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ID PMID Title PublicationDate abstract
31573475 Clinical features and current treatments of adult-onset Still's disease: a multicentre sur 2019 Nov OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30
31383831 Adult-onset Still's Disease as a Differential Diagnosis in Prolonged Fever: Diagnosis and 2019 Apr Adult onset Still's disease is a rare systemic disease that may involve many organs and may mimick many disease such as infection, autoimmune disease, and also malignancy. The diagnostic approach and treatment strategies have not been well established due to its rarity; however, there are some diagnostic criteria that may help. We present a case of 36-year old man who experienced high prolonged fever which firstly thought as infection. He also had unilateral wrist and knee joint pain and maculopapular rash. Laboratory examination showed high leukocytes count with elevated polymorphonuclear neutrophil count, high platelet count, high ferritin level, and negative results of many infection markers (typhoid antibody, procalcitonin, malaria test, blood culture, urine culture, IgM pneumonia, ASTO, syphilis test, antiHIV, HBsAg, antiHCV, etc). Chest X-ray, joint X-ray, ultrasonography, and echocardiography showed normal result. The patient was then diagnosed with Adult-onset Still's disease and received intravenous methylprednisolone and the fever was disappeared in 3 days. Six months later the arthralgia appeared again, methotrexate was administered and the pain was then relieved.
31660534 A systematic review of guidelines for managing rheumatoid arthritis. 2019 BACKGROUND: We systematically reviewed current guidelines for managing rheumatoid arthritis (RA) to evaluate their range and nature, assess variations in their recommendations and highlight divergence in their perspectives. METHODS: We searched Medline and Embase databases using the terms 'clinical practice guidelines' and 'rheumatoid arthritis' from January 2000 to January 2017 together with publications of national and international bodies. We included guidelines providing recommendations on general RA management spanning a range of treatments and published in English. We undertook narrative assessments due to the heterogeneity of the guidelines. RESULTS: We identified 529 articles; 22 met our inclusion criteria. They were primarily developed by rheumatologists with variable involvement of patient and other experts. Three dealt with early RA, one established RA and 18 all patients. Most guidelines recommend regular assessments based on the Outcome Measures in Rheumatology core dataset; 18 recommended the disease activity score for 28 joints. Twenty recommended targeting remission; 16 suggested low disease activity as alternative. All guidelines recommend treating active RA; 13 made recommendations for moderate disease. The 21 guidelines considering early RA all recommended starting disease modifying drugs (DMARDs) as soon as possible; methotrexate was recommended for most patients. Nineteen recommended combination DMARDs when patients failed to respond fully to monotherapy and biologics were not necessarily indicated. Twenty made recommendations about biologics invariably suggesting their use after failing conventional DMARDs, particularly methotrexate. Most did not make specific recommendations about using one class of biologics preferentially. Eight recommended tapering biologics when patients achieved sustained good responses. CONCLUSIONS: Five general principles transcend most guidelines: DMARDs should be started as soon as possible after the diagnosis; methotrexate is the best initial treatment; disease activity should be regularly monitored; give biologics to patients with persistently active disease who have already received methotrexate; remission or low disease activity are the preferred treatment target.
30679969 Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases. 2019 Feb The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.
31709258 Methotrexate-Associated Pneumonitis and Rheumatoid Arthritis-Interstitial Lung Disease: Cu 2019 Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects ~1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors, and treatment options in RA-ILD and M-pneu. M-pneu, usually has an acute/subacute course characterized by cough, dyspnea and fever. Several risk factors, including genetic and environmental factors have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with non-specific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires immediate cessation of MTX and commencement of glucocorticoids. RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-citrullinated peptide antibodies and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.
