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ID PMID Title PublicationDate abstract
29657870 Is the serum oxytocin level altered by treatment in rheumatoid arthritis patients complica 2018 Mar OBJECTIVE: The objective of this study was to investigate the factors associated with depression, including serum oxytocin (OXT) levels, disease activity, activities of daily living (ADL), and quality of life (QOL), and their effects on rheumatoid arthritis (RA). METHODS: This study included 42 RA patients who received treatment with a biological agent. We measured the following variables before and after 6 months of treatment: baseline characteristics, including age, sex, disease duration, smoking, and body mass index (BMI); prednisolone and methotrexate dose; serum level of matrix metalloproteinase-3 (MMP-3); erythrocyte sedimentation rate (ESR); and C-reactive protein (CRP) level. The disease activity of RA was assessed using the Simplified Disease Activity Index (SDAI); depression was assessed using the Hamilton Depression Rating Scale (HAM-D); ADL was assessed using the Health Assessment Questionnaire; and QOL was assessed using the Short Form (SF)-36. Serum OXT levels were determined using enzyme-linked immunosorbent assay. RESULTS: The HAM-D score significantly correlated with the SDAI, and the mental component summary (MCS) score of SF-36. However, the serum OXT levels did not correlate with the HAM-D score. Regression analysis using the HAM-D score as the objective variable identified female sex, smoking, BMI, and all the three component scores of SF-36, but not serum OXT levels, as significant factors. Comparisons between before and after treatment showed that the HAM-D score improved from 5 to 1.5; however, the serum OXT levels did not change. CONCLUSION: The variables of female sex, smoking, BMI, and QOL correlated with depression complicated with RA. However, serum OXT levels did not correlate directly.
29618976 The Efficacy and Safety of Mainstream Medications for Patients With cDMARD-Naïve Rheumato 2018 Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA. Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals (CrI). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that. Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments concerning should be introduced with caution.
29417430 Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib 2018 Jun INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy. METHODS: Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC. RESULTS: By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation. CONCLUSIONS: Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX. FUNDING: Pfizer Inc. TRIAL REGISTRATION: Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].
30293218 Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor 2018 Dec INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA. METHODS: TCZ-naïve patients from the Corrona RA registry with prior exposure to ≥ 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI ≤ 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose (≤ 10 mg; > 10 to ≤ 15 mg; > 15 to ≤ 20 mg; > 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups. CONCLUSIONS: In this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC. Plain language summary available for this article.
31070537 Mangosteen ethanol extract alleviated the severity of collagen-induced arthritis in rats a 2018 Dec CONTEXT: Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases. OBJECTIVE: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo. MATERIALS AND METHODS: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry. RESULTS: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p < 0.05) and notably alleviated synovial hyperplasia and cartilage degradation in joints. Different from methotrexate, MAN significantly augmented CD25(+) cells distribution (from 2.72 to 3.35%) and IL-10 secretion (from 202.4 to 241.2 pg/mL) in CIA rat blood. Meanwhile, MAN induced a greater IL-17 decrease and a FOXP3 increase in immune organs than MTX. Reduced TLR4 and IL-17 expression and elevated FOXP3 expression in joints also occurred under MAN treatment. CONCLUSIONS: MAN protected joints from destruction in CIA rats and exerted synergistic effects with methotrexate by improving immune microenvironment. The combination regimen could bring additional benefits to rheumatoid arthritis patients.
29657830 Conversion to seronegative status after abatacept treatment in patients with early and poo 2018 OBJECTIVE: To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response. METHODS: Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months. Autoantibody titres were determined by ELISA at baseline and months 6 and 12 (double-blind phase). Conversion to seronegative status and its association with clinical response were assessed at months 6 and 12. RESULTS: Abatacept plus MTX was associated with a greater decrease in ACPA (but not RF) titres and higher rates of both ACPA and RF conversion to seronegative status versus MTX alone. More patients converting to ACPA seronegative status receiving abatacept plus MTX achieved remission according to Disease Activity Score in 28 joints (C-reactive protein) or Clinical Disease Activity Index than patients who remained ACPA seropositive. Patients who converted to ACPA seronegative status treated with abatacept plus MTX had a greater probability of achieving sustained remission and less radiographic progression than MTX alone or patients who remained ACPA seropositive (either treatment). CONCLUSIONS: Treatment with abatacept plus MTX was more likely to induce conversion to ACPA/RF seronegative status in patients with early, erosive RA. Conversion to ACPA seronegative status was associated with better clinical and radiographic outcomes. TRIAL REGISTRATION NUMBER: NCT00122382.
