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ID PMID Title PublicationDate abstract
30658699 In rheumatoid arthritis, changes in autoantibody levels reflect intensity of immunosuppres 2019 Jan 18 BACKGROUND: Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies like rheumatoid factor (RF), anti-cyclic citrullinated peptide-2 (anti-CCP2), and anti-carbamylated protein (anti-CarP) antibodies. It is currently unclear whether changes in autoantibody levels are associated with disease activity/treatment outcomes and whether they are modified by treatment intensity. Therefore, we determined longitudinal changes in RA-autoantibody levels, the association between these changes and activity score (DAS) and treatment outcomes, and the effect of intensity of immunosuppressive treatment on levels. METHODS: In 381 seropositive RA patients from the IMPROVED study, we measured IgG, IgM, and IgA of anti-CCP2 and anti-CarP; IgM and IgA of RF; and IgG against four citrullinated and two acetylated peptides at 4-month intervals over the first year of treatment. Following initial prednisone and methotrexate (MTX), treatment was changed every 4 months aiming for DAS < 1.6. We investigated changes in autoantibody levels following treatment escalation versus tapering, and the association of levels with DAS over time, EULAR response, and drug-free remission (DFR) ≥ 1 year. RESULTS: For all 14 autoantibodies, levels decreased from 0 to 4 months and then rose until 12 months. Following treatment escalation, autoantibody levels dropped markedly, while they rose following tapering: RF IgM levels, a representative autoantibody, dropped 10% after restarting prednisone and rose 15% aU/mL after tapering MTX (p < 0.0001). There was no association between autoantibody levels and DAS over time or EULAR response. Greater relative changes between 0 and 12 months did not predict DFR (0-12-month relative change RF IgM, - 39% for no DFR (n = 126) and - 16% for DFR (n = 18)). CONCLUSIONS: Changes in RA-autoantibody levels are not associated with DAS or long-term treatment response, but reflect intensity of immunosuppression. This suggests that autoantibody levels are modifiable by current therapies, but that modifying levels is in itself of limited clinical relevance. TRIAL REGISTRATION: ISRCTN11916566 . Registered on 7 November 2006.
30809303 Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methot 2019 Angiogenesis plays an essential role in the progression of rheumatoid arthritis (RA). RGD peptide shows high affinity and selectivity for integrin α(v)β(3,) which is one of the most extensively examined target of angiogenesis. Nimesulide could improve the anti-rheumatic profile of methotrexate. But the clinical application was limited due to water-insolubility of both methotrexate and nimesulide and lacking targeting ability. Therefore, this study aimed to design a targeted drug delivery system of micelles mediated by RGD plus the passive targeting of micelles to solve the application problems of methotrexate and nimesulide (M/N), and thus enhance their combined therapeutic effect on RA. Methods: RGD was conjugated with NHS-PEG-PLA to form RGD-PEG-PLA for the preparation of RGD-modified drug-loaded micelles (R-M/N-PMs). The size and zeta potential of micelles were measured by dynamic light scattering. Morphology was detected by transmission electron microscopy. The inhibition effect of R-M/N-PMs on angiogenesis was assessed by the chick chorioallantoic membrane assay. The real-time fluorescence imaging analysis was conducted to examine the in vivo distribution of the fluorescence-labeled R-M/N-PMs. Rats arthritis model induced by Freund's adjuvant was used to evaluate the in vivo anti-inflammatory efficacy of R-M/N-PMs. Results: The in vitro study indicated successful development of R-M/N-PMs. R-M/N-PMs could markedly suppress the angiogenesis of chick embryos. The fluorescence-labeled R-M/N-PMs mainly accumulated in arthritic joints. RGD enhanced the targeting ability of micelles and thus promoted retention of micelles in arthritic joints. Moreover, R-M/N-PMs significantly alleviated the joint swelling while reducing bone erosion and serum levels of inflammatory cytokines. It helped to recover the bone microstructure of arthritic rats. Conclusion: Our results confirmed that the targeted delivery of the combination of a low dose of methotrexate and nimesulide mediated by RGD-modified polymeric micelles could enhance the therapeutic effect on rheumatoid arthritis. These findings provide a promising potential for the clinical therapy of rheumatoid arthritis.
