cases of MTX-combination therapy) in DAS28 remission (DAS28 ≤ 2.6) were investigated from 538 RA patients newly registered between February 2007 and August 2010. The patients were analyzed for radiological assessments using the modified total Sharp score/year (mTSS/y). RESULTS: The remission rates and ΔmTSS/y for each agent using monotherapy were 7.1% and 0.17 for sulfasalazine; 11.9% and 0.49 for bucillamine (BUC); and 23.9% and 2.06 for MTX. Those using combination therapy were 6.8% and 1.39 for MTX + BUC; 23.5% and -1.64 for MTX + leflunomide; and 8.0% and 0.31 for MTX + tacrolimus. The cumulative distribution in the single and combination therapy groups showed improvement of percentages in structural remission from baseline to 1-year treatment, 34.1% to 60.9% (P < 0.05) and from 0% to 56.7%(P < 0.0001), respectively. Baseline mTSS (r = 0.67, P < 0.0001), disease duration (r = 0.40, P < 0.01), swollen joint counts (r = 0.33, P < 0.05), and anti-cyclic citrullinated peptide antibody (r = 0.31, P < 0.05) were useful predictors of RJD for non-bioDMARD monotherapy, but not for combination therapy. CONCLUSION: Satisfactory inhibition of RJD was observed in the DAS28 remission cases of monotherapy or MTX combination therapy with a non-bioDMARD.
25187185 Disease characteristics and treatment patterns in veterans with rheumatoid arthritis and c 2015 Apr OBJECTIVE: To assess disease characteristics, disease activity, and treatment patterns in rheumatoid arthritis (RA) patients with comorbid hepatitis C virus (HCV) infection. METHODS: RA patients with concomitant HCV were identified within the Veterans Affairs Rheumatoid Arthritis Registry. HCV was defined as at least 1 diagnostic code present in medical record databases. Generalized estimating equations in linear regression models compared component and composite measures of disease activity between HCV-positive and HCV-negative patients over the study period, accounting for within-subject correlations. Similar analysis of pharmacy databases evaluated medication use within each group. RESULTS: Ninety-two of 1,706 registry participants (5.1%) were identified with concomitant HCV. At enrollment, HCV-positive patients were younger (mean ± SD 61.7 ± 7.1 years versus 67.5 ± 11.2 years; P < 0.001), more often African American (35% versus 15%; P < 0.001), and smokers (48% versus 26%; P < 0.001). In unadjusted and adjusted analyses incorporating all study visits, patient-reported outcomes (pain, tender joints, and patient global scores) were higher in HCV-positive patients, contributing to higher disease activity scores. There was no difference in physician-reported outcomes (swollen joints or physician global scores). HCV-positive patients had lower C-reactive protein levels (β -0.30 [95% confidence interval (95% CI) -0.53, -0.07], P = 0.01). Over all visits, HCV-positive patients were less likely to receive methotrexate (odds ratio [OR] 0.27 [95% CI 0.17, 0.40], P < 0.001), and more likely to receive prednisone (OR 1.41 [95% CI 1.02, 1.97], P = 0.04) and anti-tumor necrosis factor α (anti-TNFα) therapies (OR 1.51 [95% CI 1.04, 2.19], P = 0.03). CONCLUSION: RA patients with concomitant HCV have higher disease activity scores, driven primarily by higher patient-reported measures. HCV-positive patients were more likely to be treated with prednisone and anti-TNFα therapies and less likely to receive methotrexate compared to HCV-negative patients.
26197989 Disseminated histoplasmosis partially mimicking a dermatomyositis in a patient with rheuma 2015 Sep Histoplasma capsulatum var. capsulatum is a dimorphic fungus endemic to America and subtropical regions. Several cases of this opportunist mycosis have been reported in immunocompromised patients. We report the case of a patient treated with methotrexate and corticosteroid therapy for rheumatoid arthritis and who presented with disseminated histoplasmosis that partially mimicked a dermatomyositis.
