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30356765 Treatment of Rheumatoid Arthritis Using Combination of Methotrexate and Tripterygium Glyco 2018 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by chronic destructive synovitis and is associated with progressive disability, systemic difficulties, premature death, and socioeconomic costs. Early intervention with disease-modifying antirheumatic drugs (DMARDs) like methotrexate (MTX) and its combination regimen would provide obvious benefits to patients, healthcare systems and society. MTX and tripterygium glycosides tablets (TGT(S)) are most frequently prescribed medicines for RA, and the combination of them occurs frequently in anti-RA prescriptions. While the underlying combination mechanisms and the affected variation of drug blood level remain unclear. According to the American College of Rheumatology criteria for improvement, clinical evaluation following three treatment groups (i.e., MTX and TGT(S) mono- and combined groups) were carried out at baseline and at the end of 12 weeks in a randomized controlled clinical trial. To monitor the affected variation of drug blood level and perturbation of metabolites caused by MTX plus TGT(S) combined to treat active RA, the collected plasma samples were analyzed using RRLC-QqQ-MS and UHPLC-QE Orbitrap HRMS instruments. As a result, 39 metabolites including 7 MTX-related metabolites, 13 TGT(S)-related migratory ingredients and 19 characteristic endogenous metabolites, were quantitatively determined in plasma samples of RA patients after oral administration. The potential mechanism of MTX and TGT(S) combination were preliminarily elucidated on the aspect of clinical biochemical test indicators integrated with quantitative plasma pharmacochemistry and the pseudotargeted metabolomics.
29540195 Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced 2018 Mar 14 BACKGROUND: Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. METHODS: CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. RESULTS: Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. CONCLUSIONS: Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.
30697252 Efficacy and safety of various anti-rheumatic treatments for patients with rheumatoid arth 2019 Jan INTRODUCTION: Biologics and traditional disease-modifying anti-rheumatic drugs (DMARDs) are generally used in treating patients with rheumatoid arthritis (RA). Previous studies have presented abundant data and information about the efficacy of such treatments, but the results were incomplete and inconclusive. This network meta-analysis was conducted to compare and assess the efficacy and safety of 15 therapies employing biologics and DMARDs for RA patients. MATERIAL AND METHODS: Six outcomes (American College of Rheumatology 20% response rate (ACR20), ACR50, ACR70, remission, adverse events (AEs) and serious adverse events (SAEs)) were used to evaluate the efficacy and safety of different treatments. The node-splitting method was used to assess the inconsistency, and the rank probabilities of the therapies were estimated by surface under the cumulative ranking curve. Besides, Jadad scale was used to evaluate the methodological quality of eligible studies. RESULTS: A total of 67 randomized controlled trials with 20,898 patients met the inclusion criteria. Most of the therapies presented better performance than conventional DMARDs (cDMARDs) and placebo in ACR20, ACR50 and ACR70. Conversely, the safety of cDMARDs and placebo seemed to be superior in AEs and SAEs. Also, tocilizumab (TCZ) and TCZ + methotrexate (MTX) showed better remission in pain compared to other treatments. Overall, certolizumab pegol (CZP) + MTX and TCZ + MTX had higher probability than the other treatments in efficacy outcomes. CONCLUSIONS: We recommend CZP + MTX as the optimal drug therapy because it has the highest ranking in efficacy outcomes and relatively low risk of adverse events. TCZ + MTX is recommended as an alternative. Abatacept (ABT) and cDMARDs are not recommended due to their low efficacy.