30944039 Methotrexate use, not interleukin 33, is associated with lower carotid intima-media thickn 2019 Apr 3 BACKGROUND: Rheumatoid arthritis is a risk factor for early mortality due to cardiovascular disease. Interleukin-33 appears to protect against the development of atherosclerosis. The purpose of this study was to investigate the relationship between serum levels of interleukin-33 and its soluble receptor with the presence of subclinical carotid atherosclerosis in rheumatoid arthritis patients. METHODS: Rheumatoid arthritis patients without atherosclerotic disease were subjected to clinical and laboratory assessments, including carotid ultrasound. Interleukin-33 and its soluble receptor serum levels were measured by ELISA. RESULTS: 102 patients were included. The prevalence of carotid plaques was 23.5% and the median intima-media thickness was 0.7 mm. The median interleukin-33 and its soluble receptor concentration was 69.1 and 469.8 pg/ml. No association was found between serum interleukin-33 or its soluble receptor and intima-media thickness or plaque occurrence. Each 0.1 mm increase of intima-media thickness raised the odds of plaque occurrence by 5.3-fold, and each additional year of rheumatoid arthritis duration increased the odds of plaque occurrence by 6%. Each additional year in patients age and each one-point increase in the Framingham Risk Score were associated with a 0.004 mm and 0.012 mm increase in intima-media thickness. Methotrexate use was associated with a 0.07 mm reduction in intima-media thickness. CONCLUSIONS: Interleukin-33 and its soluble receptor were not associated with subclinical atherosclerosis. Traditional risk factors for atherosclerosis and rheumatoid arthritis duration were associated with intima-media thickness and plaque occurrence; methotrexate use was associated with a lower intima-media thickness.
31435754 Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis 2020 Feb Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7 years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1 years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.
30221485 Low Persistence Rates in Patients With Rheumatoid Arthritis Treated With Triple Therapy an 2019 Oct OBJECTIVE: Combination treatments for patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX) alone include the addition of a tumor necrosis factor inhibitor (TNFi) or the addition of sulfasalazine (SSZ) and hydroxychloroquine to MTX (triple therapy). We compared persistence and adherence rates between these 2 combination therapies in US veterans and report the reasons for discontinuation of combination treatment in these groups. METHODS: Using Veteran's Affairs clinical and administrative data from 2006 to 2012, veterans with RA escalating treatment from MTX to MTX-TNFi or triple therapy were examined for a 12-month period after combination initiation. Persistence was defined as treatment without a ≥90-day gap in therapy. Adherence was calculated using the proportion of days covered ≥80% at 12 months. Matching weights-adjusted models were applied to more closely mimic randomization in this study. The reasons that patients discontinued their combination regimens were identified by chart abstraction. RESULTS: Full persistence at 1 year was 45% in the MTX-TNFi patients (n = 2,125) and 18% in the triple therapy patients (n = 171) (P < 0.001). Adherence was higher for the MTX-TNFi group (26%) than the triple therapy group (11%) (P < 0.0001). The triple therapy group was associated with significantly more treatment discontinuation, which was most often due to adverse drug events from SSZ. CONCLUSION: Differences in persistence and adherence between the MTX-TNFi and triple therapy groups appear to be primarily related to adverse drug events that were most often attributed to SSZ.
31037495 Membranous nephropathy caused by rheumatoid arthritis. 2019 Nov Membranous nephropathy (MN) caused by disease-modifying antirheumatic drugs is relatively common in patients with rheumatoid arthritis (RA). However, MN rarely occurs due to RA itself. We describe a 61-year-old woman with RA who showed nephrotic syndrome. She was admitted because of systemic edema and severe arthritis. She had a long history of RA successfully treated with methotrexate (MTX), but discontinued all treatments 4 years before hospitalization. She had never been treated with bucillamine or gold. Laboratory test results were positive for anti-cyclic citrullinated peptide antibody and negative for anti-nuclear antibody. Renal pathologic findings were compatible with MN. Immunofluorescence microscopy showed IgG, IgA, κ, λ, and C3 along the glomerular capillary wall, whereas deposition of IgM or C1q was not detected. In terms of the IgG subclasses, only IgG2 findings were positive. Results for glomerular antigen and serum antibody for M-type phospholipase A2 receptor and thrombospondin type 1 domain-containing 7A were negative. HLA type did not include the HLA-DQA1 gene that is a concern in primary MN (PMN). She responded to intensive immunosuppressive therapy consisting of prednisolone, tacrolimus, and MTX with a parallel reduction of proteinuria. Based on assessments for differentiating PMN from secondary MN (SMN), the diagnosis of the present case was incompatible with PMN. Taken together, we consider that SMN in the present case was due to RA itself rather than drug-induced MN.
