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ID PMID Title PublicationDate abstract
32896694 Medicare expenditures for conventional and biologic disease modifying agents commonly used 2020 Oct BACKGROUND: Biologic disease modifying agents (bDMARDs) are an integral part of rheumatoid arthritis treatment guidelines but are associated with significant cost in the US. We present the trends in total spending and unit cost of conventional DMARDs (cDMARDs) as compared to bDMARDs in Medicare program. METHODS: We used the Medicare drug spending data for the year 2012-2017 covering all part B (fee-for-service) and part D drugs. Total spending was calculated by summing spending across various drug formulations and unit drug cost by dividing total spending by number of doses dispensed. We present the 6-year trends in total spending, total beneficiary count and unit costs of each of the commonly used cDMARDs and bDMARDs. RESULTS: Between 2012 and 2017, the total spending on the cDMARDs increased 5-folds from $98 million to $579 million; this was fraction of total spending on bDMARDs which increased from $4.3 to $10.0 billion. This increase was driven largely by unit costs of drug rather than number of beneficiaries. There was a 6-fold increase in the unit cost of generic hydroxychloroquine followed by methotrexate and leflunomide. Amongst bDMARDs, adalimumab and etanercept unit cost increased by 2-folds. The increase was less pronounced for office-administered products. CONCLUSIONS: Despite the availability of several generic cDMARDs over decades, there were steep increases in the unit cost of these agents to "keep pace" with the increases in bDMARDs. As the number of elderly rheumatoid arthritis patients increases, policy interventions might be required to reduce the spending on both biologics and conventional DMARDs.
31792368 Genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate 2020 Jun The objective of the study is to develop genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Among RA patients treated with MTX, 1966 polymorphisms of 246 enzymes/transporters relevant to pharmacokinetics and pharmacodynamics were measured by the Drug Metabolism Enzymes and Transporters (DMET) microarray and direct sequencing, and clinical variables at baseline were collected. For efficacy, response criteria of the European League Against Rheumatism were used to classify patients as responders or non-responders. Hepatotoxicity was defined as elevations of aspartate aminotransferase or alanine aminotransferase ≥1.5 times the reference range upper limit. Among 166 patients, a genetic prediction model for efficacy using seven polymorphisms showed the area under the receiver operating characteristic curve (AUC) was 0.822, with 74.3% sensitivity and 76.8% specificity. A combined genetic and clinical model indicated the AUC was 0.844, with 81.5% sensitivity and 76.9% specificity. By incorporating clinical variables into the genetic model, the overall category-free net reclassification improvement (NRI) was 0.663 (P < 0.0001) and the overall integrated discrimination improvement (IDI) was 0.083 (P = 0.0009). For hepatotoxicity, a genetic prediction model using seven polymorphisms showed the AUC was 0.783 with 70.0% sensitivity and 80.0% specificity, while the combined model indicated the AUC was 0.906 with 85.1% sensitivity and 87.8% specificity (overall category-free NRI: 1.002, P < 0.0001; overall IDI: 0.254, P < 0.0001). Our genetic and clinical models demonstrated moderate diagnostic accuracy for MTX efficacy and high accuracy for hepatotoxicity. These findings should, however, be validated and interpreted with a caution until external validation.