30937478 [Adult-onset Still's disease : Rare adult-onset autoinflammatory syndrome]. 2019 Jul Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by high spiking fever, arthritis, salmon-pink maculopapular rash and multiple organ involvement. We report a case of an adult-onset Still's disease that meets Yamaguchi's criteria and presented with typical clinical manifestations. AOSD is treated with anti-inflammatory medications. Standard therapy includes corticosteroids. Other medications like azathioprine, methotrexate or interleukin-1 or -6 blockers can be used when standard steroid treatment is not adequate.
31005039 Curcumin attenuates collagen-induced rat arthritis via anti-inflammatory and apoptotic eff 2019 Jul Curcumin is a natural herbal product that has been popularly used to treat autoimmune diseases in China; however, its effects on rheumatoid arthritis and its mechanism are not clear. The main purposes of this study are to explore the therapeutic effects of curcumin on collagen-induced arthritis (CIA) rats and the pharmacological mechanism. In the present study, CIA rats were established by injecting bovine type II collagen. Curcumin and methotrexate were then orally administered daily, and the swelling degree of the hind limb joints was scored every two days. Histopathological changes were observed by hematoxylin-eosin staining. The levels of cytokines (TNF-α, IL-1β, IL-17 and TGF-β) were detected by radioimmunoassay, while the expression of IκBα and COX-2 was detected by Western blot. In addition, cell viability was detected by CCK-8 assay, and the effect of curcumin on macrophage apoptosis was detected by flow cytometry and TUNEL assay. The results indicated that in vivo curcumin attenuated the degree of joint swelling of rats and the further development of joint histopathology. Moreover, it downregulated the levels of cytokines. In vitro curcumin inhibited the degradation of IκBα and reduced the production of COX-2 in LPS-induced inflammatory RAW264.7 cells. Importantly, curcumin significantly induced macrophage apoptosis. In conclusion, in this study, we have demonstrated that curcumin exerts therapeutic effects on arthritis in CIA rats and has a strong pharmacological activity on reducing the inflammatory response in macrophages. Its mechanism may be related to the inhibition of the NF-κB signaling pathway and the promotion of macrophage apoptosis.
31474860 Efficacy and Safety of Multiple Dosages of Fostamatinib in Adult Patients With Rheumatoid 2019 Background: Rheumatoid arthritis is a type of systemic and complex autoimmune other disease characterized by chronic joint inflammation. Spleen tyrosine kinase (Syk) inhibitors are regarded as an effective alternative to existing drugs for the treatment of this disease. However, studies evaluating fostamatinib, a new Syk inhibitor, are either invalid or insufficient. Through a systematic review and meta-analysis, we evaluated the efficacy and safety of fostamatinib at different dosages in rheumatoid arthritis patients that display an inadequate response to methotrexate or disease-modifying antirheumatic drugs. Methods: Randomized controlled trials published between January 2000 and November 2018 were retrieved from PubMed, Embase, Medline, Web of Science, and The Cochrane Library. We also searched a relevant website (www.clinicaltrials.gov) for retrieval of unpublished data. These studies compared different dosages of fostamatinib to placebo, including the intake of 100 mg fostamatinib twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) vs. the intake of 100 mg bid. Results: Two investigators analyzed 11 randomized placebo-controlled trials consisting of 3,680 patients. Compared to placebo, fostamatinib resulted in an obvious reduction in the American College of Rheumatology 20% response standard [weighted mean difference (WMD) 1.96, 95% confidence interval (CI) [1.46, 2.61], P < 0.001] and disease activity score < 2.6 (WMD 4.70, 95% CI [3.14, 7.03], P < 0.001). Regarding safety, the incidence of serious adverse reactions was higher in the fostamatinib group than in the placebo group [risk ratio (RR) 2.10, 95% CI [1.57, 2.80], P < 0.001]. The same was true for other adverse events [RR 1.63, 95%CI [1.33, 2.01], P < 0.001]. Conclusions: Fostamatinib is an effective and safe therapeutic medicine administered to patients with rheumatoid arthritis over 24 weeks. It can alleviate the degree of swelling and inflammation of the joints. Furthermore, 100 mg bid can be considered the most beneficial regimen over a 24-week period. More data are however needed to clarify the incidence of other adverse events and serious adverse reactions.