30669854 Liquid Chromatography Based Methods for Analysis of Disease-Modifying Antirheumatic Drugs 2019 Rheumatoid arthritis (RA) is a common chronic disease with inflammatory and immunological background where treatments can only improve the symptoms and slow down the progress of the disease. Although there are several drugs with different therapeutic targets available in the market for the treatment of RA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) are the most effective option to date. Methotrexate, azathioprine, hydroxychloroquine, sulfasalazine, leflunomide, minocycline are commonly prescribed DMARDs by rheumatologists but they have the limitations of severe toxicity for which therapeutic drug monitoring is necessary. Many chromatographic methods are available for analysis of these drugs including their metabolites. However, they have not been critically reviewed for pre-chromatographic sample preparation, chromatographic separation and sensitive detection. This review article can be handy for quantitation of DMARDs in diverse biological matrices as it provides comprehensive information on the reported liquid chromatographic methods for last three decades covering all the aspects required for preclinical and clinical studies.
30907116 Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthrit 2019 Sep Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of baricitinib, a recently approved selective Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA), and explore its potential role in therapy. Data Sources: Articles were identified using a PubMed search from inception through January 2019 using the terms rheumatoid arthritis, Olumiant, baricitinib, and LY3009104, its molecular name. Study Selection and Data Extraction: Articles relating to randomized clinical trials, pharmacology, pharmacokinetics, efficacy, and safety of baricitinib were evaluated. Data Synthesis: Baricitinib exerts its effects by inhibiting JAK1 and JAK2 enzymes, targeting cytokine and growth factor receptor stimulation, thus reducing downstream immune cell function. Four trials have demonstrated the efficacy of baricitinib with or without methotrexate in patients naïve to disease-modifying antirheumatic drugs (DMARDs) and those who had an inadequate response to or intolerance to both conventional and biological DMARDs. Furthermore, baricitinib was associated with delayed radiographic progression. Despite baricitinib 4 mg often demonstrating greater efficacy compared with the 2 mg dose, only the 2 mg dose is Food and Drug Administration approved because of safety concerns with the 4 mg dose, primarily thromboembolism. Relevance to Patient Care and Clinical Practice: Baricitinib provides an oral treatment option for patients failing tumor necrosis factor inhibitors (TNFis). Safety, cost, and comparative effectiveness to tofacitinib should be considered prior to prescribing baricitinib. Conclusion: Baricitinib is the second medication in its class and has been proven efficacious for the treatment of RA. Given concerns for adverse effects associated with baricitinib, it should be reserved for patients who have failed one or more TNFis.
31507112 [RITUXIMAB IN RHEUMATOID ARTHRITIS - THERAPEUTIC ASPECTS BASED ON 18 YEARS OF GLOBAL EXPER 2019 Sep Rituximab, a monoclonal antibody against CD20 positive B cell, depletes these cells peripherally, and is a successful treatment in rheumatoid arthritis (RA). It is the second efficacious biologic to be established in the treatment of RA after TNFα blockers. Eighteen years of global experience from diverse clinical trials and from "real world" data, have demonstrated clinical efficacy in various disease scenarios and patient populations - short and long disease duration, methotrexate naïve patients and those with incomplete response to methotrexate, biologic naïve patients and those with incomplete response to previous biologics. Moreover, it has demonstrated the inhibition of radiographic progression. It seems to be most efficacious in seropositive patients. Despite vast experience, the need for concomitant traditional disease-modifying anti rheumatic drugs (DMARD), the optimal retreatment dose, and the favored retreatment interval remain somewhat uncertain. The recommended dosage is 1000 mg, administered twice, with a 2 weeks interval, although in some cases, a reduced dosage of 500 mg, administered twice may be considered. The safety profile of rituximab includes mainly infusion-related reactions, which are usually mild. A small risk of major infections has remained stable over time and repeated courses. Opportunistic infections are infrequent. Nevertheless, reactivation of hepatitis B is still a concern. Tuberculosis, malignancies, cardiovascular events and deterioration of interstitial lung disease do not appear to be increased. Since rituximab severely impairs the humoral response to vaccinations, they should be administered prior to treatment whenever possible. Rituximab has been a powerful addition to the large armamentarium for the treatment of RA. Rituximab is indicated in Israel as a second line biologic treatment for active RA.
