Browse

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

ID PMID Title PublicationDate abstract
34600581 Shikonin attenuates rheumatoid arthritis by targeting SOCS1/JAK/STAT signaling pathway of 2021 Oct 2 BACKGROUND: Rheumatoid arthritis is a progressive and systemic autoimmune disease seriously compromises human health. Fibroblast like synoviocytes are the major effectors of proliferation and inflammation in rheumatoid arthritis synovial tissue. Shikonin has anti-inflammatory and immunomodulatory activities. But, its role on synovitis of rheumatoid arthritis is unknown. METHODS: The DBA/1 male mice were randomly divided into the following three groups (n = 6): (1) the normal control group of mice, (2) the CIA (collagen-induced arthritis) group in which mice suffered from arthritis induced by collagen, (3) the SKN (shikonin) group of mice which got arthritis and given intragastrically with shikonin 4 mg/kg per day continuously for 20 days,(4) the MTX (methotrexate) group of mice which got arthritis and orally administration with shikonin 0.5  mg/kg once two days continuously for 20 days. The therapeutic effect of shikonin on collagen induced arthritis mice was tested by arthritis incidence rate, arthritis score and inflammatory joint histopathology. The invasion, adhesion and migration of fibroblast like synoviocytes induced by tumor necrosis factor-α were applied to measure the anti-synovitis role of shikonin. The effect of shikonin on expression of interleukin-6, interleukin-1β and tumor necrosis factor-α was measured by enzyme linked immunosorbent assay. The interaction between shikonin and suppressor of cytokine signaling 1 was verified by molecular docking. The signaling pathways activated by shikonin were measured by western blot. RESULTS: Shikonin decreased the arthritis score and arthritis incidence, and inhibited inflammation of inflamed joints in collagen induced arthritis mice. And shikonin reduced the number of vimentin(+)cells in collagen induced arthritis mice inflamed joints. Meanwhile, shikonin suppressed tumor necrosis factor-α-induced invasion, adhesion and migration of fibroblast like synoviocytes and reduced the expression of interleukin-6, interleukin-1β and tumor necrosis factor-α. And we found that shikonin targeted suppressor of cytokine signaling 1. More interestingly, shikonin blocked the phosphorylation of Janus kinase 1/signal transducer andactivator of transcription 1/signal transducer andactivator of transcription 6 in synovial tissues and in fibroblast like synoviocytes. CONCLUSION: Shikonin represents a promising new anti-rheumatoid arthritis drug candidate that has anti-synovitis effect in collagen induced arthritis mice and inhibits tumor necrosis factor-α-induced fibroblast like synoviocytes by targeting suppressor of cytokine signaling 1/ Janus kinase/signal transducer andactivator of transcription signaling pathway. These findings demonstrate that shikonin has anti-synovitis effect and has great potential to be a new drug for the treatment of rheumatoid arthritis.
34228181 Comparative efficacy and safety of infliximab and its biosimilars in patients with rheumat 2021 Jul 6 OBJECTIVE: To assess the relative efficacy and safety of infliximab and its biosimilars in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs), comparing the efficacy and safety of infliximab biosimilars versus the originator product in patients with active RA despite receiving MTX. RESULTS: Overall, 7 RCTs involving 3168 patients, including 7 biologic agents, met the inclusion criteria. The NI-071 was listed at the top left of the diagonal of the league table because it was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the American College of Rheumatology 20 (ACR20) response rate. SB2 was listed at the bottom right of the diagonal of the league table because it was associated with the least favorable results. Based on SUCRA, NI-071 had the highest probability of being the best treatment agent in terms of the ACR20 response rate (SUCRA = 0.731), followed by ABP 710, CT-P13, BCD-055, infliximab, Exemptia, PF-06438179, and SB2 (SUCRA = 0.311). Although statistically non-significant differences in safety ranking were observed for serious adverse events (SAEs) among the treatment options, ABP 710 presented the highest safety probability (SUCRA = 0.739) while BCD-055 showed the lowest safety profile (SUCRA = 0.289). CONCLUSION: No significant difference in ACR20 response rates and SAEs were detected between infliximab biosimilars and the originator in the investigated study populations.