29987858 Methotrexate-associated lymphoproliferative disorders with angioimmunoblastic T-cell lymph 2018 Jul 10 Although gamma heavy chain disease (γ-HCD) lesions occasionally morphologically resemble angioimmunoblastic T-cell lymphoma (AITL), no association has been described in detail due to the rarity of the disease. In this report, we present a rare manifestation of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) with AITL-like features accompanied by γ-HCD in a 75-year-old man with rheumatoid arthritis (RA). A biopsy specimen was evaluated using immunohistochemistry, clonal analyses of immunoglobulin V(H) and T-cell receptor γ gene rearrangements by polymerase chain reaction, and Sanger sequencing for confirmation of the structure of deleted γ-HCD clones. The histological features characterized by proliferation of CD4- and PD-1-positive medium-sized T cells and arborizing high endothelial venules together with numbers of small lymphocytes, eosinophils, plasma cells, and histiocytes in the background mimicked those of AITL, but did not completely fulfill the diagnostic criteria. Clonal analysis demonstrated that the specimen contained multiple LPDs of both B-cell and T-cell lineages. Sequence analysis confirmed the co-existence of a clone responsible for production of the abnormal heavy chain. This report provides new insights into the pathology of γ-HCD. Multiple host-derived factors (e.g., RA and/or use of MTX) may be responsible for the occurrence of LPDs of multiple lineages within a single lymph node.
28758587 Atypical form of Adult-onset Still's Disease with Distal Interphalangeal Joints Involvemen 2018 BACKGROUND: A distal interphalangeal (DIP) joint involvement in the adult-onset Still's disease (AOSD) has been described in some publications but is rarely reported to be severe. We report severe DIP joints damages in a young patient with AOSD. CASE REPORT: A 22 years old patient presented to our department complaining of inflammatory joints pain associated with prolonged fever and cutaneous rash. Physical examination identified polyarthritis and hepatosplenomegaly but no lymphadenopathies. After an extensive screening for neoplastic, infectious or hematologic diseases, the patient was finally diagnosed with AOSD. Treatment based on corticosteroids was then initiated with a good response on systemic signs. However, the patient continued to have recurrent arthritis affecting wrists and proximal interphalangeal joints. A Few years later, he developed a severe and disabling DIP arthritis with signs of joint destruction on conventional radiographs and MRI. Despite the initiation of methotrexate with optimal dosage, the patient continued to have polyarticular flares. The combination of methotrexate and sulfasalazine was responsible for drug-induced hepatotoxicity and this treatment was stopped. Anti-TNFα treatment was then indicated as general signs improved but severe joints damage persisted. Unfortunately, and due to healthcare system considerations, the patient was not able to benefit from TNFα inhibitors, and remained on methotrexate treatment only. CONCULSION: The distal destructive arthritis during AOSD is rare and controversial. Our patient had a severe form with resistance to conventional therapies.