30482075 Clinical predictors of inadequate response to conventional synthetic disease-modifying ant 2020 Jan Objectives: To investigate predictors of inadequate response to first conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) including methotrexate (MTX) in untreated rheumatoid arthritis (RA) patients in daily clinical practice.Methods: Inadequate response to MTX or other csDMARDs was defined as being not low disease activity at 12 months in more than 3 of 4 composite measures, and discontinuation or start of biologic DMARDs. The association between baseline factors and csDMARDs-IR was assessed by univariate and multivariate logistic regression analyses.Results: Four hundred and eleven and 146 patients were started on MTX and other csDMARDs, respectively; 218 patients were responsive to MTX, with a response rate of 47.0%. Tender joint count (TJC, ≥6 in 28joints, odds ratio [OR] = 1.67, 95% confidence interval [CI] 1.06-2.64) and CRP (≥1.0 mg/dL, OR = 1.72, 95%CI: 1.10-2.70) at baseline were identified as predictors on multivariate logistic regression analysis. TJC (OR = 3.60, 95%CI: 1.29-10.00) was the factor identified as a predictor of the development of other csDMARDs-IR.Conclusion: In this observational study, patients with untreated RA at risk of inadequate response to MTX included those with a higher TJC and higher CRP, while a higher TJC was the only independent predictor of an inadequate response to csDMARDs other than MTX.
30913494 Enhanced skin permeation of Methotrexate from penetration enhancer containing vesicles: In 2019 Jun Low dose Methotrexate (MTX) therapy is considered a gold standard for Rheumatoid Arthritis (RA). Transdermal drug delivery is hypothesized as an alternative to conventional therapies to alleviate its adverse effects. In our study, MTX was entrapped in deformable liposomes and loaded in a hydroxyethyl cellulose gel. This system was evaluated by the Box Behnken statistical design for optimization. The effect of formulation variables on particle size, entrapment and ex vivo skin permeation was studied. The MTX nanogel was evaluated for its dermal toxicity (acute and repeat dose safety), in vivo biodistribution (using (125)I radio-labelled MTX) and therapeutic efficacy (collagen induced arthritis [CIA] model). The optimized formulation demonstrated appreciable nanosize (110 ± 20 nm), drug entrapment (42 ± 1.9%) and high ex vivo transdermal flux (17.37 ± 1.5 μg/cm2/hr). In the dermal toxicity studies, nanogel formulation did not show any signs of irritation or toxicity, whereas in the biodistribution study, the MTX nanogel formulation depicted sustained systemic delivery up to 48 h with low accumulation in its organs of toxicity such as the liver, kidneys and gut. In the CIA model, the MTX nanogel significantly ameliorated hind paw swelling, reduced arthritic score, joint damage (histological, radiological examination) and attenuated the rise in serum cytokines such as TNF-ɑ and IL-6. In conclusion, the optimized MTX nanogel formulation displayed skin biocompatibility, sustained systemic delivery, safety as well as therapeutic efficacy.
31495833 Nanoparticle-delivered siRNA targeting Bruton's tyrosine kinase for rheumatoid arthritis t 2019 Nov 1 Rheumatoid arthritis (RA) is a systemic autoimmune disease that can cause irreversible joint deformity. There is still no cure for RA, and current therapeutics, including methotrexate and adalimumab, cause serious off-target effects and systemic immunosuppression, which in turn increases the risk of infection. Bruton's tyrosine kinase (BTK) in macrophages and B cells has been demonstrated to be a promising therapeutic target for RA. However, high doses of BTK inhibitors are required for efficient BTK suppression, which limits their clinical use. Small interfering RNA (siRNA) is promising for the silencing of specific genes and has been used for the treatment of multiple diseases. To deliver siRNA into macrophages and B cells for BTK gene silencing, we employed cationic lipid-assisted PEG-b-PLGA nanoparticles (CLANs) to encapsulate siRNA. We demonstrated that macrophages and B cells were able to efficiently ingest the CLANs both in vitro and in vivo. Thereafter, we encapsulated siRNA targeting BTK (siBTK) into the CLANs, denoted as CLAN(siBTK), and demonstrated that CLAN(siBTK) significantly inhibited BTK expression in macrophages and B cells. In a collagen-induced mouse arthritis model, CLAN(siBTK) treatment dramatically reduced joint inflammation and other RA symptoms but showed no toxicity, proving that using CLAN(siBTK) is a promising approach for RA therapy.