33999266 Comparative efficacy and safety of adalimumab biosimilars and adalimumab in patients with 2021 May 17 OBJECTIVE: We assessed the relative efficacy and safety of adalimumab and biosimilars in patients with active rheumatoid arthritis (RA) presenting an inadequate response to methotrexate (MTX). METHODS: We performed a Bayesian network meta-analysis combining direct and indirect evidence from randomized controlled trials (RCTs) examining efficacy and safety of adalimumab biosimilars versus adalimumab in patients with active RA despite MTX therapy. RESULTS: Overall, 8 RCTs involving 3577 patients, including 8 biologic types, met the inclusion criteria. MSB11022 is listed at the top left of the diagonal of the league table, as it was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the American College of Rheumatology 20 (ACR20) response rate; FKB327 is listed at the bottom right of the diagonal of the league table, as it was associated with the least favorable results. Based on SUCRA, MSB11022 presented the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.623), followed by PF-06410293, CinnoRA, BI 695501, ABP 50, Exemptia, SB5, adalimumab, and FKB327 (SUCRA = 0.390); no difference was observed in ACR20 response rates between biosimilars and adalimumab. Although statistically non-significant, differences in safety ranking were observed for serious adverse events (SAEs) among the interventions, with MSB11022 presenting the highest probability of being safe (SUCRA = 0.865) and Exemptia the lowest (SUCRA = 0.300). CONCLUSION: No significant difference was detected between adalimumab biosimilars and the originator in terms of ACR20 response rates and SAEs in the studied patients.
33998910 Exploring the role of polyphenols in rheumatoid arthritis. 2021 May 17 Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disorder which is mainly characterized by inflammation in joints, bone erosions and cartilaginous destruction that leads to joint dysfunction, deformation, and/or permanent functional impairment. The prevalence of RA is increasing, incurring a considerable burden on healthcare systems globally. The exact etiology of RA is unknown, with various pathways implicated in its pathophysiology. Non-steroidal anti-inflammatory drugs (NSAIDs) including celecoxib, diclofenac and ibuprofen, disease-modifying anti-rheumatic drugs (DMARD) including azathioprine, methotrexate and cyclosporine, biological agents including anakinra, infliximab, and rituximab and immunosuppressants are used for symptomatic relief in patients with RA, but these medications have severe adverse effects such as gastric ulcers, hypertension, hepatotoxicity and renal abnormalities which restrict their use in the treatment of RA; new RA treatments with minimal side-effects are urgently required. There is accumulating evidence that dietary polyphenols may show therapeutic efficacy in RA through their antioxidant, anti-inflammatory, apoptotic, and immunosuppressant activities and modulation of the tumor necrosis factor-α (TNF-α), interleukin (IL)-6, mitogen-activated protein kinase (MAPK), IL-1β, c-Jun N-terminal kinase (JNK), and nuclear factor κ light-chain-enhancer of activated B cell (NF-κB) pathways. While resveratrol, genistein, carnosol, epigallocatechin gallate, curcumin, kaempferol, and hydroxytyrosol have also been studied for the treatment of RA, the majority of data are derived from animal models. Here, we review the various pathways involved in the development of RA and the preclinical and clinical data supporting polyphenols as potential therapeutic agents in RA patients. Our review highlights that high-quality clinical studies are required to decisively establish the anti-rheumatic efficacy of polyphenolic compounds.
34538944 Safety and efficacy of tocilizumab for rheumatoid arthritis: a systematic review and meta- 2021 The present systematic review and meta-analysis was conducted to assess the effect of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA). We systematically searched all potential articles in the main databases, including PubMed, Scopus, EMBASE, Web of Sciences (ISI), and Cochrane Center. The search was subsequently updated in December 2020. The initial review and extraction of information were performed independently by two authors to collect the first author and publication year; sample size; mean age of the intervention and control groups; the dose of TCZ, and the follow-up duration. Outcomes of interest include the ACR20, ACR50, ACR70, total complication rate, and the occurrence of remission. Any disagreements between the reviewers were resolved by discussion and re-check of the article and consultation with a third reviewer. After reviewing and culling, 15 clinical trials comparing the clinical efficacy of TCZ and its comparators in the treatment of patients with RA entered the qualitative and quantitative synthesis. Tocilizumab 8 mg was statistically better than 4 mg or placebo for ACR responses. Significant clinical adverse events in patients with RA treated with TCZ, such as abnormal liver function tests (LFTs) and infections, were more frequent than in comparator groups. This systematic review and meta-analysis suggest that the combination therapy of TCZ with other drugs such as methotrexate and disease-modifying antirheumatic drugs has been studied for various clinical effects concerning safety and clinically significant adverse events. Although the data are promising, long-term performance and safety data need to be fully identified, as well as the risks and benefits of TCZ, especially appropriate timing, dosage, and regimen.