27339567 Frequency of metabolic syndrome in Pakistani cohort of patients with rheumatoid arthritis. 2016 Jun OBJECTIVE: To determine the frequency of metabolic syndrome in rheumatoid arthritis patients and its association with different factors i.e., age, gender, disease duration and treatment. METHODS: The cross-sectional study was conducted at Shaikh Zayed Hospital, Lahore, from July 2014 to June 2015, and comprised consecutive rheumatoid arthritis of either gender between the ages of 20 and 60 years. Frequency of metabolic syndrome was assessed by the National Education Cholesterol Programme 2004. SPSS 22 was used to compare the frequency of the syndrome among different treatment, age and gender groups. RESULTS: Of the 384 patients, 287(74.7%) were females, and 97(25.3%) were males with an overall mean age of 43.8±10.6 years (range: 20-60 years). Overall, 173(45.0%) patients were in >45years of age, and metabolic syndrome was found in 120 (31.3%). A negative association with metabolic syndrome was found when compared with treatment group of methotrexate alone and methotrexate in combination (p>0.05). CONCLUSIONS: Metabolic syndrome, an important risk factor for cardiovascular diseases, was more prevalent in rheumatoid arthritis patients.
27908307 Evolution of imaging findings, laboratory and functional parameters in rheumatoid arthriti 2017 Jan OBJECTIVES: To investigate the efficacy and safety of anti-TNF-α agent treatment compared to non-biologic DMARDs in rheumatoid arthritis patients. METHODS: 82 consecutive patients, 29 males, 53 females, aged 42-79, diagnosed with RA and suitable for anti-TNF-α treatment composed two study groups: 42 with pre-existing rheumatoid arthritis-related interstitial lung disease (RA-ILD) and 40 without RA-ILD. Respective control groups consisted of 44 patients with pre-existing RA-ILD and 44 patients without RA-ILD, treated with non-biologic DMARDs. All patients underwent chest high resolution computed tomography (HRCT), pulmonary function tests (PFTs) and peripheral blood biomarkers at baseline and after one year of treatment. RESULTS: There was a significant decrease of air trapping extent and bronchial wall thickening after treatment in RA-ILD and RA-non ILD study groups (p<0.05). This was accompanied by a statistically significant improvement of maximum mid-expiratory flow (MMEF75-25), RV and RV/TLC in both study groups (p<0.05). In the RA-ILD study group ILD extent scores remained unchanged after anti-TNF-α treatment. None of the RA-non ILD group developed new-onset ILD. In both RA-ILD and RA-non ILD control groups, HRCT findings and PFTs did not differ significantly at the one-year follow-up study. Methotrexate (MTX) regression analysis showed in both RA-ILD study and control groups a negative correlation between MTX dose and ILD extent score at one-year and between MTX dose and air trapping extent at baseline and after one year of treatment. CONCLUSIONS: Anti-TNF-α treatment, in contrast to non-biologic DMARDs, there was an improvement of small airways disease. There was no new-onset ILD or exacerbation of preexisting-ILD, especially in patients treated with anti-TNF-α agents, supporting the efficacy and favourable safety profile of this treatment in RA patients.
26995488 Evaluation of the immunogenicity of the 13-valent conjugated pneumococcal vaccine in rheum 2016 Dec OBJECTIVES: To prospectively evaluate the immunogenicity of a 13-valent conjugated pneumococcal vaccine (PCV13) in rheumatoid arthritis (RA) patients undergoing etanercept therapy. METHODS: Twenty-two RA patients treated with etanercept (ETA) in combination with methotrexate (MTX) (n=15) or monotherapy (n=7) for at least one year were included. Altogether 24 osteoarthritis patients not receiving biological or MTX therapy, treating only NSAIDs or analgesics served as controls. All subjects were vaccinated with a single dose (0.5ml) of the PCV13. Pneumococcal antibody levels at baseline, 4 and 8weeks were assessed by a VaccZyme™ Anti-PCP IgG Enzyme Immunoassay Kit. Based on recommendations of the American Academy of Allergy, Asthma & Immunology, an at least two-fold increase in antibody level, as the protective antibody response (pAR) was an indicator of responsiveness (i.e., ratio of postvaccination and prevaccination antibody levels). The antibody levels and their ratios were analysed in a variety of different ways, vaccine safety parameters (fever, infections, changes in regular antirheumatic treatments) were assessed at baseline, 4 and 8weeks after vaccination. RESULTS: Four weeks after vaccination, the anti-pneumococcal antibody levels significantly increased in both groups. At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline. Compared with postvaccination levels at 4 and 8weeks between two groups, the mean protective antibody levels were higher in control group (1st month P=0.016; 2nd month: P=0.039). Possible predictors of pAR were analysed by logistic regression model. In RA, increases of antibody levels at week 8 compared to baseline exerted a negative correlation with age, (Spearman's R=-0,431; P=0.045). There were no clinically significant side effects or reaction after administration of vaccine observed in any of these patients after the 2-month follow-up period, all patients medical condition were stable. CONCLUSIONS: In RA patients treated with ETA, vaccination with PCV13 is effective and safe, resulting in pAR one and two months after vaccination. Higher age at vaccination was identified as predictors of impaired pAR. The efficacy of vaccination may be more pronounced in younger RA patients. The vaccine is safe in RA patients on ETA.