29992108 Anti-rheumatoid activity of ethanolic extract of Sesamum indicum seed extract in Freund's 2018 Jul Sesamum indicum, one of the first recorded plants used for its seeds, is reported to have analgesic, antioxidant, anticancer, anti-obesity as well as hepato and nephro protective activities. The current study evaluated the effects of two doses (400 and 800 mg/kg) of ethanolic extract of S. indicum seeds in Freund's complete adjuvant induced arthritis in rats in comparison with diclofenac and methotrexate by the changes produced in body weight, body temperature, paw volume and spontaneous activity, hemoglobin, erythrocyte sedimentation rate, total white blood cells, red blood cells, Interleukin-6 and Tumor necrosis factor-α as well as joint changes in X-ray and histological changes in joint tissue. Unlike the untreated group, the groups treated with S. indicum showed significant decrease in paw volume, body weight, white blood cell count, erythrocyte sedimentation rate, Interleukin-6 and Tumor necrosis factor-α and an increase in body weight, spontaneous activity, hemoglobin level, and red blood cell count. Histopathological examination showed gross reduction in synovial inflammation and cartilage damage. X-ray revealed significant improvement in joint space. The effect of ethanolic extract of S. indicum was found to be equivalent to methotrexate and greater than diclofenac.
29732036 Effect of long-term low dose prednisolone administration on bone mineral density: Relating 2018 Spring BACKGROUND: Long-term treatment of rheumatoid arthritis (RA) with prednisolone (PRED) is associated with bone mineral density (BMD) loss. This study aimed to determine the status of BMD in non-compliant women who used PRED alone for RA. METHODS: Non-adherent RA taking < 7.5 mg daily PRED without DMARDs for > 6 months, and RA patients taking methotrexate +PRED (RA control) were compared with age-matched non-RA controls. BMD was measured by dual energy x-ray absorptiometry (DXA) method and osteoporosis (OP) was diagnosed by WHO criteria. Influence of PRED on RA bone mass, and the risk of OP in RA was assessed by comparing PRED users RA and RA control,versus non-RA controls. RESULTS: Sixty-four PRED user RA, 39 RA controls and 111 non RA-controls, with respective mean (±SD) age of 52±11; 8, 51±11; and 52±7.5 years (P=0.91) were studied. Median duration of treatment in PRED users and RA control was 2.5 and 4 years, respectively. BMD g/cm(2) at the femoral neck (FN-BMD) and lumber spine (LS-BMD) in PRED users and RA control was significantly lower than non-RA control (P=0.001). The prevalence of OP at either FN or LS in both RA groups was significantly higher than controls (P=0.001). In PRED users, the risk of OP increased by OR=4.9, P=0.001) and in RA controls by OR=1.7 (P=0.20). The risk of OP in PRED user RA was 2.89 times (P=0.014) greater than RA controls. CONCLUSIONS: These findings indicate significantly lower BMD, and higher prevalence of osteoporosis in non-compliant women with RA taking low-dose PRED alone for a median period of 2.5 years, as compared with patients taking standard treatment comprising methotrexate +PRED.
29479473 Response to baricitinib therapy in patients with rheumatoid arthritis with inadequate resp 2018 OBJECTIVE: We analysed the effects of baseline characteristics on the safety and efficacy of baricitinib in patients with rheumatoid arthritis (RA) with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) from two phase III trials. METHODS: In RA-BEAM (NCT01710358), patients with inadequate response to methotrexate were randomised to placebo, baricitinib 4 mg or adalimumab 40 mg. RA-BUILD (NCT01721057) patients had inadequate response to ≥1 csDMARDs and were randomised to either placebo or once-daily baricitinib (2 or 4 mg). Both study populations were naïve to biologic DMARDs (bDMARDs). Primary end point for both studies was American College of Rheumatology 20% improvement (ACR20) response at week 12. Pooled data from the two trials were analysed post hoc based on select subgroups defined by age, previous csDMARD use, baseline RA disease activity, etc, with assessment of clinical and safety outcomes at week 12 and radiographic outcomes at week 24 for the baricitinib 4 mg and placebo-treated patients. RESULTS: Efficacy was observed with baricitinib 4 mg treatment irrespective of patient demographics and baseline disease characteristics. ORs primarily favoured baricitinib over placebo in the ACR20 response. In other outcomes such as Disease Activity Score for 28 joints based on high-sensitivity C reactive protein levels, Simplified Disease Activity Index score ≤11 and radiographic progression, baricitinib 4 mg showed better responses than placebo regardless of baseline characteristics. Safety events were more common in patients over 65 years, but similar between baricitinib 4 mg and placebo patients. CONCLUSION: Baseline characteristics did not substantially affect clinical response to baricitinib 4 mg in patients with RA with inadequate response to csDMARDs.