29480357 Maintenance of Remission with Etanercept-DMARD Combination Therapy Compared with DMARDs Al 2018 Jun INTRODUCTION: To compare etanercept (ETN) and placebo (PBO) for maintaining low disease activity (LDA) achieved with ETN in patients with rheumatoid arthritis (RA) from Africa and the Middle East. METHODS: In this subset analysis of the Treat-to-Target trial (ClinicalTrials.gov identifier NCT01981473), 53 adult patients with moderate-to-severe RA nonresponsive to methotrexate were treated with 50 mg ETN/week for 24 weeks (Period 1). Patients achieving LDA were randomized to continue ETN treatment or switched to PBO for an additional 28 weeks (Period 2). The proportion of patients maintaining LDA or remission in each arm at the end of Period 2 was determined. Additional efficacy and patient-reported outcomes (PROs) were also evaluated. RESULTS: During Period 1, 51 patients achieved LDA according to the disease activity score-28 joints-erythrocyte sedimentation rate (DAS28-ESR LDA) and 30 achieved remission. At week 52, nine of 22 and eight of 29 in the ETN and PBO groups, respectively, remained in DAS28-ESR LDA without experiencing a flare. Additionally, six of 14 and five of 16 in the ETN and PBO groups, respectively, remained in remission. Among patients experiencing a flare during Period 2, 13 of 22 and 21 of 29 received ETN or PBO, respectively. The median time to flare was 193 and 87 days in the ETN and PBO groups, respectively. At week 52, consistently more patients in the ETN group than in the PBO group achieved predetermined efficacy and PRO endpoints. CONCLUSIONS: These data suggest continuing ETN maintenance therapy is beneficial to patients after they have achieved their treatment target. However, this subset analysis is limited by the small patient population and must be interpreted with caution. FUNDING: Pfizer. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT0198147.
30122937 Azilsartan improves the effects of etanercept in patients with active rheumatoid arthritis 2018 BACKGROUND AND AIM: Much evidence has emerged documenting the involvement of the renin-angiotensin system (RAS) in inflammatory processes. The objective of this study was to evaluate the effects of blocking RAS with azilsartan (Azil) on the clinical efficacy of etanercept (Etan) in patients with active rheumatoid arthritis (RA). PATIENTS AND METHODS: Forty-two patients diagnosed with active RA and poorly responding to methotrexate were enrolled in this pilot clinical study. They were randomly allocated into two groups, and treated with either Etan (50 mg/week) and placebo or the same dose of Etan with Azil (20 mg/day) for 90 days. The clinical outcome was evaluated using the Disease Activity Score-28 joint (DAS-28), simplified disease activity index (SDAI), clinical disease activity index (CDAI) and the health assessment questionnaire disease index (HAQ-DI). Blood samples were obtained for the assessment of C-reactive protein and erythrocyte sedimentation rate at baseline and after 90 days. RESULTS: The markers of pain and disease activity, C-reactive protein and erythrocyte sedimentation rate were significantly improved when Azil was used, as an adjuvant with Etan, compared with the use of Etan and placebo. CONCLUSION: Blocking RAS with azilsartan may improve the effects of etanercept on the clinical markers of pain and disease severity of patients with active RA not responding to methotrexate.
29422864 Clinical Pharmacogenetic Models of Treatment Response to Methotrexate Monotherapy in Slove 2018 Objectives: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but nevertheless 30% of patients experience MTX inefficacy. Our aim was to develop a clinical pharmacogenetic model to predict which RA patients will not respond to MTX monotherapy. We also assessed whether this model can be generalized to other populations by validating it on a group of Serbian RA patients. Methods: In 110 RA Slovenian patients, data on clinical factors and 34 polymorphisms in MTX pathway were analyzed by Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression to select variables associated with the disease activity as measured by Disease Activity Score (DAS28) score after 6 months of MTX monotherapy. A clinical pharmacogenetic index was constructed from penalized regression coefficients with absolute value above 0.05. This index was cross-validated and also independently validated on 133 Serbian RA patients. Results: A clinical pharmacogenetic index for prediction of DAS28 after 6 months of MTX monotherapy in Slovenian RA patients consisted of DAS28 score at diagnosis, presence of erosions, MTX dose, Solute Carrier Family 19 Member 1 (SLC19A1) rs1051266, Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) rs2306283, Thymidylate Synthase (TYMS), and Adenosine Monophosphate Deaminase 1 (AMPD1) rs17602729. It correctly classified 69% of Slovenian patients as responders or nonresponders and explained 30% of variability in DAS28 after 6 months of MTX monotherapy. Testing for validity in another population showed that it classified correctly only 22.5% of Serbian RA patients. Conclusions: We developed a clinical pharmacogenetic model for DAS28 after 6 months of MTX monotherapy in Slovenian RA patients by combining clinical and genetic variables. The clinical pharmacogenetic index developed for Slovenian patients did not perform well on Serbian patients, presumably due to the differences in patients' characteristics and clinical management between the two groups.
