Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
31852367 Platelet indices in patients with chronic inflammatory arthritis: a systematic review and 2020 Oct 2 Correlation between platelet indices and chronic inflammatory arthritis (CIA) remains a moot point today. This meta-analysis aimed to evaluate whether platelet (PLT) count, mean platelet volume (MPV) and platelet distribution width (PDW) associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A systematic literature search was performed in PubMed, EMBASE, and Web of Science up to August 2019. Pooled standardized mean differences (SMD) and 95% confidence interval (CI) were calculated using a random-effect model. As a result, 34 studies were included, encompassing 17 on RA, 12 on AS, 3 on PsA and 2 on both RA and AS. In these studies, PLT count was significantly higher in RA (SMD = 0.55, 95% CI = 0.36-0.73, P < .001), AS (SMD = 0.53, 95% CI = 0.36-0.70, P < .001) and PsA patients (SMD = 1.29, 95% CI = 0.82-1.77, P < .001) than that in healthy subjects, while MPV and PDW presented nonsignificant differences in these intergroup comparisons (P > .05), and similar results were observed in subgroup analyses. The meta-regression analysis demonstrated that there were strong positive correlations between erythrocyte sedimentation rate and PLT count, and weak correlation trend between the disease activity score and PLT count in both RA and AS subjects without statistically significant difference. The sensitivity analysis indicated that these results were not unduly influenced by any single study. In conclusion, this meta-analysis demonstrated that PLT count was elevated in CIA patients and could be suitable for evaluating the disease activity, whereas MPV and PDW were independent of CIA.
32770578 Inhibitory role of long non-coding RNA OIP5-AS1 in rheumatoid arthritis progression throug 2020 Oct NEW FINDINGS: What is the central question of this study? What are the functions of long non-coding (lnc) RNA OIP5-AS1 in development of rheumatoid arthritis inflammation and what is the molecular mechanism? What is the main finding and its importance? LncRNA OIP5-AS1 mitigates rheumatoid arthritis progression through the competitive endogenous RNA network involving the miR-448-paraoxonase 1 axis and through the inactivation of the toll-like receptor 3-nuclear factor κB signalling pathway. This study may offer new ideas for molecularly based control of rheumatoid arthritis. ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long non-coding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1β, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain- and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway.
32216829 Comparative clinical efficacy and safety of the proposed biosimilar ABP 710 with inflixima 2020 Mar 26 BACKGROUND: ABP 710 is being developed as a biosimilar to infliximab reference product (RP). Analytical similarity and pharmacokinetic equivalence between the two have been previously demonstrated. Here we report results from a comparative clinical study that evaluated the efficacy and safety of ABP 710 relative to the RP in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, randomized, double-blind, 50-week equivalence study, patients with moderate to severe active RA despite methotrexate received 3-mg/kg infusions of ABP 710 or RP at predetermined intervals based on initial randomization and then with re-randomization at week 22. The primary endpoint was response difference (RD) of ACR20 at week 22, with clinical equivalence evaluated based on 90% CI of - 15%, 15%. Secondary endpoints included Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP), ACR20, ACR50, and ACR70 across time, as well as safety and immunogenicity assessments. RESULTS: A total of 558 patients were randomized for the initial treatment (ABP 710 n = 279; RP n = 279). The estimated RD of ACR20 at week 22 was 9.37% with 90% CI (2.67%, 15.96%). The lower bound was within the pre-specified criteria, thus confirming non-inferiority; the upper bound exceeded the pre-specified criteria by 0.96% such that superiority could not be ruled out statistically. In a post hoc analysis with adjustment for random imbalance in baseline factors, the CI of RD was narrowed (0.75%, 13.62%). Changes from baseline in DAS28-CRP as well as ACR20, ACR50, and ACR70 response rates across time and hybrid ACR evaluations were similar for the initial and initial/re-randomized treatment groups. Adverse events and incidence of anti-drug antibodies were similar between treatment groups. CONCLUSIONS: These efficacy and safety results support similarity with no clinically meaningful differences between ABP 710 and infliximab RP. Although we were unable to statistically confirm non-superiority, post hoc analysis was supportive of non-superiority. DAS28-CRP, ACR20, ACR50, ACR70, and hybrid ACR evaluations over the entire study were consistently comparable as were safety and immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT02937701. Registered August 30, 2016.