32907614 The multi-biomarker disease activity test for assessing response to treatment strategies u 2020 Sep 9 OBJECTIVES: The CAMERA-II trial compared two tight-control, treat-to-target strategies, initiating methotrexate with prednisone (MTX+pred) or MTX with placebo (MTX+plac), in early RA-patients. The multi-biomarker disease activity (MBDA) blood test objectively measures RA disease activity with a score of 1-100. In CAMERA-II, response profiles of the MBDA score, its individual biomarkers, and DAS28 were assessed. METHODS: We evaluated 92 patients from CAMERA-II of whom clinical data and serum for MBDA testing at baseline and ≥ 1 time-point from months 1, 2, 3, 4, 5, 6, 9, or 12 were available. Changes (∆) from baseline for DAS28 and MBDA score and comparisons of ∆DAS28 and ∆MBDA score over time within the MTX+pred versus the MTX+plac strategy were tested for significance with t tests. Changes in biomarker concentration from baseline to months 1-5 were tested with Wilcoxon signed rank test and tested for difference between treatment arms by Mann-Whitney U test. RESULTS: MBDA and DAS28 showed similar response profiles, with gradual improvement over the first 6 months in the MTX+plac group, and in the MTX+pred group faster improvement during month 1, followed by gradual improvement. The 12 MBDA biomarkers could be grouped into 4 categories of response profiles, with significant responses for 4 biomarkers during the MTX+plac strategy and 9 biomarkers during the MTX+pred strategy. CONCLUSIONS: MBDA tracked treatment response in CAMERA-II similarly to DAS28. More individual MBDA biomarkers tracked treatment response to MTX+pred than to MTX+plac. Four response profiles could be observed. TRIAL REGISTRATION: CAMERA-II International Standard Randomised Controlled Trial Number: ISRCTN 70365169 . Registered on 29 March 2006, retrospectively registered.
33078254 Methotrexate use does not increase the prevalence of hepatic steatosis: a real-world retro 2021 May OBJECTIVE: We aimed to determine whether methotrexate (MTX) treatment in patients with rheumatoid arthritis (RA) leads to the development of non-alcoholic fatty liver (NAFL). METHOD: Data were derived from records of all patients with RA who underwent abdominal ultrasonography at the Jeonbuk National University Hospital. Patients with ultrasound-proven NAFL were identified, and those without NAFL were matched by age and sex using the propensity score matching method at 1:3 ratio. We also analyzed the Health Insurance Review and Assessment Service-National Patient Samples, a nationwide cohort database, to determine the association between MTX use and NAFL in a large number of patients (n = 24,653). RESULTS: In the hospital cohort, 92 patients with NAFL did not show significant differences in the cumulative MTX dose when compared with the no-NAFL group (n = 276) (1908.5 ± 1757.5 vs. 1948.6 ± 2118.8 mg, p = 0.911). The prevalence of NAFL was not significantly different across strata of cumulative MTX dose. Multiple logistic analyses identified hypertriglyceridemia (OR, 4.88 [95% CI, 1.13-20.93]) and higher body mass index (OR, 1.22 [95% CI, 1.05-1.41]) as being associated with an increased risk of NAFL. In the nationwide cohort, the MTX exposure rate between the NAFL and no-NAFL groups was not significantly different. CONCLUSIONS: Collectively, no significant association between NAFL development and administration of MTX was detected in this study. Our results suggest that it is more efficient to adjust for individualized risk factors for NAFL prevention rather than discontinuation of MTX in patients with RA. Key Points • NAFLD has been highlighted with increasing prevalence worldwide and possible progression to end-stage liver disease. • Cumulative dose or exposure history of MTX does not show a significant association with NAFLD prevalence. • Modifying well-established risk factors is more efficient in NAFLD prevention rather than discontinuation of MTX.
32033935 Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucoco 2020 Apr BACKGROUND: In rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes. OBJECTIVES: To determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy. METHODS: Data of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed. RESULTS: No statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms. CONCLUSION: No effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.