30197693 Evaluation of Effect of Low-Dose Methotrexate on Osseointegration of Implants: A Biomechan 2018 BACKGROUND: Methotrexate (MTX) is an immunosuppressive drug, widely used in inflammatory disturbances including rheumatoid arthritis. However, there is no consensus regarding the effect of MTX on implant osseointegration. OBJECTIVE: The purpose of this experimental study was to investigate the effect of low dose MTX on Bone-Implant Contact (BIC) of dogs. METHODS: Six mandibular premolar teeth (bilateral) of 8 mature dogs were extracted. After 3 months of healing, 6 implants (bone level, resorbable blast media surface) were inserted into the mandible of each dog (3 in each side). Dogs were randomly divided into a study group (receiving 2.5 mg/week MTX orally, 3 times per week for 4 weeks) and a control group each containing 4 dogs. In the 1(st) week, postoperative BIC was evaluated in 4 dogs, two from each group. In the 4(th) week, reverse torque and BIC were evaluated in the remaining 4 dogs. Data were analyzed with two-way ANOVA test for 95% confidence interval. RESULTS: The reverse torque test of the 4(th) week, showed a satisfying osseointegration. Histopathologic evaluation revealed that the BIC was significantly higher in the control group in comparison to the MTX group in the 1(st) and 4(th) week. In addition, the BIC of both groups were significantly increased in the 4(th) week in comparison to the 1(st) week in both groups. CONCLUSION: MTX has the potential to interfere with osseointegration process.
29358919 The Calcium-Induced Regulation in the Molecular and Transcriptional Circuitry of Human Inf 2017 Rheumatoid arthritis synovial fibroblasts (RASFs) are fundamental effector cells in RA driving the joint inflammation and deformities. Celastrol is a natural compound that exhibits a potent anti-arthritic effect promoting endoplasmic reticulum (ER) stress mediated by intracellular calcium (Ca(2+)) mobilization. Ca(2+) is a second messenger regulating a variety of cellular processes. We hypothesized that the compound, celastrol, affecting cytosolic Ca(2+) mobilization could serve as a novel strategy to combat RA. To address this issue, celastrol was used as a molecular tool to assay the inflammatory gene expression profile regulated by Ca(2+). We confirmed that celastrol treatment mobilized cytosolic Ca(2+) in patient-derived RASFs. It was found that 23 genes out of 370 were manipulated by Ca(2+) mobilization using an inflammatory and autoimmunity PCR array following independent quantitative PCR validation. Most of the identified genes were downregulated and categorized into five groups corresponding to their cellular responses participating in RA pathogenesis. Accordingly, a signaling network map demonstrating the possible molecular circuitry connecting the functions of the products of these genes was generated based on literature review. In addition, a bioinformatics analysis revealed that celastrol-induced Ca(2+) mobilization gene expression profile showed a novel mode of action compared with three FDA-approved rheumatic drugs (methotrexate, rituximab and tocilizumab). To the best of our knowledge, this is a pioneer work charting the Ca(2+) signaling network on the regulation of RA-associated inflammatory gene expression.