31028049 Complex presentation of adult-onset Still's disease. 2019 Apr 25 A 61-year-old woman was admitted with feeling generally unwell with influenza-like symptoms, for almost a month. This was followed by dyspnoea, productive cough and fever of >40°C. She was started on oral antibiotics in community, but due to rising inflammatory markers, she was referred for admission to our hospital. Chest X-ray showed left basal pneumonia and SE was started on intravenous antibiotics according to microbiologist's advice. During admission she developed deranged liver functions with right upper quadrant tenderness, pleural and pericardial effusions. This was followed by multiple joint aches, mouth ulcers and a rash on her chest. Finally, after several days and clinical dilemma, she was diagnosed with adult-onset Still's disease by the rheumatologist and was started on prednisolone, to which she showed marked improvement, and was later maintained on methotrexate and hydrotherapy. She was in remission during her follow-up in the rheumatology clinic.
31698794 Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of 2019 Nov 6 Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.
31749869 Modulator role of infliximab and methotrexate through the transient receptor potential mel 2019 Oct INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients. MATERIAL AND METHODS: Neutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA). RESULTS: Intracellular free Ca(2+) concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca(2+) concentrations were further decreased by the ACA therapy. CONCLUSIONS: Our results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca(2+) concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.
31110572 Values and Correlations between C-Reactive Protein and Apolipoprotein B after Treatment wi 2019 Apr 30 BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). Lipid changes related to inflammation have been described in RA. Methotrexate (MTX) treatment is effective in controlling inflammation and decreasing the CRP (C-reactive protein) values. AIM: To examine the disease activity, CRP and Apo B values in the detection of new patients with active and untreated RA, and impact of MTX therapy on their levels after 6 months and one year of treatment, and the correlation between their values in this period. METHODS: 80 patients with active and newly discovered RA patients who meet the American Rheumatology Association (ARA) 1987 revised criteria were treated with disease-modifying anti-inflammatory drugs (DMARDs) according to the protocol for treatment. RESULTS: After a year of therapy RA patients achieved significant decrease in the DAS28 (disease activity score) (p < 0.01 and p < 0.001), and CRP values (p < 0.001). Levels of Apo B values at the 12 months were nonsignificantly higher compared to the results obtained at the beginning of the study (p < 0.001). After 6 and 12 months there was a weak nonsignificant negative correlation about the values of CRP and Apo B at baseline and after 12 months (r = -0.15 and r = -0.12 p > 0.05). CONCLUSION: Use of MTX therapy at RA patients had a reduced effect on disease activity and inflammation, but the nonsignificance effect on the values of Apo B lipoproteins.
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.
31707603 Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors a 2019 Nov 9 INTRODUCTION: No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. METHODS: This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. RESULTS: Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. CONCLUSIONS: In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. FUNDING: Pfizer Inc.