34869276 A Three-Dimensional Co-Culture Model for Rheumatoid Arthritis Pannus Tissue. 2021 Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.
34955646 iTRAQ and PRM-Based Proteomic Analysis Provides New Insights into Mechanisms of Response t 2021 BACKGROUND: Approximately 30% of patients with rheumatoid arthritis (RA) respond poorly to combination therapy of multiple drugs. The molecular mechanisms of different responses to methotrexate + leflunomide + infliximab therapy in patients with RA were explored in this study. METHODS: Infliximab was administered to patients with RA whose disease activity score was higher than 5.1 after 1 month of combination therapy with methotrexate and leflunomide. After 14 weeks of undergoing triple therapy, patients with RA were classified as responders and non-responders. Protein profiles at baseline and 14th week were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and proteins with significant differences ≥1.2 folds change or ≤0.8 folds change were defined as differentially expressed proteins (DEPs). Overlapping DEPs between responders and non-responders were confirmed by parallel reaction monitoring (PRM). Bioinformatic analyses were performed for DEPs. RESULTS: The results revealed 5 non-responders (NRs) and 15 responders (Rs). iTRAQ analysis indicated 13 overlapping DEPs and included 6 opposite change DEPs such as testicular tissue protein Li 70, cofilin 1, fibrinogen beta chain, galectin-10, serotransferrin (TF) and albumin. The difference in serotransferrin between responders and non-responders confirmed by PRM was significant. Verification by PRM indicated that TF was elevated in the Rs group and was reduced in the NRs group. Bioinformatic analysis indicated that serotransferrin was involved in the hypoxia-inducible factor-1 pathway and ferroptosis. CONCLUSION: Serotransferrin-related molecular mechanism may be a new direction to study refractory RA.
33627579 [Spontaneous intracranial hypotension complicated by atlantoaxial subluxation: a case repo 2021 Mar 25 A 54-year-old woman presented at the hospital with headache and posterior neck pain, which worsened when standing or in the sitting position and improved when in the supine position. A diagnosis of rheumatoid arthritis was made at the age ofin 33 years, and the patient has been taking methotrexate and methylprednisolone. Cervical MRI and magnetic resonance myelography showed the appearance of CSF leakage, resulting in a diagnosis of spontaneous intracranial hypotension. A diagnosis of atlantoaxial subluxation was also made based on the abnormal anterior position of the atlas (C1) in the cervical X-ray image. The CSF leakage corresponded with the atlantoaxial subluxation region, which indicated that spontaneous intracranial hypotension was caused by the compression of the dura mater. These symptoms were improved following treatment with the intravenous drip of the extracellular fluids, and she was discharged from the hospital on day 25. The disruption of the dura matter induced by atlantoaxial subluxation is a rare complication but is worth considering when determining the etiology of spontaneous intracranial hypotension.
33410952 Left ventricular myocardial strain assessed by cardiac magnetic resonance feature tracking 2021 Jan 7 PURPOSE: The aim of the study was to assess a relationship between the occurrence of rheumatoid arthritis (RA) and its selected clinical parameters, and left ventricular myocardial strain. MATERIAL AND METHODS: Fifty-six subjects were qualified for the study: 30 RA patients and 26 subjects without rheumatoid diseases. The study design included taking medical history, assessment of the disease activity using selected scales of activity, collecting samples of venous blood to assess selected laboratory parameters and the assessment of cardiac magnetic resonance (CMR). Using the feature tracking method, the following parameters of the left ventricular myocardial strain were assessed: longitudinal strain (LS), radial strain (RS) and circumferential strain (CS). RESULTS: Regarding global values, peak LS and peak CS were statistically significantly lower in RA patients than in the control group. In the whole study group, the factors independently related to low global LS peaks were as follows: occurrence of RA, occurrence of arterial hypertension, increased activity of antibodies against cyclic citrullinated peptide and increased concentration of neutrophil gelatinase-associated lipocalin. The occurrence of RA, occurrence of diabetes, tobacco smoking, higher activity of antibodies against cyclic citrullinated peptide and current use of methotrexate are the risk factors for low peak of global CS. The current use of steroids constitutes a protecting factor against low global CS peaks. CONCLUSION: In subjects with no clinically manifested cardiac damage, RA is associated with a deteriorated left ventricular systolic function assessed by left ventricular myocardial strain measured by CMR feature tracking.