30546311 Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Me 2018 Objective: Analysis of the relationship between single nucleotide polymorphisms (SNPs) and outcomes of methotrexate (MTX) therapy for rheumatoid arthritis (RA) in China. Materials and Methods: TYMS 28 bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) enzyme proteins may be related to the outcomes of MTX therapy, according to our previous meta-analysis. A total of 162 patients with RA were included in our study. SNPs were evaluated using polymerase chain reaction (PCR). Disease Activity Score 28 (DAS28) was used to evaluate the clinical response, and adverse drug reactions (ADRs) were collected after physical examinations of the patients. Results: The MTHFR 677C>T gene showed a relationship with the ADRs of MTX in the Recessive model [TT vs. (CC+CT)] (p = 0.04, OR = 2.20, 95% CI: 1.01, 4.77). In the Codominant model [CT vs. (CC+TT)], the MTHFR 677C>T gene also showed a trend of association with ADRs (p = 0.08, OR = 0.52, 95% CI: 0.25, 1.08). No significant difference was found between TYMS, MTHFR, ATIC, MTR, and MTRR gene polymorphisms and the RA response or ADRs related to MTX in our study. Conclusion: Our results showed that the MTHFR [677C>T (rs1801133)] TT genotype is associated with ADRs to MTX in Chinese RA patients. Other SNPs, including TYMS 28bp VNTR (rs34743033), MTHFR [677C>T (rs1801133) and 1298A>C (rs1801131)], ATIC 347C>G (rs2372536), MTR A2756G (rs1805087), and MTRR 66A>G (rs1801394) gene polymorphisms, were not associated with MTX treatment outcomes. Further studies are required to validate these findings.
29949132 Tofacitinib, an Oral Janus Kinase Inhibitor: Pooled Efficacy and Safety Analyses in an Aus 2018 Dec INTRODUCTION: In Australia, there is an unmet need for improved treatments for rheumatoid arthritis (RA). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. To provide an overview of key study outcomes for tofacitinib in Australian patients, we analyzed the efficacy and safety of tofacitinib in the Australian subpopulation of global RA phase III and long-term extension (LTE) studies. METHODS: Data were pooled from the Australian subpopulation of four phase III studies and one LTE study (database not locked at cut-off date: January 2016). Patients in the phase III studies received tofacitinib 5 or 10 mg twice daily (BID), placebo (advancing to tofacitinib at months 3 or 6), or adalimumab, with background methotrexate or conventional synthetic disease-modifying antirheumatic drugs. Patients in the LTE study received tofacitinib 5 or 10 mg BID. Efficacy endpoints were American College of Rheumatology (ACR) 20/50/70 response rates, and change from baseline in the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Safety endpoints included incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs. AEs of special interest and laboratory parameters were analyzed in the LTE study. RESULTS: Across phase III studies (N = 100), ACR response rates and improvements in DAS28-4(ESR) and HAQ-DI scores were numerically greater with tofacitinib vs. placebo at month 3, and increased until month 12. The results were sustained in the LTE study (N = 99) after 60 months' observation. In general, the efficacy and safety profiles of tofacitinib were similar to those of the global RA population. CONCLUSIONS: In Australian patients with RA, tofacitinib therapy demonstrated sustained efficacy and consistent safety over ≥ 60 months' treatment. FUNDING: Pfizer Inc. TRIAL REGISTRATION NUMBERS (ALL CLINICALTRIALS.GOV): NCT00960440; NCT00847613; NCT00856544; NCT00853385; NCT00413699.
29350072 A new polyoxygenated abietane diterpenoid from the rattans of Bauhinia championii (Benth.) 2018 Nov A new polyoxygenated abietane diterpenoid, bauchampine A (1), together with seven known compounds (2-8), were isolated from the rattans of Bauhinia championii (Benth.) Benth. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with the data reported in the literature. New compound 1 was evaluated for its anti-rheumatoid arthritis activity via examining its anti-proliferative effect on synoviocytes in vitro. Compound 1 exhibited inhibitory effect on the proliferation of synoviocytes with IC(50) value comparable to that of methotrexate.