29955385 Clinical and radiographic course of early undifferentiated arthritis under treatment is no 2018 OBJECTIVE: To analyse whether early arthritis patients who do not fulfil the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 classification criteria for rheumatoid arthritis (RA) have a different course of the disease dependent on whether they can or cannot be classified as RA because of radiographic disease (EULAR task force) at diagnosis. METHODS: For this observational study within the Swiss RA cohort SCQM, we included patients with early undifferentiated arthritis (disease duration ≤1 year), who had not received any previous disease-modifying antirheumatic drugs (DMARDs). 2010 ACR/EULAR criteria negative patients were separated into two groups (radiographic vs non-radiographic arthritis) depending on whether or not they had radiographic changes defined as erosive disease by a EULAR task force (≥3 joints with erosions). The primary outcome measure was the radiographic progression detected employing the Ratingen erosion score. Health Assessment Questionnaire (HAQ) and DAS-28 were used as secondary outcome measures. The average observation period was 4 years. RESULTS: A total of 592 patients were analysed. 240 were not classifiable as RA by application of the 2010 ACR/EULAR criteria at baseline. In 57 patients, radiographs at the first visit were not available. 133 patients had radiographic arthritis and 50 non-radiographic arthritis. Treatment was initiated in all patients with DMARDs, mostly methotrexate. No differences in DAS-28 and HAQ scores were found during follow-up. The average erosion scores were higher among patients with initially radiographic arthritis throughout the study. The progression of erosion scores over time, however, was higher in patients with initially non-radiographic arthritis with less subsequent radiological progression (3.3 erosions/year vs 0.4, respectively, p<0.0001). CONCLUSIONS: The clinical and radiographic course of early undifferentiated arthritis under treatment was not dependent on the presence of erosions in three or more joints (ie, the definition of radiographic disease by the EULAR task force) at diagnosis in our cohort.
30206553 The use of biologic therapies in uveitis. 2018 Apr PURPOSE: Non-infectious uveitis has been long controlled with the use of corticosteroids with many side effects and poor control in some cases. The purpose of this paper was to assess the different biologic agents (in this case infliximab and adalimumab) and to compare their efficacy in the treatment of uveitis. RESULTS: Adalimumab has been proven very successful in replacing or aiding corticosteroid therapy in different autoimmune mediated uveitis (Juvenile Idiopathic Arthritis, Rheumatoid arthritis, sarcoidosis) whereas infliximab has been used intravenously and recently intravitreally with very promising results in controlling Behcet's related uveitis. CONCLUSION: Biologic Response Modifiers represent the future of therapy in immune-mediated uveitis. Abbreviations AU = Anterior Uveitis, BCVA = Best Corrected Visual Acuity, BRM = Biologic Response Modifiers, CME = Cystoid Macular Oedema, CPR = C Protein Reactive, ESR = Erythrocyte Sediment Rate, HSV = Herpes Simplex Virus, ICAM = Intercellular Adhesion Molecules, IMT = Immunomodulatory Therapy, JIA = Juvenile Idiopathic Arthritis, MMP = Matrix Metalloproteinases, MTX = Methotrexate, RA = Rheumatoid Arthritis, TB = Tuberculosis, VCAM = Vascular Adhesion Molecules.
29340266 (18)F-FDG PET-CT in a patient with methotrexate-associated lymphoproliferative disorder. 2018 Jan (18)F-FDG PET-CT clearly demonstrated the disease activity of MTX-LPD.