31333447 Anti-Inflammatory and Anti-Arthritic Efficacies of an Indian Traditional Herbo-Mineral Med 2019 Rheumatoid arthritis (RA) is defined as a chronic autoimmune inflammatory disorder that causes damage to limb joints and progressive injuries to secondary organs. Medical practitioners prescribe Methotrexate (MTX) as standard care medicine for treating RA. However, the long-term application of MTX has shown to have adverse health-related effects. Divya Amvatari Ras (DAR), an Indian Ayurvedic herbo-mineral formulation, has been described in ancient texts to provide relief from RA inflammation associated distress. Therefore, in the present study, we explored the biocompatibility, anti-inflammatory, and anti-arthritic efficacy of DAR using in vivo and in vitro disease models. Using carrageenan (CA)-stimulated Wistar rat paw edema model, we showed a reduction in inflammation-induced paw edema at human equivalent dose of DAR. Anti-rheumatic efficacy of DAR was studied using collagen-antibody cocktail (C-Ab) Induced Arthritis (CAIA) mouse model. The onset of RA in the CAIA mice was determined using parameters such as the increase in arthritis score, and induction of disease associated lesions in the ankle and knee joints, and increase in mechanical and thermal hyperalgesia. Treatment of CAIA animals with a human equivalent dose of DAR significantly reversed the RA-associated pathogenesis. These effects were comparable with the standard of care RA drug, MTX. DAR acted at multiple levels of inflammation associated with RA to reduce progressive pathogenesis. Animal serum biochemistry showed DAR was capable of ameliorating RA induced increase in liver enzyme Alanine Aminotransferase (ALT) and pro-inflammatory cytokine interleukin 6 (IL-6). In the lipopolysaccharide stimulated THP-1 cells, DAR was found to inhibit the release of IL-6, IL-1β, TNF-α, and upstream inflammatory gene regulatory protein, NFκB. The study endorsed the anti-arthritic and anti-inflammatory activity of the Indian Traditional herbo-mineral medicine, DAR. These results also confirm that DAR was highly biocompatible and would show minimal health-related side effects than those associated with standard of care MTX. Taken together, we show that the DAR could be utilized as a promising alternative or complementary therapy for treating rheumatoid arthritis.
31742964 2019 Sep The objective of the current review is to perform a systematic review of the beneficial and harmful effects of baricitinib 2 mg orally once daily in combination with methotrexate(MTX) (or as monotherapy in cases of intolerance to MTX) for the treatment of adult patients with moderate-to-severe rheumatoid arthritis who have responded inadequately to one or more disease-modifying antirheumatic drugs.
31385264 Patient Perceptions of Unmet Medical Need in Rheumatoid Arthritis: A Cross-Sectional Surve 2019 Sep INTRODUCTION: Many rheumatoid arthritis (RA) patients do not achieve their treatment goals and experience symptoms that affect psychosocial outcomes and daily activities. This study aimed to identify and quantify the unmet needs perceived by US patients with RA currently taking a disease-modifying antirheumatic drug (DMARD). METHODS: A cross-sectional, web-based survey was conducted with RA patients recruited through CreakyJoints, an online patient support community, and ArthritisPower(®), an online patient research registry, from December 2017 to January 2018. Participant patients were aged ≥ 21 years, failed ≥ 1 DMARDs, and were receiving their current DMARD(s) for ≥ 6 months; they answered 50 questions about treatment history, RA symptoms, and flares and completed the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Treatment Satisfaction Questionnaire for Medication (TSQM). Treatment satisfaction was defined by a TSQM global satisfaction score ≥ 80. RESULTS: Of 415 patients screened, 258 (62%) were eligible and completed the survey; 87% were women, and 87% white, with mean (SD) age of 54.5 (11.4) years. A total of 232 patients (90%) had current or past biologic DMARD (bDMARD) use, with 67% currently on a bDMARD, 65% on ≥ 1 conventional synthetic DMARD, and 40% on methotrexate. Forty-three percent of patients reported daily/almost daily use of prescription pain medications, and 44% reported a current flare. Mean (SD) TSQM scores were 59 [20] for effectiveness, 59 [26] for side effects, 72 [18] for convenience, and 65 [21] for global satisfaction. The mean (SD) RAID overall score was 5.1 (2.0) on a 0-10 scale. Only 26% (67 patients) were satisfied with their RA treatment. Patients not satisfied with treatment reported higher RAID scores overall and by domain, and approximately half reported a current flare. CONCLUSIONS: Results from this real-world survey suggest that three-fourths of RA patients are not satisfied with treatments, which include bDMARDs. Patients continued to experience bothersome symptoms that impacted their daily activities and life. There remains a need for improved disease management among currently treated RA patients. FUNDING: Eli Lilly and Company (Indianapolis, IN, USA).