30618762 Integrating Network Pharmacology and Metabolomics Study on Anti-rheumatic Mechanisms and A 2018 Qing-Luo-Yin (QLY) is a traditional Chinese medicine (TCM) formula used to treat Hot Syndrome-related rheumatoid arthritis (RA). Previously, we uncovered partial mechanisms involved in the therapeutic actions of QLY on RA. In this study, we further elucidated its anti-rheumatic mechanisms and investigated its possible interactions with methotrexate (MTX) in vivo using an integrating strategy coupled with network pharmacology and metabolomics techniques. Chemical composition of QLY was characterized by HPLC analysis. Collagen induced arthritis (CIA) was developed in male SD rats. The CIA rats were then assigned into different groups, and received QLY, MTX or QLY+MTX treatments according to the pre-arrangement. Therapeutic effects of QLY and its possible interactions with MTX in vivo were evaluated by clinical parameters, digital radiography assessment, histological/immunohistochemical examination, and serological biomarkers. Mechanisms underlying these actions were deciphered with network pharmacology methods, and further validated by metabolomics clues based on UPLC-Q-TOF/MS analysis of urines. Experimental evidences demonstrated that QLY notably alleviated the severity of CIA and protected joints from destruction. Re-balanced levels of hemoglobin and alanine transaminase in serum indicated reduced MTX-induced hepatic injury and myelosuppression under the co-treatment of QLY. Network-based target prediction found dozens of RA related proteins as potential targets of QLY. Upon the further biological function enrichment analysis, we found that a large amount of them were involved in nucleotide metabolism and immune functions. Metabolomics analysis showed that QLY restored amino acids, fatty acids, and energy metabolisms in CIA rats, which solidly supported its therapeutic effects on CIA. Consistently to findings from network pharmacology analysis, metabolomics study also found altered purine, pyrimidine, and pentose phosphate metabolisms in CIA rats receiving QLY treatment. All these clues suggested that inhibition on nucleic acid synthesis was essential to the immunosuppressive activity of QLY in vivo, and could contribute great importance to its therapeutic effects on CIA. Additionally, QLY induced significant antifolate resistance in rats, which would prevent folate from depletion during long-term MTX treatment, and should account for reduced side effects in combination regimen with MTX and QLY.
29361202 Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review. 2018 Oct OBJECTIVE: Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis. METHODS: A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov. RESULTS: Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non-controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001). CONCLUSION: The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo-controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.
30886957 Methotrexate therapy impacts on red cell distribution width and its predictive value for c 2018 BACKGROUND: Methotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation. We thus questioned whether RDW levels and subsequently its diagnostic utility in RA subjects, as reported before, are influenced by ongoing MTX therapy.We assessed the impact of disease modifying drug (DMARD) treatment, especially MTX, on RDW and evaluated their influence on the predictive value of RDW for cardiovascular (CV) events in patients with rheumatoid arthritis (RA). As far as we know, this is the first study evaluating the influence of MTX on RDW. METHODS: Medical treatment, disease activity, laboratory parameters and history of CV events were retrospectively analysed in 385 RA patients at disease onset and at last follow up at our clinic. Additionally, in patients with CV event, data were recorded at last follow up prior the CV event. RESULTS: Disease parameters and laboratory findings associated with a serious vascular event were older age (p < 0,001), longer disease duration (p = 0,002) and a higher RDW at diagnosis (p = 0,025). No differences in RDW levels became evident with any other treatment regimen beside MTX. MTX treated patients had significantly higher RDW compared to subjects without this drug (p < 0,001). In RA patients without MTX treatment, we found RDW level significantly different between those with versus without a CV event, whereas this difference disappeared in subjects receiving MTX. CONCLUSION: MTX impacts on RDW and might therefor reduce its prognostic value for CV events in patients taking MTX, whereas an increased RDW at diagnosis remains an early risk predictor for myocardial infarction and stroke in RA patients.
29225245 Oral Methotrexate-related Lymphoproliferative Disease Presenting with Severe Osteonecrosis 2018 Feb 15 Long-term methotrexate (MTX) treatment can cause MTX-related lymphoproliferative disorder (MTX-LPD). We experienced a case of MTX-LPD that was associated with severe osteonecrosis of the jaw mimicking medication-related osteonecrosis of the jaw. The patient was an 81-year-old woman with rheumatoid arthritis (RA) who was treated with MTX and bisphosphonate. After 7 years, she was referred to our department for the assessment of giant ulcer and exposure of the alveolar bone of the left maxilla. Histopathological and immunological analyses confirmed a diagnosis of MTX-LPD. At seven months after the cessation of MTX treatment, the ulcerative and necrotic lesions had markedly decreased in size. A 1-year follow-up examination showed no evidence of recurrence and good RA control.