29904314 Cutaneous toxicity of oral low-dose methotrexate. 2018 Jul Chemotherapy-induced acral erythema has been a known side effect of intravenous dosing but has not been reported with oral therapy. Herein we describe two patients receiving treatment with low-dose oral methotrexate who presented with acral erythema. Clinicians and rheumatologists should be aware of this potentially serious side effect of oral chemotherapy in various patient populations. This complication related to methotrexate, though rare, should be anticipated in patients on multiple medications who develop mucocutaneous toxicities.
29862045 Comparison between low disease activity or DAS remission as treatment target in patients w 2018 OBJECTIVES: To compare outcomes of targeted treatment aimed at either low disease activity or remission in patients with early active rheumatoid arthritis (RA). METHODS: Five-year outcomes were compared in 133 patients with early active RA (1987), starting with methotrexate, sulfasalazine and tapered high dose of prednisone (arm 3 of the BehandelStrategieën (Treatment Strategies for Rheumatoid Arthritis) (BeSt) study), targeted at Disease Activity Score (DAS) ≤2.4 (low disease activity), and 175 patients with early RA, starting methotrexate and tapered high dose of prednisone, targeted at DAS <1.6 (selected from IMPROVED study who would have fulfilled inclusion criteria of the BeSt study). Association of treatment target with outcomes DAS <1.6, Boolean remission at year 1 and drug-free DAS remission (DFR) at year 5 were analysed by logistic regression analysis. RESULTS: At baseline, DAS <1.6 steered patients had a milder disease than DAS ≤2.4 steered patients (mean DAS 4.1±SD 0.7vs4.4±0.9, p=0.012) and less radiological damage. DAS decrease, functional ability and radiological damage progression over time were similar in both patient groups. DAS ≤2.4 was achieved in similar percentages in both patient groups, but more DAS <1.6 steered patients achieved DAS <1.6 and DFR. DAS <1.6 steered treatment was associated with achieving DAS <1.6 (OR 3.04 (95% CI 1.64 to 5.62)) and Boolean remission (3.03 (1.45 to 6.33)) at year 1 and DFR at year 5 (3.77 (1.51 to 9.43)). CONCLUSIONS: In patients with early active RA who start with comparable disease-modifying antirheumatic drug+prednisone combination therapy, subsequent DAS <1.6 steered treatment is associated with similar clinical and radiological outcomes over time as DAS ≤2.4 steered treatment; however, in the DAS <1.6 steered group, more patients achieved remission and drug-free remission.
30886984 Atypical presentation of Pneumocystis jirovecii pneumonia in a patient with rheumatoid art 2018 BACKGROUND: We report the case of a patient with rheumatoid arthritis (RA) treated with tofacitinib who developed severe Pneumocystis jirovecii pneumonia (PJP) with an atypical clinical presentation. CASE PRESENTATION: A 78-year old male patient with RA treated with tofacitinib, methotrexate (MTX) and low dose corticosteroids was admitted to the hospital with arthralgia and nausea. Laboratory findings revealed hypercalcemia with normal levels of parathyroid hormone (PTH) and elevated 1,25-(OH)(2) vitamin D levels. A lung CT scan showed bilateral interstitial pneumonic infiltrates. PCR from bronchoalveloar lavage was positive for Pneumocystis jirovecii. Hypercalcemia resolved under PJP treatment and was - after exclusion of other possible causes - probably fungal associated. CONCLUSION: Due to the increased risk of opportunistic infections in immunocompromised patients, the finding of hypercalcemia in conjunction with a pulmonary infection should raise high clinical suspicion of PJP.