34430606 Cost-effectiveness of Anbainuo plus methotrexate compared to conventional disease-modifyin 2021 Jul BACKGROUND: This study aimed to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) vs. conventional disease-modifying antirheumatic drugs (cDMARDs) in Chinese rheumatoid arthritis (RA) patients. METHODS: A total of 90 RA patients who underwent ABN + MTX [assigned as ABN + MTX group (n=47)] or cDMARDs [assigned as control group (n=43)] treatment were analyzed. Disease activity was assessed at baseline (M0), 3(rd) month (M3), 6(th) month (M6), and 12(th) month (M12) after treatment. Drug, other medical, indirect, and total costs were calculated. Then, pharmacoeconomic analyses were performed with the threshold of cost-effectiveness set as 3 times of the mean gross domestic product (GDP) per capita in China during the study period. RESULTS: Treatment response rate was similar between the 2 groups, while disease remission and low disease activity (LDA) rates were increased in the ABN + MTX group compared to control group. Drug cost, other medical costs, and total cost were higher in the ABN + MTX group than control group, while indirect cost was similar between the 2 groups. Meanwhile, the quality-adjusted life-years (QALY) in ABN + MTX group and control group were 0.72 and 0.48 years, respectively. The incremental cost-effectiveness ratios (ICER) of ABN + MTX group compared to control group among the entire participant cohort, moderate-disease-activity participants, and severe-disease-activity participants were ¥135,486.7, ¥146,450.4, and ¥124,987.2/QALY, respectively, which were all below the cost-effectiveness threshold. Further sensitivity analyses revealed that the cost-effectiveness of ABN + MTX vs. cDMARDs was relatively robust, while among all the indexes, ABN price and Health Assessment Questionnaire Disability Index (HAQ-DI) score change for the ABN + MTX group affected ICER most. CONCLUSIONS: Treatment with ABN + MTX offers acceptable cost-effectiveness compared to cDMARDs treatment in Chinese RA patients.
33841689 Effect of combined application of iguratimod in the treatment of active rheumatoid arthrit 2021 OBJECTIVE: This study was designed to analyse the effect of combined application of iguratimod with methotrexate in the treatment of active rheumatoid arthritis (RA). METHODS: A total of 115 patients with active RA admitted to our hospital were enrolled and divided into group A (n=58) and group B (n=57) according to the method of random number table. Patients in group B were treated with methotrexate alone, while patients in group A were treated with methotrexate combined with iguratimod. The curative efficacy was compared between the two groups. RESULTS: At 6 months after treatment, the levels of CTX-1 and RANKL in group A were higher than those in group B, and the levels of OPG, IL-17 and TGF-α in group A were lower than those in group B (P<0.05). The level of Th17 cells in group A was higher than that in group B, and the level of Treg cells in group A was lower than that in group B at 6 months after treatment (P<0.05). Tender joints count, swollen joints count and DAS28 score in group A were less than those in group B at 6 months after treatment (P<0.05). The duration of morning stiffness of the joints and the score of joint pain degree in group A were less than those in group B at 1, 2, 3, 4, 5, and 6 months after treatment (P<0.05). CONCLUSION: The combined application of methotrexate and iguratimod in the treatment of active RA can effectively improve bone metabolism, regulate the levels of Th17 and Treg cells, play a prominent role in anti-inflammatory effect, and relieve symptoms, and thus achieve a more satisfactory curative effect.