32112272 Screening for acquired latent tuberculosis in rheumatoid arthritis patients on tumor necro 2020 Aug BACKGROUND: There are no studies assessing the development of latent tuberculosis infection (LTBI) in patients on tumor necrosis factor inhibitors (TNFα-I) in high TB prevalence areas of the USA. Our objective was to assess the rate of LTBI development in rheumatoid arthritis (RA) patients on TNFα-I therapies in San Bernardino and Riverside Counties of California, high TB prevalence areas in the US. METHODS: Data were extracted from the electronic health record for 217 adult RA patients across three health centers from January 2010 to January 2017 who have had at least 1 year of TNFα-I use and negative initial QuantiFERON Gold status. Demographics, TNFα-I type, duration of use, TB risk factors, QuantiFERON results, rates of re-screening, TB test seroconversion, and its association with drug use and other factors were assessed. RESULTS: Of the 217 patients, 115 (53%) received baseline and annual screening for LTBI. LTBI was diagnosed in 9.4% (10) of patients. Four patients were on infliximab, three on golimumab, two on adalimumab, and one on etanercept. Hispanic patients tended to have a greater than 200% increase in odds of seroconversion compared to non-Hispanic patients. Infliximab and golimumab were associated with a 92% and 400% increase in odds of seroconversion, respectively. CONCLUSION: The LTBI developed in 9.4% of the patients. This is higher than what is reported for previous US studies. Screening for LTBI in the US should take into consideration TB prevalence, ethnicity, drug type, and duration of use. For our local population and similar populations, annual screening should be practiced. Key Points • Although patients on TNFα inhibitor (TNFα-I) therapy are at high risk of latent tuberculosis infection (LTBI), few studies report the rate of LTBI in patients living in high prevalence areas of the US. • The rate of LTBI was 9.4% in patients on TNFα-I therapy in Southern California. The risk of seroconversion was higher in patients of Hispanic ethnicity and also higher for those on infliximab and golimumab compared to those on other TNFα-I therapies. • Screening guidelines for LTBI screening on TNFα-I should consider local TB prevalence, drugs used, duration of use and ethnicity for cost efficient, and optimal healthcare.
32896703 A systematic review on the effect of DMARDs on fertility in rheumatoid arthritis. 2020 Oct INTRODUCTION: Drug therapy could alter fertility in patients with rheumatoid arthritis (RA). We aimed to perform a systematic review to evaluate if Disease-modifying antirheumatic drug (DMARD) therapy influences fertility as this is an important point to consider in shared decision making on RA therapy. METHODS: A search was conducted at 18/10/2019 in EMBASE, PubMed (including MEDLINE) and the Web of Science Core Collection. Our inclusion criteria were studies involving women or men diagnosed with RA, older than 18 years and on DMARD therapy, with as outcome a fertility parameter. Systematic reviews, meta-analyses, case reports, case series and animal studies were excluded. Studies not in English or Dutch or published before 2004 were excluded. Quality appraisal was performed by the CASP systematic review checklist. RESULTS: After duplicate removal, 9030 references were identified. After title/abstract screening, 82 articles remained. After full text screening, 4 articles could be retained. No studies were found through backward snowballing. Only studies involving women could be retained. The included studies investigated the effect of methotrexate, certolizumab pegol, etanercept and sulfasalazine on fertility. No detrimental effects of these DMARDs on time-to-pregnancy, anti-Müllerian hormone serum level or presence of a history of infertility, were reported. CONCLUSION: This systematic review underlines the gap in knowledge regarding the effect of DMARDs on fertility in women and especially men with RA. DMARD treatment, contrary to general belief, seemed to have no harmful effect on fertility, possibly because it resulted in better controlled disease activity. More research is needed to improve guidance for patients with RA with a child wish.