30069732 Adult-Onset Still's Disease: Molecular Pathophysiology and Therapeutic Advances. 2018 Aug Adult-onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology generally characterized by persistent high spiking fever, evanescent rash, and polyarthritis. The pathogenesis of AOSD is only partially known. The pivotal role of macrophage cell activation, which leads to T-helper 1 (Th1) cell cytokine activation, is now well-established in AOSD. Moreover, pro-inflammatory cytokines such as interleukin (IL)-1, -6, and -18 seem to play a key role in this disorder, giving rise to the development of new targeted therapies. For years, treatment of AOSD has been largely empirical, using nonsteroidal anti-inflammatory drugs, corticosteroids, and disease-modifying antirheumatic drugs. Patients with steroid- and methotrexate-refractory AOSD can now benefit from efficient and well-tolerated biologic agents such as IL-1, IL-6, and tumor necrosis factor-α antagonists.
30128246 Rapid Response Fluorescence Probe Enabled In Vivo Diagnosis and Assessing Treatment Respon 2018 Aug Diagnosis and early assessment of the treatment response of rheumatoid arthritis (RA) necessitates a reliable bioanalytical method for rapid, sensitive, and specific detection of the hypochlorous acid (HOCl) biomarker in inflammatory diseases. Herein, two fluorescence probes, Probe-1 and Probe-2 are developed for quantitative monitoring and visualization of inflammatory response-related HOCl levels in vitro and in vivo. In the presence of HOCl, fluorescence "OFF-ON" response is obtained for both the probes as a result of specific HOCl-triggered C=N bond cleavage reaction. Probe-1 and Probe-2 feature rapid response (<4 s), a high degree of sensitivity and selectivity toward HOCl, which allow them to be used for quantification of HOCl in a simulated physiological condition. Using Probe-2 as the probe, fluorescence imaging and flow cytometry analysis of HOCl levels in lysosome of inflammatory mimic cells, visualization of HOCl generation in endotoxin-induced inflammation of adult zebrafish and RA of mice are possible. Probe-2 exhibits high effectiveness for early assessment of the treatment response of HOCl-mediated RA in mice with an antiarthritic drug, methotrexate (MTX). The results demonstrate that Probe-2 is a powerful tool for future studies on diagnosis and monitoring treatment efficiency in a broad range of inflammatory diseases, including RA.
29410374 A novel combination of astilbin and low-dose methotrexate respectively targeting A(2A)AR a 2018 Jul Methotrexate (MTX) is widely used for rheumatoid arthritis (RA) treatment with frequently serious adverse effects. Therefore, combination of low-dose MTX with other drugs is often used in clinic. In this study, we investigated the improvement of astilbin and low-dose MTX combination on collagen-induced arthritis in DBA/1J mice. Results showed that the clinic score, incidence rate, paw swelling, pathological changes of joints and rheumatoid factors were more alleviated in combination therapy than MTX or astilbin alone group. Elevated antibodies (IgG, IgG1, IgG2a, IgM and anti-collagen IgG) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-γ and IL-17A) in serum were significantly inhibited, while anti-inflammatory cytokine, IL-10, was enhanced by combination therapy. Further studies indicated that combination therapy significantly decreased Th1 and Th17 cell differentiation and increased Treg cell differentiation. Mechanisms analysis demonstrated combination therapy greatly inhibited Con A-activated MAPK and inflammatory transcriptional signals. Moreover, MTX activated adenosine release and astilbin specifically up-regulated A(2A) adenosine receptor (A(2A)AR) expression simultaneously, which most probably contributed to the synergistic efficacy of combination therapy. ZM241385, a specific antagonist of A(2A)AR, greatly blocked the effects of combination therapy on T cell functions and downstream pathways. All these findings suggest that astilbin is a valuable candidate for low-dose MTX combined therapy in RA via increasing A(2A)AR/adenosine system and decreasing ERK/NFκB/STATs signals.