30858625 SLC22A5 polymorphism associated with risk of extra-articular manifestations in rheumatoid 2019 OBJECTIVES: Rheumatoid arthritis (RA), the most common autoimmune disease, is thought to be a complex disease in which a combination of risk alleles from different susceptibility genes predisposes to development of the disease, following exposure to as yet unknown environmental factors. An important component of the carnitine system is the plasma membrane carnitine transporters, also called organic cation transporters, i.e. OCTN1 and OCTN2 encoded by the SLC22A4 and SLC22A5 genes, respectively. The aim of this study was to investigate the association between SLC22A5 polymorphism and RA. MATERIAL AND METHODS: The study was carried out on 404 patients diagnosed with RA according to the criteria of the American College of Rheumatology and 560 healthy subjects. The single nucleotide polymorphism (SNP) within the SLC22A5 gene - 207C>G (rs 2631367) was genotyped using pre-validated TaqMan genotyping assays. RESULTS: The distribution of SLC22A5 genotypes and alleles in RA patients did not differ significantly from that in healthy controls. Moreover, there were no significant associations between SLC22A5 genotypes and age at time of disease diagnosis, rheumatoid factor, erosive disease and response to treatment with methotrexate. Extra-articular manifestations were diagnosed in 16.7% of SLC22A5 GG homozygous patients, in 9.4% with the GC genotype and in 7.2% of homozygous CC patients. The frequency of extra-articular manifestations was two-fold greater in homozygous GG patients as compared with carriers of the C allele (GG vs. GC + CC), OR = 2.06 (95% CI: 1.11-3.85, p = 0.022). CONCLUSIONS: The results of the present study suggest that the SLC22A5 polymorphism may be associated with the development of extra-articular manifestations of RA but the distribution of SLC22A5 genotypes and alleles in studied RA patients did not significantly differ from healthy subjects.
30859494 Tocilizumab Patterns of Use, Effectiveness, and Safety in Patients with Rheumatoid Arthrit 2019 Jun INTRODUCTION: The objective of this study was to observe the patterns of usage, efficacy, and safety of tocilizumab (TCZ) in clinical practice in patients with rheumatoid arthritis. METHODS: Data on the real-world usage, efficacy, and safety of TCZ were collected from patients during routine follow-up visits conducted over a 6-month period. Patients were grouped by previous exposure to biologic therapies (biologic exposed vs. biologic naive). RESULTS: Of 1912 patients enrolled from 16 countries, 639 (33.4%) received TCZ monotherapy and 1273 (66.6%) received TCZ combination therapy. At baseline, 1073 patients (56.1%) were biologic naive and 839 (43.9%) were biologic exposed. At 6 months, 1504 patients (78.7%) continued to receive TCZ treatment, with no descriptive differences in retention rates between biologic-exposed and biologic-naive patients and between patients receiving TCZ monotherapy or combination therapy. Dose and use of methotrexate and prednisone were reduced at 6 months. Efficacy at 6 months, including patient-reported outcomes, was demonstrated in both biologic-naive and biologic-exposed groups. Adverse events (AEs) occurred in 817 patients [42.7%; incidence rate: 179 events per 100 patient-years (PY)], and serious AEs (SAEs) occurred in 118 patients (6.2%; 17 events per 100 PY), with comparable rates of AEs and SAEs between subgroups. CONCLUSION: In routine clinical practice, TCZ discontinuation rates were low and unaffected by prior use of biologics. Effectiveness was similar between groups, and no new safety signals were identified. FUNDING: F. Hoffmann-La Roche.
31102087 Concomitant methotrexate has little effect on clinical outcomes of abatacept in rheumatoid 2019 Sep OBJECTIVE: To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. METHODS: A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(-)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. RESULTS: Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(-)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (- 1.35/- 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks. CONCLUSION: In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. KEY POINTS: • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.