33307512 Iguratimod inhibits osteoclastogenesis by modulating the RANKL and TNF-α signaling pathwa 2021 Jan BACKGROUND: Iguratimod, a small molecular drug, has been proven to have effective bone protection for treatment of patients with bone loss-related diseases, such as rheumatoid arthritis (RA). However, the exact bone protective mechanism of iguratimod remains to be determined. The purpose of this study was to better explore the underlying mechanism of bone protection of iguratimod. METHODS: Bone marrow monocytes from C57/BL6 mice were stimulated with either RANKL or TNF-α plus M-CSF. The effects of iguratimod on morphology and function of osteoclasts were confirmed by TRAP staining and bone resorption assay, respectively. The expression of osteoclast related genes was detected by RT-PCR and the activation of signal pathway was detected by Western blotting. We used rodent models of osteoporosis (ovariectomy) and of arthritis (modified TNF-α-induced osteoclastogenesis) to evaluate the osteoprotective effect of iguratimod in vivo. RESULTS: Iguratimod potently inhibited osteoclast formation in a dose-dependent manner at the early stage of RANKL-induced osteoclastogenesis, whereas iguratimod had no effect on M-CSF-induced proliferation and RANK expression in bone marrow monocytes. Bone resorption was significantly reduced by both early and late addition of iguratimod. Administration of iguratimod prevented bone loss in ovariectomized mice. The blockage of osteoclastogenesis elicited by iguratimod results from abrogation of the p38、ERK and NF-κB pathways induced by RANKL. Importantly, Iguratimod also dampened TNF-α-induced osteoclastogenesis in vitro and attenuated osteoclasts generation in vivo through disrupting NF-κB late nuclear translocation without interfering with IκBα degradation. CONCLUSIONS: Iguratimod not only suppresses osteoclastogenesis by interfering with RANKL and TNF-α signals, but also inhibits the bone resorption of mature osteoclasts. These results provided promising evidence for the therapeutic application of iguratimod as a unique treatment option against RA and especially in prevention of bone loss.
32420693 Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands 2020 Sep OBJECTIVE: To assess differences between lymphatic function in the affected hands of rheumatoid arthritis (RA) patients with active synovitis and that of healthy controls, using indocyanine green (ICG) dye and near-infrared (NIR) imaging. METHODS: NIR imaging of the hands of 8 patients with active RA and 13 healthy controls was performed following web space injection of 0.1 ml of 100 μM ICG. The percentage of ICG retention in the web spaces was determined by NIR imaging at baseline and at 7 days (±1 day) after the initial injections; image analysis provided contraction frequency. ICG+ lymphatic vessel (LV) length and branching architecture were assessed. RESULTS: Retention of ICG in RA hands was higher compared to controls (P < 0.01). The average contraction frequency of ICG+ LVs in RA patients and in controls did not differ (mean ± SD 0.53 ± 0.39 contractions/minute versus 0.51 ± 0.35 contractions/minute). Total ICG+ LV length in RA hands was lower compared to healthy controls (58.3 ± 15.0 cm versus 71.4 ± 16.1 cm; P < 0.001), concomitant with a decrease in the number of ICG+ basilic LVs in the hands of RA patients (P < 0.05). CONCLUSION: Lymphatic drainage in the hands of RA patients with active disease was reduced compared to controls. This reduction was associated with a decrease in total length of ICG+ LVs on the dorsal surface of the hands, which continued to contract at a similar rate to that observed in controls. These findings provide a plausible mechanism for exacerbation of synovitis and joint damage, specifically the accumulation and retention of inflammatory cells and catabolic factors in RA joints due to impaired efferent lymphatic flow. NIR/ICG imaging of RA hands is feasible and warrants formal investigation as a primary outcome measure for arthritis disease severity and/or persistence in future clinical trials.
31993940 Immune dysregulation syndrome with de novo CTLA4 germline mutation responsive to abatacept 2020 Jun Regulatory T-cells (Tregs) are major mediators of mammalian self-tolerance via cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling pathways. An immune dysregulation syndrome associated with heterozygous germline mutations in CTLA4 was recently reported. Clinical features include recurrent infections, systemic lymphadenopathy, various autoimmune conditions, hypogammaglobulinemia, and autosomal dominant inheritance, characteristic of primary immunodeficient disease (PID). PID symptoms are variable and few patients with sporadic de novo CTLA4 germline mutations have been described. Here, we report the case of a 26-year-old man with an immune dysregulation syndrome and a de novo CTLA4 germline mutation. The patient exhibited several clinical features associated with PID. Next-generation sequencing revealed a CTLA4 germline mutation, c.436G>A; p.G146R, in exon 2 of CTLA4. Sanger sequencing confirmed the patient was the only member of his family with this germline mutation. The patient was diagnosed with an immune dysregulation syndrome associated with de novo germline CTLA4 mutation, complicated by steroid-refractory rheumatoid arthritis. Treatment with abatacept, a CTLA4-immunoglobulin fusion molecule, was initiated, resulting in dramatic resolution of the patient's clinical symptoms. As PID with CTLA4 germline mutation is rare and patients may be under-diagnosed, physicians should be aware of the features of PID.