33418814 Reduction-Responsive Polypeptide Nanogel for Intracellular Drug Delivery in Relieving Coll 2018 Dec 10 Rheumatoid arthritis (RA) induces the destruction of cartilage and bone. Methotrexate (MTX) functions as an effective first-line drug to relieve RA in the clinic. However, patients treated with MTX often suffer from severe side effects mainly due to its off-target effects. Therefore, selective delivery of MTX to the affected joints may achieve upregulated efficacy and safety. The affected joints of RA feature hypoxic microenvironment and increased level of glutathione (GSH), resulting from synovial proliferation, lymphocyte infiltration, and neovascularization. In this study, a disulfide-cross-linked nanogel (NG) of methoxy poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine) (mPEG-P(LP-co-LC)) was synthesized as an intracellular delivery system of MTX. The loading nanogel NG/MTX exhibited apparent reduction-responsiveness and GSH-triggered release behavior of MTX. It also showed efficient internalization and high cytotoxicity toward activated macrophages. Moreover, NG/MTX possessed selective biodistribution in the inflammatory joints of collagen-induced arthritis mouse model. The clinical and histological scores of the mice after NG/MTX treatment were lower than those of the other groups, and the progress of collagen-induced arthritis was overall relieved. To conclude, the controlled delivery of MTX by smart polymer nanoparticles to the RA-affected joints may be a promising approach in the clinical therapy of RA.
29761420 Long-Term Radiographic and Patient-Reported Outcomes in Patients with Rheumatoid Arthritis 2018 Dec INTRODUCTION: Here we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function. METHODS: This was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX. The modified total Sharp score (mTSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were analyzed at month 24 according to disease activity at month 6 defined by the Clinical Disease Activity Index (CDAI) or the Disease Activity Score in 28 joints, C-reactive protein (DAS28CRP). RESULTS: Mean changes from baseline in mTSS at month 24 were less in patients with CDAI remission at month 6 than in those with CDAI moderate/high disease activity (MDA/HDA) at month 6. A DAS28CRP of < 1.9 most closely approximated CDAI remission (≤ 2.8). Tofacitinib appeared to inhibit joint damage in the presence of persistent inflammation compared with MTX. More patients receiving tofacitinib or MTX with CDAI remission or low disease activity (LDA) at month 6 reported normative HAQ-DI scores (< 0.5) at month 24 than did those with CDAI MDA/HDA. CONCLUSION: Regardless of treatment, in both MTX-naïve and MTX-IR patients, remission or LDA at month 6 was associated with successful long-term outcomes: inhibition of structural progression and normative HAQ-DI scores. Long-term outcomes were similar when patients achieved CDAI remission or a DAS28CRP of < 1.9, confirming that this is an appropriate cut-off for remission with DAS28CRP. Tofacitinib potentially inhibits joint damage even with persistent inflammation. FUNDING: Pfizer Inc. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01039688 and NCT00847613.
29574622 Similar Improvements in Patient-Reported Outcomes Among Rheumatoid Arthritis Patients Trea 2018 Jun INTRODUCTION: In patients with rheumatoid arthritis (RA), combination treatment with methotrexate (MTX) and adalimumab is more effective than MTX monotherapy. From the patients' perspective, the impact of reduced MTX doses upon initiating adalimumab is not known. The objective was to evaluate the effects of low and high MTX doses in combination with adalimumab initiation on patient-reported outcomes (PROs), in MTX-inadequate responders (MTX-IR) with moderate-to-severe RA. METHODS: MUSICA was a randomized, double-blind, controlled trial evaluating the efficacy of 7.5 or 20 mg/week MTX, in combination with adalimumab for 24 weeks in MTX-IR RA patients receiving prior MTX ≥ 15 mg/week for ≥ 12 weeks. PROs were recorded at each visit, including physical function, health-related quality-of-life, work productivity, quality-of-sleep, satisfaction with treatment medication, sexual impairment due to RA, patient global assessment of disease activity (PGA), and patient pain. Last observation carried forward was used to account for missing values. RESULTS: At baseline, patients in both MTX dosage groups had similar demographics, disease characteristics, and PRO scores. Overall, initiation of adalimumab led to significant improvements from baseline in the PROs assessed for both MTX dosage groups. Improvements in presenteeism from baseline were strongly correlated with corresponding improvements in SF-36 (vitality), pain, and physical function. Physical and mental well-being had a good correlation with improvement in sleep. Overall, improvements in disease activity from baseline were correlated with improvements in several PROs. CONCLUSIONS: The addition of adalimumab to MTX in MTX-IR patients with moderate-to-severe RA led to improvements in physical function, quality-of-life, work productivity, quality of sleep, satisfaction with treatment medication, and sexual impairment due to RA, regardless of the concomitant MTX dosage. FUNDING: AbbVie. TRIAL REGISTRATION: Clinicaltrials.gov identifier, NCT01185288.