33023661 Radiographic remission in rheumatoid arthritis quantified by computer-aided joint space an 2020 Oct 6 BACKGROUND: The reduction of finger joint space width (JSW) in patients with rheumatoid arthritis (RA) is strongly associated with joint destruction. Treatment with certolizumab pegol (CZP), a PEGylated anti-TNF, has been proven to be effective in RA patients. The computer-aided joint space analysis (CAJSA) provides the semiautomated measurement of joint space width at the metacarpal-phalangeal joints (MCP) based on hand radiographs. The aim of this post hoc analysis of the RAPID 1 trial was to quantify MCP joint space distance (JSD-MCP) measured by CAJSA between baseline and week 52 in RA patients treated with certolizumab pegol (CZP) plus methotrexate (MTX) compared with MTX/placebo. METHODS: Three hundred twenty-eight patients were included in the post hoc analysis and received placebo plus MTX, CZP 200 mg plus MTX and CZP 400 mg plus MTX. All patients underwent X-rays of the hand at baseline and week 52 as well as assessment of finger joint space narrowing of the MCP using CAJSA (Version 1.3.6; Sectra; Sweden). The joint space width (JSW) was expressed as mean joint space distance of the MCP joints I to V (JSD-MCP(total)). RESULTS: The MTX group showed a significant reduction of joint space of - 4.8% (JSD-MCP(total)), whereas in patients treated with CZP 200 mg/MTX and CZP 400 mg/MTX a non-significant change (JSD-MCP(total) + 0.6%) was observed. Over 52 weeks, participants with DAS28 remission (DAS28 ≤ 2.6) exhibited a significant joint space increase of + 3.3% (CZP 200 mg plus MTX) and + 3.9% (CZP pegol 400 mg plus MTX). CONCLUSION: CZP plus MTX did not reduce JSD-MCP(total) estimated by CAJSA compared with MTX/placebo. Furthermore, clinical remission (DAS28 ≤ 2.6) in patients treated with CZP plus MTX was associated with an increasing JSD, indicating radiographic remission in RA.
32472463 Immune checkpoint inhibitor-induced inflammatory arthritis: a novel clinical entity with s 2020 Dec OBJECTIVE: To determine the clinical and serologic similarities and differences between inflammatory arthritis induced by immune checkpoint inhibitors (IA-irAE) and rheumatoid arthritis (RA). METHODS: In this retrospective cross-sectional comparative study, 20 patients with IA-irAE were age and sex matched to 40 seropositive and 40 seronegative RA patients. Electronic medical records were reviewed from diagnosis of inflammatory arthritis through May 2019. Arthritis characteristics, treatment, and relevant laboratory and serologic studies were captured. RESULTS: Clinically, IA-irAE differed from seropositive and seronegative RA with respect to disease duration (4.18 versus 11.59 and 13.3 months, respectively, p = 0.005 (IA-irAE vs seropositive RA), p = 0.002 (IA-irAE vs seronegative RA)), polyarticular joint involvement at presentation (75% versus 97.5% and 100%, p = 0.013, p = 0.003), absence of erosive changes (5.9% vs 43.6% and 53.8%, p = 0.005, p = 0.001), mean prednisone dose (24.7 mg versus 16.53 mg and 15.68 mg, p = 0.008, p = 0.005), and use of methotrexate (5.0% versus 85.0% and 70.0%, p < 0.0001, p < 0.0001). Serologically, IA-irAE closely resembled seronegative RA. ANA positivity was seen in a minority of patients and did not differ significantly between all groups; however, the ANA staining pattern (speckled) was similar between IA-irAE and seronegative RA (100% versus 75%, respectively) and was not commonly observed in seropositive RA (18.2%). CONCLUSION: IA-irAE is a new subset of IA that resembles seronegative RA immunologically. Our findings suggest that further study of IA-irAE might provide a window into underlying pathogenic mechanisms of early-stage seronegative RA. Key Points • Comprehensive comparison of clinical features between inflammatory arthritis irAE (IA-irAE) and regular rheumatoid arthritis indicates IA-irAE as a new subset of inflammatory arthritis. • IA-irAE resembles seronegative RA immunologically, suggesting that study of IA-irAE may provide a window into underlying pathogenic mechanisms of early-stage seronegative RA.
33238812 Primary cutaneous diffuse large B-cell lymphoma, leg type, in a patient with rheumatoid ar 2021 Jul An 84-year-old woman, who was diagnosed with rheumatoid arthritis (RA) and was treated with methotrexate and, subsequently, etanercept (ETN) for 6 years, presented with rapidly progressing painful cutaneous mass on the right medial malleolus. The patient was eventually diagnosed with primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT). ETN therapy was promptly discontinued expecting spontaneous regression of the lymphoma, which was thought to have developed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders. However, no tumour regression was noted. Chemoimmunotherapy was subsequently initiated, which resulted in partial remission. PCLBCL-LT rarely occurs in patients with RA. Here, we report the first case of PCLBCL-LT that developed in a patient with RA receiving ETN therapy.