34178513 Pancytopenia Resulting From Low-Dose Methotrexate Use: A Diagnostic Challenge. 2021 May 23 Rheumatoid arthritis (RA) is a common autoimmune disease primarily affecting small joints which leads to crippling erosion of the articular cartilage and bone. It is associated with complications related to both its disease course and treatment. Methotrexate (MTX) is a folate antagonist responsible for modulating cell-specific signaling pathways and inhibiting the proinflammatory properties of major cell lineages involved in the pathogenesis of RA. It is considered to be the first-line agent in RA because of its disease-modifying ability and safety profile at low doses. This case report discusses how a middle-aged female presented with severe bone marrow suppression secondary to MTX toxicity, an unusual presentation at the usual low-dose regimen. Her presentation overlapped with several other conditions, especially with Felty's syndrome, a rare complication of RA, characterized by the triad of splenomegaly, neutropenia, and RA. Other differentials included hemophagocytic lymphohistiocytosis, hematologic neoplasms, drug reaction, and infection. Therefore, it was essential to exclude all possible differentials before initiating therapy. We found the corrected reticulocyte count coupled with a good response to leucovorin to be an effective way to differentiate MTX-induced pancytopenia from other possible hematologic diagnoses without the use of a bone marrow biopsy. Additionally, our case incidentally demonstrated a potential interaction between piperacillin/tazobactam and MTX.
34765383 Evaluating the Use of Hydroxychloroquine in Treating Patients With Rheumatoid Arthritis. 2021 Nov Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases present today. Although treatment options may differ among clinicians, a commonly prescribed treatment is hydroxychloroquine (HCQ), alone or in combination with other medications. HCQ has been studied for its immunomodulatory effects as well as its role in treating adverse conditions associated with RA. This systematic review examined the use of HCQ therapy in RA patients. A systematic search for relevant literature through PubMed, National Institute of Informatics, Japan (CiNii), and Science Direct databases were carried out in August 2021. Literature directly related to HCQ therapy for RA patients, RA-associated chronic kidney disease, and cardiovascular disease (including lipid profile) was considered relevant. HCQ associated retinopathic adverse effects were also selected for this review. Thirty-eight articles were found to be relevant, passed quality assessment, and were included in this review. Nine articles discussed HCQ therapy in comparison with other therapies (mainly methotrexate and sulfasalazine), but were contradictory in their outcomes, as were the seven papers that reviewed kidney function in RA patients with and without HCQ. Five articles credited better cardiovascular outcomes to RA patients taking HCQ. Sixteen articles studied the relationship between HCQ and retinal toxicity, providing insights into the risks associated with HCQ therapy. HCQ therapy was found not only to be beneficial in slowing the disease progression in RA patients but enhanced the effects of methotrexate in treating RA as well. Data strongly associates HCQ therapy with the mitigation of RA-related cardiovascular and kidney conditions. However, if HCQ is prescribed, it is imperative to be aware of the possible (although rare) retinopathic adverse effects associated with this therapy.
34290965 A double-blind placebo-controlled randomized trial of oral saffron in the treatment of rhe 2021 Jul OBJECTIVE: Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This is a double-blind, placebo-controlled, randomized clinical trial (RCT) performed on 55 newly- diagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups. Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90(th) day of the study. RESULTS: There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. CONCLUSION: In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy.
33910632 Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients w 2021 Apr 28 BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk. OBJECTIVE: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone. METHODS: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method. RESULTS: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found. CONCLUSION: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.
34135672 Relationship between different anti-rheumatic drug therapies and complementary and alterna 2021 May OBJECTIVES: The use of complementary and alternative medicine (CAM) by patients with rheumatoid arthritis (RA) is highly prevalent. The relationship of these remedies with disease therapy are not fully studied. We aimed to explore the relationship between different anti-rheumatic drug therapy and CAM use in RA patients. METHODS: The study used an interview-based cross-sectional survey in two major referral centres in Riyadh, Saudi Arabia. Patients were adults with confirmed RA that attended rheumatology clinics. Information on the utilization of CAM, RA duration, drug therapy, and laboratory parameters were obtained. Descriptive statistics as well as adjusted odds ratio using bivariate logistic regression were used to explore the different factors related to CAM use, including drug therapy. RESULTS: A total of 438 adult patients with RA were included. The mean (±SD) age of the patients was 49 (±15.0) years. The majority were women 393 (89.7%). Two hundred and ninety-two patients (66.7%) had used CAM. The CAM users who had a longer disease duration (AOR 1.041 [95% CI: 1.011, 1.073]; p = 0.008) were more likely to be female (AOR 2.068 [95% CI: 1.098, 3.896]; p = 0.024), and use methotrexate (AOR 1.918 [95% CI: 1.249, 2.946]; p = 0.003) as opposed to celecoxib (AOR 0.509 [95% CI: 0.307, 0.844]; p = 0.009) and biologic monotherapy (AOR 0.443 [95% CI: 0.224, 0.876]; p = 0.019). Other factors related to CAM were meloxicam use (AOR 2.342 [95% CI: 1.341, 4.089]; p = 0.003) and traditional therapy (AOR 2.989 [95% CI: 1.647, 5.425]; p = 0.000). The remaining factors were not significant. CONCLUSION: CAM use is prevalent in patients with RA. Understanding patients and disease related factors associated with higher use of CAM is warranted to improve RA management and provide more rational use of these remedies.