30693040 The effects of conventional drugs in the treatment of rheumatoid arthritis on the serum li 2018 BACKGROUND: Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that leads to damage of human joints. There are various treatment approaches in which different drugs are prescribed which have several alterations in serum lipids. This research aimed to study the effect of RA treatments on the serum lipids. MATERIALS AND METHODS: Two hundred randomly selected patients with RA were randomly assigned to three different groups. The first group of patients was treated with a combination of prednisolone (PRD) and hydroxychloroquine (HCQ). The second group was treated with three drugs including PRD, HCQ, and methotrexate (MTX). The third group was treated with four medications including PRD, HCQ, MTX, and sulfasalazine. Within each group, the lipid factors such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), erythrocyte sedimentation rate, and visual analog scale were measured at the beginning of the experiment and 6 months after exposing the treatments. For each group, we also calculated the Disease Activity Score-28 (DAS-28). The analysis of variance revealed that the overall DAS-28 was significantly different among the three groups. RESULTS: In the first group, the level of TG and TC significantly decreased (P = 0.015 and P ≤ 0.001, respectively). In the second group, the level of TG and LDL significantly decreased (P = 0.009). In the third group, the LDL level increased considerably (P < 0.001). The HDL level significantly increased in all three groups (P = 0.012, P = 0.014, and P = 0.028, respectively). CONCLUSION: The treatment PRD + HCQ + MTX was more effective in reducing the LDL level and increasing the HDL level. To reduce the risk of cardiovascular diseases in patients with RA, it is important to prescribe the combination of drugs which leads and normalizes the lipid profile levels.
29680881 Baricitinib in Patients with Rheumatoid Arthritis and an Inadequate Response to Convention 2018 Jun INTRODUCTION: This article evaluates the efficacy and safety of baricitinib 4 mg versus placebo in United States including Puerto Rico (US) and rest of the world (ROW) subpopulations using data pooled from RA-BEAM and RA-BUILD, which enrolled patients with moderate-to-severe adult-onset rheumatoid arthritis (RA). METHODS: In RA-BEAM, patients with an inadequate response (IR) to methotrexate, at least one X-ray erosion, and high sensitivity C-reactive protein (hsCRP) ≥ 6 mg/L were randomized to placebo or orally administered baricitinib 4 mg daily or subcutaneously administered adalimumab 40 mg every other week. In RA-BUILD, patients with an IR to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) and with hsCRP ≥ 3.6 mg/L were randomized to placebo or baricitinib 2 or 4 mg daily. Patients in both trials were biologic naive. In this post hoc analysis, data from both studies were pooled (714 baricitinib 4 mg-treated, 716 placebo-treated patients). RESULTS: Overall, 188 US and 1242 ROW patients were included. Subgroups differed in baseline characteristics including race, weight, age, time since RA diagnosis, current corticosteroid use, and previous csDMARD use. At weeks 12 and 24, baricitinib-treated patients had larger responses compared to placebo-treated patients for multiple efficacy outcomes: American College of Rheumatology 20/50/70 response, low disease activity, remission, Disease Activity Score 28-C-reactive protein, and Health Assessment Questionnaire-Disability Index. Overall, similar efficacy was observed in US and ROW subgroups with no notable safety differences between subgroups at weeks 12 or 24. CONCLUSION: Baricitinib 4 mg was efficacious compared to placebo in US and ROW subpopulations. Safety was similar between subgroups. FUNDING: Eli Lilly & Company and Incyte Corporation. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01721057; NCT01710358.