32097471 Predictors of presenteeism, absenteeism and job loss in patients commencing methotrexate o 2020 Oct 1 OBJECTIVES: Work is an important health outcome. This study aimed to identify predictors of work loss, absenteeism and presenteeism over 1 year in RA patients commencing treatment with MTX or biologics. METHODS: Patients aged 18-65 years in full/part-time employment from two UK prospective cohorts were included: MTX-starters = Rheumatoid Arthritis Medication Study; and biologic-starters = Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate. Presenteeism and absenteeism were assessed using the RA-specific Work Productivity Survey at baseline, and 6 and 12 months. Potential predictors including baseline age, gender, clinical measures (e.g. disability, pain, fatigue), psychological distress, occupation and EULAR response from baseline to 6 months were investigated. RESULTS: A total of 51/463 MTX-starters and 30/260 biologic-starters left work over 12 months. Higher baseline psychological distress in MTX-starters [odds ratio (OR) 1.1 (95% CI: 1.0, 1.1)] and higher disability in biologic-starters [OR 3.5 (95% CI: 1.4, 8.6)] predicted work loss. Some 16.1% of patients reported sick-leave, which was predicted by disability [OR (95% CI): MTX-starters: 1.5 (0.9, 2.3); biologic-starters: 2.4 (1.1, 5.2)]. Median presenteeism scores were very low (minimal interference) in both cohorts. Higher fatigue for MTX starters [incidence rate ratio 1.2 (95% CI: 1.0, 1.4)] and higher disability in biologic-starters (incidence rate ratio 1.4 (95% CI: 1.1, 1.7)] predicted presenteeism. Good EULAR response was associated with lower absenteeism and presenteeism in both cohorts. CONCLUSION: Patients with RA still face significant limitations regarding their ability to work. Disability and EULAR response were the main predictors of work outcomes, emphasizing the need to control the disease and the importance of function in enabling work participation.
31350056 Different risk profiles of biologic agents for new-onset psoriasis in patients with rheuma 2020 Feb OBJECTIVE: To investigate rates and risk factors for incident and recurrent psoriasis in rheumatoid arthritis (RA) patients treated with different biologic (b) and conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). METHODS: RA patients enrolled in the German biologics register RABBIT without (n = 14,525) or with a history of psoriasis (n = 375) were analyzed separately. All first events of psoriasis reported until October 2017 were assigned to the treatments prescribed in the previous 3 months. Crude incidence rates (IR) of psoriasis were calculated per 1000 patient-years. To investigate risk factors for psoriasis, cox regressions with and without inverse probability weights were applied to adjust for confounding by indication. RESULTS: 117 incident and 37 recurrent psoriatic events were reported. Patients exposed to TNFi had a significantly higher incidence rate (IR = 3.04/1,000 PY) than those exposed to csDMARDs only (IR = 0.65), whereas IRs for abatacept, rituximab and tocilizumab did not differ significantly from csDMARDs. Adjusted Cox regression confirmed a higher risk for TNFi. Female sex (HR: 1.7) and smoking (HR: 2.1) were significantly associated with incident psoriasis while methotrexate decreased the risk (HR: 0.5). For recurrent psoriasis, IRs for TNFi, abatacept and rituximab were significantly higher than for csDMARDs. CONCLUSIONS: Our data confirm a previously observed increased risk of incident psoriasis in patients exposed to TNFi compared to csDMARDs. However, the overall risk is low and the event is usually non-serious. Comedication of TNFi with methotrexate seems to lower the risk of incident psoriasis. In patients with a history of psoriasis, recurrence as adverse event is rare.
32760165 Gene expression regulated by abatacept associated with methotrexate and correlation with d 2020 OBJECTIVES: Abatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data. METHODS: In this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept. RESULTS: In methotrexate/Abatacept responders, 672 genes were significantly (q<0.05) dysregulated at 6 months compared to baseline. Correlation analysis highlighted 19 genes whose dysregulations were significantly associated with disease activity variation (p<0.05) and whose functions were associated with proliferation, apoptosis of cells and mitochondrial metabolism, suggesting a restoration of oxidative signaling. The other 653 gene expression changes were relative to direct or indirect effects of methotrexate/Abatacept treatment and were significantly (p<0.005) involved in pathways relative to mRNA processing, proteasome, angiogenesis, apoptosis and TCR signaling. This study highlights new mechanisms of action of methotrexate/Abatacept and may provide new therapeutic targets to prevent autoimmunity in rheumatoid arthritis.