31492436 Descriptive epidemiology of hip and knee replacement in rheumatoid arthritis: An analysis 2020 Apr OBJECTIVE: To provide descriptive data on rates of total hip replacement (THR) and total knee replacement (TKR) within a large RA cohort and describe variation in risk. METHODS: Incident RA patients (1995 to 2014) were identified from the Clinical Practice Research Datalink (CPRD). First subsequent occurrence of THR and TKR were identified (analysed separately) and incidence rates calculated, stratified by sex, age, BMI, geographic region, and quintiles of the index of multiple deprivation (IMD) score. RESULTS: There were 27,607 RA patients included, with a total of 1,028 THRs (mean age at surgery: 68.4 years) and 1,366 TKRs (mean age at surgery: 67.6 years), at an overall incidence rate per 1,000 person-years (PYs) [95% CI] of 6.38 [6.00-6.78] and 8.57 [8.12-9.04], respectively. TKR incidence was similar by gender but THR rates were higher in females than males. Rates of TKR but not THR rose according to BMI. An increasing trend was observed in rates of both outcomes according to age (although not ≥75) but of decreasing rates according to socio-economic deprivation. There was some evidence for regional variation in TKR. The 10-year cumulative incidence was 5.2% [4.9, 5.6] and 7.0% [6.6, 7.4] for THR and TKR, respectively. CONCLUSION: We provide generalizable estimates of THR and TKR incidence in the UK RA patient population and note variation across several key variables. Increased BMI was associated with a large increase in TKR but not THR incidence. Increased deprivation was associated with a downward trend in rates of THR and TKR.
33040072 Diaphragmatic Lipoma in a Woman with Rheumatoid Arthritis: A Case Report and Literature Re 2020 Oct 11 BACKGROUND A lipoma is a benign tumor made of fat tissue. Diaphragmatic lipomas are frequently reported in case studies. CASE REPORT This study presents a case of diaphragmatic lipoma in a woman with rheumatoid arthritis who was complaining of shortness of breath. A literature review of previously reported diaphragmatic lipoma cases was also carried out. In our patient, normal vital signs were detected, and laboratory results showed that antinuclear antibody, complete blood count, erythrocyte sedimentation rate, and C-reactive protein levels were high. A high-resolution CT scan showed pulmonary nodules and an incidentally found diaphragmatic lipoma. The patient was prescribed corticosteroids, methotrexate, folic acid, and chloroquine. The 3-month follow-up visit revealed symptomatic improvements in breathing difficulties and joint attacks. CONCLUSIONS Diaphragmatic lipoma should be identified to avoid misdiagnosis. Most cases of lipoma require observation. Surgical treatment is indicated only if the mass is symptomatic, increasing in size, or of uncertain nature.
33164399 [Clinical practice guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in 2020 Sep Tripterygium wilfordii Hook.f.(TwHF) is one of the most effective traditional Chinese herbal medicines against rheumatoid arthritis. As the representative agents of TwHF, Tripterygium Glycoside Tablets(TGT) and Tripterygium wilfordii Tablets(TWT) were included as Class A drugs in the 2019 edition of Medicine Catalogue for National Basic Medical Insurance, Injury Insurance and Maternity Insurance, and TGT was also included in 2018 edition of National Essential Drug List and 2015 edition of Chinese Pharmacopoeia. However, it is difficult to grasp the specific clinical applications of TGT and TWT. Side effects occur from time to time. The curative effect is uneven in patients. And the package inserts of TGT and TWT are not described in details. In order to standardize the clinical application of Tripterygium wilfordii preparations, 38 authoritative units and 48 well-known experts in rheumatoid immunology clinical department, drug supervision and management, pharmacy and evidence-based medicine research fields jointly developed Tripterygium Glycoside Tablets and Tripterygium wilfordii Tablets Medication Guide for reference in clinical application, teaching and scientific research. The guideline followed the "evidence-based, consensus-assisted and experience-based" principles to form "recommendations" for the evidence supported ones, and form "consensus suggestions" for those without evidence support by using nominal group method. In this way, the medication recommendations on function, usage and dosage, drug combinations, precautions, efficacy, safety and other aspects of TGT and TWT can be provided. The application of this Guide will help to avoid or reduce the adverse reactions of T. wilfordii preparations, enhance the efficacy and reduce the cost of medicine, with certain demonstration and promotion values to improve the rational use level of traditional Chinese medicine.