30523477 Granuloma annulare development in a patient with rheumatoid arthritis treated with tociliz 2019 Feb Granuloma annulare (GA) is the most common non-infectious disease. Despite the fact that it is a benign disease, it can be associated with a variety of disorders and certain drugs including biological disease-modifying anti-rheumatic drugs (bDMARDs). A 50-year-old man with a history of rheumatoid arthritis refractory to methotrexate, hydroxychloroquine and infliximab was treated with tocilizumab (TCZ), an interleukin-6 receptor antagonist, 162 mg subcutaneously every week. The patient responded very well to TCZ treatment with a decrease of acute phase reactants and reduction of disease activity score for 28-joints count. However, 3 months later he developed erythematous polycyclic eruptions affecting the lower extremities consistent with a diagnosis of GA which was confirmed by a skin biopsy. TCZ has been discontinued and the patient was treated with prednisone presenting complete resolution of skin manifestations after 4 weeks. This is the first case of GA development during TCZ treatment. Thus, we review the literature and discuss the relevant cases of GA development in patients treated with bDMARDs. When dealing with patients treated with these agents, all physicians should be aware of possible adverse events and the potential development of such complications.
29273497 Methotrexate in patients with rheumatoid arthritis in Spain: Subanalysis of the AR Excelle 2019 Nov OBJECTIVE: The AR Excellence project evaluates clinical monitoring in patients with rheumatoid arthritis (RA) in Spain. The aim of the study was to analyze the use of methotrexate (MTX) in the AR Excellence cohort and to compare it with current recommendations. PATIENTS AND METHODS: We collected data from RA patients who initiated treatment with MTX. They included demographics, dose and routes of administration, switching among them, highest dose in each route, combinations with other disease-modifying antirheumatic drugs (DMARDs), time to combination with another DMARD (either conventional or biological) and adverse events. RESULTS: Six hundred twenty-five patients with RA (mean age 55 years; 70.6% women) were included, with an average disease duration of 21 months. Ninety percent of the patients initiated treatment with MTX. Therapy was begun with a mean dose of 11mg per week; this initial dose was increased in 58% of the individuals. The average time to reach the full dose of MTX (20mg a week) was 6,67 months. Time to combination of MTX with another DMARD, either synthetic or biological, was 3 months. In all, 67.4% of the patients received oral MTX and the route was subcutaneous in 18.6%. In 12% of the cases, there was a change in the route of administration after a period of 6 months. In 544 patients, folate supplements were added to MTX; MTX-related adverse events were detected in 17.3% of the patients. CONCLUSION: MTX is currently the pivotal treatment in RA. The subanalysis of the AR Excellence project demonstrates that MTX escalation to its full doses is not done with adequate speed. The subcutaneous route is used in a small proportion of patients.
31104217 Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response t 2019 Sep OBJECTIVE: To evaluate the efficacy and safety of diacerein in patients with rheumatoid arthritis (RA) who are methotrexate inadequate responders (MTX-IR). METHOD: In this pilot, multicenter, double-blind, placebo-controlled trial, MTX-IR RA patients were randomized to either diacerein or matching placebo as add-on treatment to MTX for 24 weeks. Efficacy and safety were evaluated every 4 weeks until week 28. Primary and secondary efficacy endpoints were the percentage of patients achieving the ACR20 criteria and a moderate EULAR response at week 24, respectively. RESULTS: Forty patients were equally randomized to both study treatments; 16 and 19 participants completed the study in the diacerein and the placebo arms, respectively. Baseline characteristics were similar in both groups, except that tender joint count, DAS28-ESR score, and non-steroidal anti-inflammatory drug consumption were higher in the placebo arm. The ACR20 response at week 24 was similar in the diacerein and placebo groups (65% vs 45%, P = .20). However, treatment response according to the EULAR criteria was better in patients taking diacerein (75% vs 25% of moderate response, P = .002). In the 35 patients with assessments through week 28, diacerein was superior to placebo in ACR20 at weeks 24 and 28 (both 81% vs 47%, P = .04). Incidence of adverse events was comparable in both arms, with only chromaturia being more common with diacerein than placebo (40% vs 10%, P = .03). CONCLUSIONS: These preliminary results show the potential benefits of diacerein on pain, joint function, and disease activity in MTX-IR RA patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01264211 Key Points • Diacerein has shown positive effects on rheumatoid arthritis symptoms. • A good safety profile of diacerein has been observed when it was administered as add-on therapy to methotrexate in patients with rheumatoid arthritis.