32189595 Liver Fibrosis in Rheumatoid Arthritis Patients Treated with Methotrexate. 2020 INTRODUCTION: Methotrexate (MTX) is a highly effective therapy for patients with rheumatoid arthritis (RA). However, it has been associated with a range of liver related adverse events. The aim of our study was to evaluate the prevalence rate of liver fibrosis in RA patients and to assess the correlation of cumulative MTX dose with hepatic fibrosis in our context. MATERIALS AND METHODS: This is a cross-sectional study, whose goal is to describe and analyze the factors correlated with the liver fibrosis in RA patients treated with methotrexate especially the cumulative dose of MTX, along the period lying between January 2012 and March 2019. The study was carried out in the Rheumatology Department of the University Hospital Hassan II of Fez. The patients have met the assessment of the ACR 2010 criteria. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis. A value of p <0.05 has been used to identify factors associated with liver fibrosis. RESULTS: A total of 319 patients with RA were recruited who were on MTX treatment. There were 276 female and 43 male patients (female: male ratio of 6.3). The average age was 53 years + /-12.4 years. The average duration of symptoms was 10.68 +/-6.9 years. RA was seropositive for the rheumatoid factor or the anti-ccp in 90.3 %. Six patients (2%) had developed liver fibrosis while on MTX therapy. In the bivariate analysis, the liver fibrosis is significantly related to the hepatic cytolysis (p<0.001) and to the combination of MTX with other DMARDs (p<0.05). However, the multiple logistic regression analysis did not find any significant association between the groups. CONCLUSION: In our context, the prevalence rate of hepatic fibrosis in patients with rheumatoid arthritis under methotrexate is low. It is seen much more in patients treated with methotrexate in combination with other disease-modifying anti-rheumatic drugs (DMARDs). These results require confirmation in a larger number of patients.
32159414 Clinical aspects in patients with rheumatoid arthritis complicated with lymphoproliferativ 2021 Jan OBJECTIVES: To identify predictive factors for lymphoproliferative disorders (LPDs) that persist after methotrexate (MTX) withdrawal (Persistent-LPD) and the optimal treatment for rheumatoid arthritis (RA) after LPD regression. METHODS: Among 3666 patients with RA treated with MTX in our department from 2006 to 2017, 26 cases of LPD that regressed after MTX withdrawal (Regressive-LPD) and 25 cases of Persistent-LPD were compared. Multivariate logistic analysis was performed to identify predictive factors for Persistent-LPD. Retention rates of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated using the Kaplan-Meier Method. RESULTS: In Persistent-LPD, the incidence of diffuse large B-cell lymphoma was higher (76%). The overall 2-year survival rate was 83.9%: 95.8% for Regressive-LPD and 71.0% for Persistent-LPD. The International Prognostic Index (IPI) risk classification was useful for predicting Persistent-LPD. bDMARDs were introduced in 38 RA patients after LPD regression. Unadjusted retention rate of bDMARDs in the 51 LPD patients was significantly lower than that in the 1668 non-LPD RA patients in our bDMARD cohort (controls) (p = 0.029). The 1-year retention rates for bDMARDs were 69% and 64% for tocilizumab and abatacept, respectively vs. 46% for TNF-inhibitor (TNFi). CONCLUSION: Risk assessment using IPI predicted Persistent-LPD. After LPD regression, non-TNFi tended to have higher retention rates.