31781981 Analysis of lncRNA expression profiles by sequencing reveals that lnc-AL928768.3 and lnc-A 2020 Apr BACKGROUND: This study aimed to analyze long non-coding RNA (lncRNA) expression profiles in synovium tissue of patients with RA using RNA sequencing, and to further assess the clinical values of dysregulated lncRNAs in RA diagnosis and monitoring. METHODS: Thirty patients with RA who underwent knee arthroscopy and 30 controls with knee trauma who underwent surgery were consecutively enrolled and synovium tissue samples of both groups were obtained during surgery. In the exploration stage, lncRNA and mRNA expression profiles in three RA samples and three control samples were detected by RNA sequencing and bioinformatic analyses were then performed. In the validation stage, quantitative polymerase chain reaction (qPCR) was subsequently used to detect expression of five candidate lncRNAs in 30 patients with RA and 30 control patients. RESULTS: A total of 349 lncRNAs and 1582 mRNAs were upregulated and 806 lncRNAs and 1295 mRNAs were downregulated in patients with RA compared with controls. Enrichment analyses revealed that these dysregulated lncRNAs and mRNAs were mainly involved in regulating immune response, leukocyte migration, complement activation, and B cell receptor signaling pathway. Subsequent qPCR validation discovered that lnc-AL928768.3 (P < 0.001) and lnc-AC091493.1 (P < 0.001) were elevated in patients with RA compared with controls and afford good predictive values for RA risk by receiver operating characteristic (ROC) curve analysis. Additionally, the two lncRNAs were positively associated with C-reactive protein level and disease activity score in 28 joints (ESR) (all P < 0.05). CONCLUSION: Analysis of lncRNA expression profiles by sequencing reveals that lnc-AL928768.3 and lnc-AC091493.1 are novel biomarkers for RA risk and activity.
32964675 Obesity-Related Traits and the Development of Rheumatoid Arthritis: Evidence From Genetic 2021 Feb OBJECTIVE: To investigate the association between obesity-related traits and risk of rheumatoid arthritis (RA). METHODS: We conducted genetic correlation analysis and a 2-sample Mendelian randomization (MR) study, using genome-wide genetic data based on >850,000 individuals of European ancestry. Summary statistics were collected from the largest genome-wide association study conducted to date for body mass index (BMI; n = 806,810), waist-to-hip ratio (WHR; n = 697,734), WHR adjusted for BMI (WHRadjBMI; n = 694,649), and RA (n(case) = 14,361, n(control) = 43,923). We conducted cross-trait linkage disequilibrium score regression and ρ-HESS analyses to quantify genetic correlation between pairs of traits (causal overlap). For each obesity-related exposure, we utilized independent, genome-wide significant single-nucleotide polymorphisms (P < 5 × 10(-9) ) as instruments to perform MR analysis (causal relationship). We interrogated the causal relationship both in the general population and in a sex-specific manner and calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity analyses were performed to validate MR model assumptions. RESULTS: Despite a negligible overall genetic correlation between the 3 obesity-related traits and RA, we found significant local genetic correlations at several regions on chromosome 6 (positions 28-29M, 30-35M, and 50-52M), highlighting a shared genetic basis. We further observed an increased risk of RA per SD increment (4.8 kg/m(2) ) in genetically predicted BMI (OR 1.22 [95% CI 1.09-1.37]). The effect was consistent across sensitivity analyses and comparable between sexes (OR 1.22 [95% CI 1.04-1.44] in male subjects and 1.19 [95% CI 1.04-1.36] in female subjects). However, we did not find evidence supporting a causal role of either WHR (OR 0.98 [95% CI 0.84-1.14]) or WHRadjBMI (OR 0.90 [95% CI 0.79-1.04]) in RA. CONCLUSION: Genetically predicted BMI significantly increases RA risk. Future studies are needed to understand the biologic mechanisms underlying this link.