30396592 Added value of combining methotrexate with a biological agent compared to biological monot 2019 Jun OBJECTIVES: To assess the efficacy and safety of methotrexate (MTX) in combination with an approved biological agent compared to biological monotherapy, in the management of patients with rheumatoid arthritis (RA). METHODS: MEDLINE, EMBASE, CENTRAL and other sources were searched for randomised trials evaluating a biological agent plus MTX versus the same biological agent in monotherapy. Co-primary outcomes were ACR50 and the number of patients who discontinued due to adverse events (AEs). Random-effects models were applied for meta-analyses with risk ratio and 95% confidence intervals and the GRADE approach was used to assess confidence in the estimates. RESULTS: The analysis comprised 16 trials (4965 patients), including all biological agents approved for RA except anakinra and certolizumab. The overall likelihood of responding to therapy (i.e. ACR50) after 6 months was 32% better when MTX was given concomitantly with biological agents (1.32 [1.20-1.45]; P < 0.001) corresponding to 11 more out of 100 patients (7-16 more); Moderate Quality Evidence. Discontinuing due to AEs from concomitant use of MTX was potentially 20% increased (1.21 [0.97-1.50]; P = 0.09) compared to biological monotherapy corresponding to 1 more out of 100 patients (0-3 more); Moderate Quality Evidence. CONCLUSIONS: Randomised trials provide Moderate Quality Evidence for a favourable benefit-harm balance supporting concomitant use of MTX rather than monotherapy when prescribing a biological agent in patients with RA although in absolute terms only 7-16 more out of 100 patients will achieve an ACR50 response after 6 months of this combination therapy.
31142786 Herbo-mineral formulation 'Ashwashila' attenuates rheumatoid arthritis symptoms in collage 2019 May 29 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects joints of hands and feet and introduces injury in secondary organs such as cardiac tissue. In the present study, we induced RA in male Balb/c mice (CAIA) using collagen-antibody cocktail (C-Ab) and lipopolysaccharide intraperitoneal injections. Induction of RA in the animals was detected through the loss of body weight, food, and water consumption, pedal edema, increased arthritis score of the paw and ankle, increase in radiological and histological lesion score of ankle and knee joints and enhanced pain perception in the C-Ab induced RA animals. Ashwashila is a herbo-mineral medicine from Indian Ayurvedic system. Human equivalent doses of Ashwashila (ASHW) and standard of care, Methotrexate were given to the CAIA animals for two weeks. ASHW treatment significantly reversed the effect of C-Ab with reduced pedal edema, arthritis score, radiological and histological lesion scores in ankle-joint, knee-joint and articular cartilage, reduced pain perception. These effects were comparable with the Methotrexate treatment. In human monocytic (THP-1) cells, ASHW was found to be biocompatible at in-vitro test doses. The anti-arthritis mechanism of action for ASHW was established through the suppression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α; and upstream regulator, NF-κB. Taken together, we show the pre-clinical efficacy of ASHW in reducing RA associated symptoms by controlling inflammation and suggest it as a potential therapeutic candidate for rheumatoid arthritis.