31376333 Risk of Serious Infection Among Initiators of Tumor Necrosis Factor Inhibitors Plus Methot 2020 Oct OBJECTIVE: To compare the risk of serious infections between the use of tumor necrosis factor inhibitors (TNFi) plus methotrexate (MTX) versus triple therapy among rheumatoid arthritis (RA) patients in a real-world setting. METHODS: Using claims data from Truven MarketScan (2003-2014), we conducted a cohort study to compare RA patients receiving MTX who added a TNFi (TNFi plus MTX group) versus MTX plus hydroxychloroquine and sulfasalazine (triple therapy group). The primary outcome was any serious infection (i.e., a composite end point of hospitalized bacterial and opportunistic infections or herpes zoster). Secondary outcomes were individual components of the composite end point. To adjust for baseline confounding, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated the hazard ratio (HR) and 95% confidence interval (95% CI) of the outcomes. RESULTS: After PS stratification (PSS) and weighting, we included a total of 45,208 TNFi plus MTX initiators and 1,387 triple therapy initiators. Mean age was 53 years and 70% were female. The incidence rate of any serious infection per 100 person-years was 2.46 in the TNFi plus MTX group and 2.03 in the triple therapy group. The PSS-weighted HR for any serious infection comparing TNFi plus MTX versus triple therapy was 1.23 (95% CI 0.87-1.74). For the secondary outcomes, the PSS-weighted HR was 1.41 (95% CI 0.85-2.34) for bacterial infection and 0.80 (95% CI 0.55-1.18) for herpes zoster. CONCLUSION: In this real-world cohort of RA patients, we noted no substantially different risk of any serious infection, bacterial infection, or herpes zoster after initiating TNFi plus MTX versus triple therapy, although CIs were wide.
32264972 Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk 2020 Apr 7 BACKGROUND: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab. METHODS: In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590). RESULTS: Greater reductions in C-reactive protein (CRP; - 94.0% vs. -24.0%), serum amyloid A (SAA; - 83.2% vs. -17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; - 18.3% vs. 10.5%) and lipoprotein (a) (- 41.0% vs. -2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab. CONCLUSION: Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02332590. Registered on 5 January 2015.
32301430 Comparative efficacy and safety of current therapies for early rheumatoid arthritis: a sys 2020 Sep OBJECTIVES: This systematic literature review (SLR) and network meta-analysis (NMA) was aimed at comparing the relative efficacy and safety of abatacept (ABA) with other currently recommended therapies for patients with early RA. METHODS: An SLR (January 1998 to June 2018) was conducted including MEDLINE®, Embase, and CENTRAL databases, and grey literature. Population was adults with active RA for ≤2 years treated with biologic DMARDs as monotherapy or in combination with conventional DMARDs. A Bayesian NMA was performed using randomised controlled trials (RCTs) and comparisons for ACR50, DAS28 remission, withdrawal due to adverse events and total withdrawal where reported. RESULTS: Ninety publications pertaining to 69 studies (43 RCTs and 26 observational studies) were identified. Twenty-eight RCTs were eligible to be included in the NMA. ABA as monotherapy was similar to the combination of ABA+methotrexate (MTX) for ACR50 (RR: 0.82 [95% CI 0.51-1.35]), and DAS28 remission (RR: 0.69 [95% CI 0.37-1.3]), as well as for withdrawal due to AEs (RR: 2.35 [95% CI 0.69-7.38]) and all-cause withdrawal (RR: 1.73 [95% CI 0.905-3.35]). ABA as monotherapy and ABA+MTX were both comparable to all other therapies for the main efficacy and safety outcomes. Observational study data reported was congruous with the RCT analysis. CONCLUSIONS: The results of this NMA show similar efficacy and safety between ABA (as monotherapy or in combination with MTX) and other biologics in early RA. Further comparison of different treatment options for early RA is warranted as growing research provides evidence for the application of new novel therapies for RA.
32436170 Rheumatoid Nodule Simulating a Parotid Tumor. 2021 Mar Rheumatoid nodules are an extra-articular manifestation of rheumatoid arthritis that are rarely found in the maxillofacial region. A 59-year-old woman with rheumatoid arthritis treated with methotrexate, leflunomide, and tocilizumab, presented with an enlarging mass in the left parotid region. Magnetic resonance imaging (MRI) displayed a lesion compatible with a neoplasm. However, an incisional biopsy showed features consistent with a rheumatoid nodule. The patient was managed conservatively, including cessation of methotrexate and initiation of treatment with hydroxychloroquine. At 15-month follow-up, the lesion had a significant reduction in size. To our knowledge, this is the first case report of a rheumatoid nodule in the parotid region. Although it is a rare manifestation, clinicians should consider this a possible differential diagnosis of parotid masses in patients with a history of rheumatoid arthritis or connective tissue disease.