33186593 Traditional and modern management strategies for rheumatoid arthritis. 2021 Jan Rheumatoid arthritis (RA) is a serious disorder of the joints affecting 1 or 2% of the population aged between 20 and 50 years worldwide. RA is the foremost cause of disability in developing and Western populations. It is an autoimmune disease-causing inflammation and pain involving synovial joints. Pro-inflammatory markers, including cytokines, such as interleukin -1 (IL-1), IL-6, IL-7, IL-8, and tumor necrosis factor-α (TNF-α) are involved in RA. RA treatment involves TNF-α blockade, B cell therapy, IL-1 and IL-6 blockade, and angiogenesis inhibition. Synthetic drugs available for the treatment of RA include disease-modifying anti-rheumatic drugs (DMARD), such as cyclophosphamide, sulfasalazine, methotrexate, nonsteroidal anti-inflammatory drugs (NSAIDs), and intramuscular gold. These agents induce adverse hepatorenal effects, hypertension, and gastric ulcers. We found that patients diagnosed with chronic pain, as in RA, and those refractory to contemporary management are most likely to seek traditional medicine. Approximately 60-90% of patients with arthritis use traditional medicines. Therefore, the efficacy and safety of these traditional medicines need to be established. The treatment for RA entails a comprehensive multidisciplinary strategy to reduce pain and inflammation and to restore the activity of joints. The potential medicinal plants exhibiting anti-arthritic and anti-rheumatic pharmacological activity are reviewed here.
32929677 Cost-Effectiveness of Tofacitinib for Patients with Moderate-to-Severe Rheumatoid Arthriti 2020 Dec BACKGROUND: Patients with moderate-to-severe rheumatoid arthritis have a heavy financial burden. The cost-effectiveness of introducing tofacitinib to the current treatment sequence for patients with moderate-to-severe rheumatoid arthritis who have inadequate response or intolerance to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs-IR) in China remains unknown. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of introducing tofacitinib into the current treatment sequence in China for patients with moderate-to-severe rheumatoid arthritis who have csDMARDs-IR. METHODS: A Markov model was constructed from the perspective of the Chinese healthcare system to compare treatment sequences with and without first-line tofacitinib for patients with rheumatoid arthritis with csDMARDs-IR. The treatment sequence without tofacitinib included adalimumab, etanercept, recombinant human tumor necrosis factor receptor-Fc fusion protein, infliximab, and tocilizumab. Costs were derived from publicly available sources. Clinical trials, network meta-analysis, and real-world data were used to generate quality-adjusted life-years (QALYs), transition probabilities, and the incidence of adverse events. Mortality probabilities were estimated from rheumatoid arthritis-based, Chinese all-cause mortality data. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. In addition, the cost-effectiveness of adding tofacitinib as second- and third-line treatment options was evaluated in our analyses. Costs and effects were discounted at 5% per anum. RESULTS: Compared to the current treatment sequence, adding tofacitinib as first-line treatment led to a cost-saving of $US880.11 (2018 values) and incremental QALYs of 1.34. Sensitivity analyses showed the results to be robust. Adding tofacitinib at second-line therapy was also a cost-saving option with a cost saving of $US653.65 and incremental QALYs of 1.34, while the incremental cost-effectiveness ratio of adding tofacitinib at third-line therapy was $US5588.14 per QALY gained. CONCLUSIONS: Using the WHO-recommended ICER acceptability threshold of ≤ 1-time per capita Gross Domestic Product (GDP), our analysis suggests that the introduction of tofacitinib into the current treatment sequence for moderate-to-severe RA patients with csDMARDs-IR in China was a cost saving option as first- and second-line treatment, and cost-effective as a third-line treatment option. Of note, use of tofacitinib as first- and second-line treatment post-csDMARDs-IR appeared to be cost saving.
32206973 Sustained improvement in work outcomes in employed patients with rheumatoid arthritis duri 2020 Sep OBJECTIVE: The goal of this study was to evaluate the long-term impact of adalimumab therapy on work-related outcomes in employed patients with rheumatoid arthritis (RA). METHOD: We utilized data from an observational cohort of German patients who initiated adalimumab treatment during routine clinical care. Analyses were based on employed patients (part-time or full-time) who continued adalimumab treatment for 24 months. Major outcomes were self-reported sick leave days in the previous 6 months, absenteeism, presenteeism, and total work productivity impairment as assessed by the Work Productivity and Activity Impairment (WPAI) questionnaire and disease activity assessments. The normal number of sick leave days was based on data from the German Federal Statistical Office. RESULTS: Of 783 patients, 72.3% were women, mean age was 47.9 years, and mean disease duration was 7.8 years. At baseline (before adalimumab initiation), 42.9% of patients had higher than normal sick leave days (> 5) in the previous 6 months. During 24 months of adalimumab treatment, 61% of patients with higher than normal sick leave days at baseline returned to normal sick leave values (≤ 5 days/6 months). Overall, mean sick leave days/6 months decreased from 14.8 days at baseline to 7.4 days at month 24. Improvements were observed in WPAI assessments and disease activity measures, although presenteeism levels remained high (32.2% at month 24). CONCLUSIONS: Adalimumab treatment was associated with strong and sustained improvements in work-related outcomes in employed patients who continued on adalimumab for 24 months. Presenteeism appears to be the work outcome most resistant to improvement during RA treatment. TRIAL REGISTRATION: NCT01076205 Key Points • Long-term adalimumab therapy was associated with sustained improvements in work outcomes in patients with rheumatoid arthritis. • Despite improvements in sick leave days and work absenteeism, presenteeism (impairment while at work) remained relatively high.