26878896 Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biolog 2017 Mar PURPOSE: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents. METHODS: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer's II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed. RESULTS: Thirty-eight patients with a mean age of 53.00 ± 8.19 years were in group 1 and 18 patients with a mean age of 51.00 ± 9.54 years were in group 2. The mean duration of RA was 6.89 ± 7.96 years in group 1 and 5.70 ± 9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer's II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05). CONCLUSIONS: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower.
27251940 KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthriti 2016 Aug CONTEXT: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response. MATERIALS AND METHODS: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05. RESULTS: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043). DISCUSSION AND CONCLUSIONS: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.
27142240 Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid 2017 Jan OBJECTIVE: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16 mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice. METHOD: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10 mg/week or more (MTX ≥10 mg group) and <10 mg/week (MTX <10 mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria. RESULTS: The MTX ≥10 mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10 mg group (26.1%). Multivariate analysis showed that MTX ≥10 mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10 mg group compared with 52.0% in MTX <10 mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10 mg and MTX <10 mg groups (11.1% vs. 12.0%). CONCLUSIONS: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10 mg in Japanese RA patients.
27900853 An Injectable, Click-Cross-Linked Small Intestinal Submucosa Drug Depot for the Treatment 2016 Dec Here, a click-cross-linked small intestine submucosa (SIS) drug depot is described for the treatment of rheumatoid arthritis (RA). To the best of the knowledge, there have been no studies related to the intra-articular injection of methotrexate (Met)-loaded click-cross-linkable SIS (Met-loaded Cx-SIS) for RA treatment. As the key objective of this work, injectable formulations of tetrazine-modified SIS (TE-SIS) and transcyclooctene-modified SIS (TC-SIS) are employed as drug depots. Within a few seconds, the simple mixing of equal amounts of TE-SIS and TC-SIS suspensions forms a gelatinous click-cross-linked SIS (Cx-SIS) drug depot in vitro and in vivo. The formed Cx-SIS depot is maintained in the articular joint over an extended period, while SIS alone rapidly disappears. Injectable formulations of Met-loaded Cx-SIS and Met-loaded SIS are prepared and then injected into articular joints to form drug depots. Compared to animals treated with Met-loaded SIS, RA animals treated with Met-loaded Cx-SIS show effective RA repair, as well as extensive regeneration of chondrocytes and glycosaminoglycan deposits. Collectively, these results indicate that the Met-loaded Cx-SIS depot is successfully formed after intra-articular injection of click-cross-linkable SIS, and that this formulation induces long-lasting Met release and allows Met to act effectively in the articular joint, resulting in RA repair.