32252806 Methotrexate and relative risk of dementia amongst patients with rheumatoid arthritis: a m 2020 Apr 6 BACKGROUND: Inflammatory processes have been shown to play a role in dementia. To understand this role, we selected two anti-inflammatory drugs (methotrexate and sulfasalazine) to study their association with dementia risk. METHODS: A retrospective matched case-control study of patients over 50 with rheumatoid arthritis (486 dementia cases and 641 controls) who were identified from electronic health records in the UK, Spain, Denmark and the Netherlands. Conditional logistic regression models were fitted to estimate the risk of dementia. RESULTS: Prior methotrexate use was associated with a lower risk of dementia (OR 0.71, 95% CI 0.52-0.98). Furthermore, methotrexate use with therapy longer than 4 years had the lowest risk of dementia (odds ratio 0.37, 95% CI 0.17-0.79). Sulfasalazine use was not associated with dementia (odds ratio 0.88, 95% CI 0.57-1.37). CONCLUSIONS: Further studies are still required to clarify the relationship between prior methotrexate use and duration as well as biological treatments with dementia risk.
34756311 Systematic review of the impact of drugs on diffuse interstitial lung disease associated w 2021 Nov OBJECTIVE: To review the available evidence on the impact of rheumatoid arthritis (RA) treatments in associated diffuse interstitial lung disease (ILD). METHODS: Systematic review of studies evaluating the impact of pharmacological treatment in patients with RA and ILD. A bibliographic search in MEDLINE, EMBASE and Cochrane, a selection of articles and the methodological quality assessment (FLC 3.0 OSTEBA) and grading of the level of evidence (SING) of the selected articles were performed. RESULTS: 1,720 references were identified in primary search and 7 in manual or indirect. Forty-three articles were included: 7 systematic reviews, 2 randomized clinical trials, 5 cohort studies, 8 case-control studies and 21 case series. Methotrexate (MTX) and leflunomide (LEF) do not increase incidence, complications or mortality due to ILD. Although the results are not uniform, anti-TNF have often had worse outcomes in incidence, progression and mortality due to ILD than MTX, LEF, abatacept (ABA) and rituximab (RTX). The evidence found is scarce for JAK kinase and antifibrotic inhibitors, and controversial for IL-6 inhibitors. CONCLUSIONS: There is no evidence that MTX or LEF worsens the prognosis of patients with AR-EPID. RTX and ABA seem to have better results than other biologicals, such us TNFi, often achieving stabilization and, in some cases, the improvement of ILD in patients with RA.
31858963 Tofacitinib in combination with methotrexate in patients with rheumatoid arthritis: patien 2020 Sep OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR). METHODS: Patients were randomised 4:4:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg, plus background MTX. Patients receiving placebo advanced to tofacitinib at month 3 (non-responders) or month 6 (remaining patients). Mean changes from baseline in PROs, assessed at months 1-24, included Health Assessment Questionnaire-Disability Index, Patient Global Assessment of disease activity (visual analogue scale [VAS]), Patient Assessment of Arthritis Pain (VAS), health-related quality of life (Short Form-36 version 2), Functional Assessment of Chronic Illness Therapy-Fatigue and Medical Outcomes Study-Sleep. RESULTS: Overall, 539/797 (67.6%) patients completed 24 months' treatment. At month 3, tofacitinib-treated patients reported signi cant (p<0.05) mean changes from baseline versus placebo across all PROs, and significantly more patients reported improvements ≥ minimum clinically important differences versus placebo. Improvements in PROs with tofacitinib were sustained to month 24. Following advancement to tofacitinib, placebo-treated patients generally reported changes of similar magnitude to tofacitinib-treated patients. CONCLUSIONS: Patients with RA and MTX-IR receiving tofacitinib 5 or 10 mg BID plus MTX reported significant and clinically meaningful improvements in PROs versus placebo at month 3, which were sustained through 24 months.