32094157 Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a co 2020 Apr OBJECTIVES: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target. METHODS: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models. RESULTS: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52). CONCLUSION: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.
32681420 Selectivity of Janus Kinase Inhibitors in Rheumatoid Arthritis and Other Immune-Mediated I 2020 Aug Janus kinase (JAK) is a signal transducer and activator of a protein transcription system that transduces signals from cell surface cytokine and growth factor receptors to the nucleus. Recently developed JAK inhibitors (JAKinibs) inhibit JAKs non-selectively or selectively and down-regulate the effects of corresponding ligands (i.e. cytokines and growth factors). JAKinibs are efficacious against rheumatoid arthritis and other immune-mediated inflammatory diseases and are being increasingly prescribed clinically. Regarding safety, JAKinib use is associated with common or unique changes in laboratory parameters; however, incidence rates of serious adverse drug reactions (ADRs) associated with these changes are low. Opportunistic and other infections, including tuberculosis, are the most critical ADRs of treatment with JAKinibs, and screening and monitoring of patients should be carefully performed. Incidence rates of herpes zoster (HZ) in patients receiving JAKinibs are high in Japan and Korea, and modestly high in other countries. Filgotinib may not be associated with an elevated risk for HZ, but long-term safety data are lacking. Data from clinical development programmes and post-marketing surveillance have indicated no increased risk for malignancy or serious cardiac events; however, long-term observational studies are necessary. Despite the non-elevated risk of gastrointestinal perforations, patients with older age and/or a history of diverticulitis or receiving non-steroidal anti-inflammatory drugs should be carefully evaluated to determine the risk-benefit balance. The incidence rates of venous thromboembolism with all approved doses are similar to that expected in the population, although there are discrepancies in the placebo-controlled portion of the baricitinib clinical development programmes. Regulatory agencies in the USA and Europe suggested a higher risk for thrombotic events in patients receiving JAKinibs. Pharmacokinetic studies demonstrated that dose adjustment should be considered for JAKinib use in patients with moderate-to-severe renal or hepatic dysfunction, depending on the metabolism of each drug. Long-term observational studies enrolling patients with diverse clinical backgrounds are required to strike a risk-benefit balance in clinical settings.
30385295 Practical Aspects of Biological Throught Levels and Antidrug Antibodies in Rheumatoid Arth 2020 Sep OBJECTIVES: Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. METHODS: We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. RESULTS: It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). CONCLUSIONS: Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making.
32615835 Patient characteristics affecting knowledge of the possibility of surgical reconstruction 2021 May OBJECTIVES: We aimed to investigate patient characteristics affecting their knowledge of surgical reconstruction for rheumatoid hand and wrist deformities, and to investigate such characteristics affecting their hope of receiving hand surgery if patients with rheumatoid arthritis (RA) knew surgical reconstruction options. METHODS: We carried out a questionnaire survey for all patients with RA who came to our outpatient department of rheumatology. Multivariate logistic regression analysis was performed to examine significant characteristics associated with the knowledge of surgical reconstruction and patients' hope of receiving hand surgery. RESULTS: In total, 687 patients were evaluated in this study and 337 (49%) reported knowledge about surgical reconstruction. A multivariate logistic regression analysis showed that patients with good control of disease activity and with long-lasting hand and wrist deformities were significantly associated with having knowledge of surgical reconstruction. Among the 337 patients with knowledge, only 122 (36%) expressed a hope of receiving hand surgery. The statistical analysis showed that younger age and surgical history were significantly associated with the hope of receiving surgery. CONCLUSION: Surgeons and rheumatologists should enlighten patients about the importance of hand surgery to achieve functional remission in this new era of treatment for patients with RA.