30907366 [Late-onset rheumatoid arthritis: clinical, biological, and therapeutic features About a r 2019 Mar 1 Rheumatoid arthritis (RA) is the most common chronic inflammatory rheumatism in adults. The objective of our study was to analyze the clinical, biological and therapeutic characteristics in subjects over 60 years old. PATIENTS AND METHODS: We performed a retrospective, monocentric, descriptive study on medical records consultations. The data collection concerned subjects over 60 years of age who had been diagnosed with "rheumatoid arthritis" in the rheumatology and internal medicine departments of CHU Reims over a period stretching from 2010 to 2015. RESULTS: Thirty-two patients were included in our study for this period. The mean age of diagnosis was 66.6 years, for a median age of 67.5 years (min: 60 years, max: 88 years). There were 22 female (69%) and 10 male (31%) patients, with a sex ratio H/F of 2.2. The mean duration of symptom progression before diagnosis was 33.2 months. What dominates our series is the inaugural involvement of the interphalangeal proximal, wrists, shoulders and metacarpophalangeal for the vast majority of cases. Oral corticosteroids were used in 27 patients and were the only treatment in 3 patients. Methotrexate (MTX) was introduced in 27 patients. Nine patients received biotherapy: it was tocilizumab (Roactemra®) for 5 patients, adalimumab (Humira®) for 2 patients, abatacept (Orencia®) for 2 patients, etanercept (Enbrel®) for 2 patients, golimumab (Simponi®) for 1 patient and infliximab (Remicade®) for one patient. In our series, 7 patients are over 75 years old at the time of diagnosis of RA. CONCLUSION: The rheumatoid arthritis of the elderly remains a common condition and constitutes a diagnostic and therapeutic challenge. Because of the co-morbidities, the clinician's perception of the patient's overall condition and the inaccuracies in the use of certain molecules in these patients, under-treatment may, on the contrary, weaken a patient whose remission will be postponed. This was not the case in our series, with a methodical use of methotrexate as well as effective dose biotherapies.
31555886 Assessment of cognitive function in female rheumatoid arthritis patients: associations wit 2020 Apr We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.
30917076 Adherence, Persistence, and Expenditures for High-Cost Anti-Inflammatory Drugs in Rheumato 2019 Apr BACKGROUND: Drugs for inflammatory conditions are one of the highest expenditure therapeutic classes for health plans. Published literature for adherence, persistence, nonadherence risk factors, and health care costs are incomplete for newer biologic agents. OBJECTIVES: To (a) examine differences in adherence, persistence, switch patterns, and health care costs among high-cost specialty anti-inflammatory medications and (b) suggest risk factors for nonadherence in rheumatoid arthritis. METHODS: In this exploratory retrospective cohort study, we used medical and pharmacy claims from 1.2 million enrollees in commercial health plans administrated by Premera Blue Cross, the largest not-for-profit health plan in the Pacific Northwest. We included members with rheumatoid arthritis who used the following high-cost disease-modifying antirheumatic drugs: abatacept, adalimumab, anakinra, apremilast, certolizumab, etanercept, golimumab, infliximab, rituximab, sekukinumab, tocilizumab, tofacitinib, and ustekinumab. Adherence was calculated via medication possession ratio. Persistence was calculated as the amount of days between the initial fill and final fill plus days supply. Switch rates for adalimumab and etanercept were calculated as the percentage of members who switched to another target drug during the observation period. Direct medical costs (total health care costs) and health care costs excluding specialty agents were calculated using the net allowable amount per claim for the duration of each therapy. Adherence, persistence, and costs of care were also examined for concurrent methotrexate use for the most used target drugs. RESULTS: The most commonly used drugs were abatacept (n = 47), adalimumab (n = 226), and etanercept (n = 252). Nonadherence in certain subgroups was associated with higher mean monthly health care costs, excluding specialty agents (etanercept cohort: +$1,063 for nonmethotrexate users; +$492 for nonadherent methotrexate users), but adherence was associated with higher total health care costs (+$883 for etanercept). Relative to specialty pharmacies, retail was associated with 9% higher nonadherence. Concurrent methotrexate use was associated with higher persistence (+307 and +192 days with adalimumab and etanercept). The most commonly switched-to drug after adalimumab/etanercept was abatacept (n = 39). CONCLUSIONS: This exploratory study raises signals suggesting that retail pharmacies may be associated with higher nonadherence; nonadherence may be associated with increased health care costs, excluding specialty agents; adherence may increase total health care costs; and methotrexate use may be associated with increased persistence. Future research should confirm these findings. DISCLOSURES: This research was part of an internship awarded to Khilfeh by the AMCP Foundation/Pfizer Summer Internship Program and funded by Pfizer. Gross is an employee of Pfizer. The other authors have nothing to disclose. A portion of this research was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting as a continuing education session entitled "The Evolving Role of Real-World Data in Health Care Decision Making" on March 29, 2017, in Denver, CO, and at AMCP Nexus 2016 as a poster on October 3-6, 2016, in National Harbor, MD.