27452207 Evidence-based recommendations for the diagnosis and management of rheumatoid arthritis fo 2017 Sep AIM: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to joint damage, functional disability, poor quality of life and shortened life expectancy. Early diagnosis and aggressive treatment are a principal strategy to improve outcomes. To provide best practices in the diagnosis and management of patients with RA, the Thai Rheumatism Association (TRA) developed scientifically sound and clinically relevant evidence-based recommendations for general practitioners, internists, orthopedists, and physiatrists. METHODS: Thirty-seven rheumatologists from across Thailand formulated 18 clinically relevant questions: three for diagnosis, 10 for treatments, four for monitoring, and one for referral. A bibliographic team systematically reviewed the relevant literature on these topics up to December 2013. A set of recommendations was proposed based on the results of systematic reviews combined with expert opinions. Group consensus was achieved for all statements and recommendations using the nominal group technique. RESULTS: A set of recommendations was proposed. For diagnosis, either American College of Rheumatology (ACR) 1987 or ACR/European League Against Rheumatism 2010 classification criteria can be applied. For treatment, nonsteroidal anti-inflammatory drugs, glucocorticoid, and disease-modifying antirheumatic drugs, including antimalarials, methotrexate and sulfasalazine are recommended. Physiotherapy should be suggested to all patients. Tight control strategy and monitoring for efficacy and side effects of treatments, as well as indications for referral to a rheumatologist are provided. CONCLUSIONS: These evidence-based recommendations provide practical guidance for diagnosis, fundamental management and referral of patients with RA for non-rheumatologists. However, it should be incorporated with clinical judgments and decisions about care for each individual patient.
26226612 Are All Biologics the Same? Optimal Treatment Strategies for Patients With Early Rheumatoi 2015 Dec BACKGROUND: The use of biologic agents has revolutionized the treatment of rheumatoid arthritis (RA). However, there is much uncertainty about whether any agent may be preferable. PURPOSE: The aim of the study was to evaluate the comparative efficacy of biologic agents with a disease-modifying antirheumatic drug (DMARD) in RA patients without prior exposure to a DMARD, that is, DMARD naive. METHODS: MEDLINE, Cochrane, and Clinicaltrials.gov were searched from 1990 to August 2013 for randomized controlled trials comparing biologic agents in conjunction with a DMARD and DMARDs alone in DMARD (methotrexate [MTX])-naive RA patients. Information on patient characteristics, disease duration, and the American College of Rheumatology (ACR) 20/50/70/90 response rates after 52 weeks was extracted. RESULTS: Six randomized controlled trials totaling 9 study arms fulfilled the inclusion criteria. Data were analyzed by direct and indirect pairwise comparisons of 2 drugs against a common comparator. In the direct comparison, all 6 biologic therapies were associated with significantly higher likelihood of achieving an ACR20 compared with MTX alone (mean ORs, 1.43-2.99). For ACR50 and ACR70, all biologic agents except golimumab showed statistically significant mean ORs of 1.31 to 2.52 (ACR20) and 1.79 to 2.59 (ACR50). At ACR90, abatacept 10 mg/kg, adalimumab 40 mg, and rituximab 500 and 1000 mg were significantly better compared with MTX (mean ORs 1.92-2.89). The indirect comparison for ACR20 showed etanercept 50 mg significantly favored against adalimumab 40 mg (OR, 1.05-3.34), golimumab 50 mg (OR, 1.16-4.07), infliximab 3 mg/kg (OR, 1.21-3.61), and infliximab 6 mg/kg (OR, 1.02-3.06). At ACR50, etanercept 50 mg and rituximab 1000 mg showed significantly higher ORs compared with golimumab 100 mg at ORs 1.06 to 3.42 and ORs 1.07 to 3.42, respectively. No significant differences were observed in the biologic agents for indirect pairwise comparisons at ACR70 and ACR90.Lack of head-to-head clinical trial data directly comparing biologic agents makes indirect meta-analysis the only substitute. Safety and cost of these agents were not evaluated. Only a small number of trials could be evaluated because of the strict inclusion criteria required for an indirect meta-analysis. Unmeasured confounders could contribute to trial heterogeneity. The data on golimumab were difficult to reconcile with the other trials because of methodological differences. CONCLUSIONS: Overall, biological agents in conjunction with a DMARD performed similarly in the settings evaluated. However, there were some statistically significant differences. Etanercept 50 mg appears superior to adalimumab 40 mg, golimumab 50 mg, and infliximab 3 and 6 mg/kg at ACR20. Rituximab 1000 mg and etanercept 50 mg appeared superior to golimumab 100 mg at ACR50 in DMARD-naive patients. No agent was superior to all others at each ACR level.