34878205 The development and validation of a Patient-Perceived Methotrexate Intolerance Scale for u 2021 Dec 8 INTRODUCTION/OBJECTIVE: To develop a scale to measure methotrexate intolerance for use in adult rheumatoid arthritis (RA) patients and to describe its psychometric properties. METHODS: A three-phase study was conducted. During Phase 1, we conducted individual interviews with RA patients (n = 14) to inform our item development process. During Phase 2, we asked for RA patients' (n = 10) feedback on item readability, clarity and the scale's ability to measure methotrexate intolerance. During Phase 3, we had patients with RA (n = 204) complete the scale to develop a final version and to describe the scale's internal validity (Cronbach's alpha), test-retest reliability (intra-class correlation coefficients), construct validity and discriminant validity and the ability of the scale to discriminate between past and present methotrexate users. RESULTS: The newly developed, weighted scale (Patient-Perceived Methotrexate Intolerance Scale [PPMIS]) includes four subscales: Methotrexate Benefits, Methotrexate Risks-Side Effect Considerations, RA Risks and Methotrexate Risks-Willingness to Take Methotrexate Despite Risks. Cronbach's alpha ranged from 0.79 to 0.94. Test-retest reliability at 2 weeks was 0.73-0.88. Construct validity was supported with significant logical relationships between subscale scores and the existing methotrexate intolerance scale and past/present methotrexate use. The PPMIS was able to correctly classify RA patients as a past versus present methotrexate user 77% of the time. At the cut point of 3.29, the sensitivity of the PPMIS is 74% and specificity is 72% to correctly classify patients into past/present methotrexate use. CONCLUSION: This is the first known scale with favourable measurement properties to evaluate methotrexate intolerance using a patient-centred perspective.
34041071 Evaluation of prescription practices in rheumatoid arthritis at the rheumatology clinic in 2021 Feb OBJECTIVE: This study was aimed to analyze the prescription pattern of disease modifying anti-rheumatic drug (DMARD) therapy in patients with rheumatoid arthritis (RA) in a tertiary care teaching hospital in Uttarakhand, India. METHODOLOGY: This cross-sectional study was conducted in 150 RA patients who were given DMARD therapy. Patient's demographic details, drugs prescribed with their dosage and administration routes and the usage of complementary and alternative medicine (CAM) therapy were recorded to study the prescription pattern. RESULTS: Overall, 4 DMARDs were prescribed in all the studied patients: Methotrexate (n = 150), hydroxychloroquine (n = 35), leflunomide (n = 5), and adalimumab (n = 1). Single DMARD therapy with methotrexate was prescribed to 110 (73.3%) followed by double therapy with methotrexate + hydroxychloroquine in 35 (23.3%), triple therapy (methotrexate + hydroxychloroquine + leflunomide) in 4 (2.7%) and triple therapy with biological DMARD (methotrexate + hydroxychloroquine + leflunomide + adalimumab) in 1 (0.7%) patient. Adjuvant therapy drugs included: Prednisolone (n = 150), folic acid (n = 150), naproxen (n = 150), calcium (n = 150), vitamin D (n = 150) and indomethacin (n = 40). Of the total, 61.4% patients also took complimentary alternative medicine (CAM) therapy. CONCLUSION: Our study concludes that the most commonly prescribed DMARDs in our setting, to patients of RA, in descending order of frequency were methotrexate, followed by hydroxychloroquine, leflunomide and lastly adalimumab. A total of five adjuvant medications were commonly prescribed to all patients. There was a high prevalence of self-medicated CAM therapy in the majority of these patients.
34659493 The role of upadacitinib in the treatment of moderate-to-severe active rheumatoid arthriti 2021 Despite recent promising developments in the treatment of rheumatoid arthritis (RA), a substantial proportion of patients still cannot achieve the treatment targets: low disease activity and remission. Janus kinase (JAK) inhibitors have the potential to fill this important gap with their high efficiency, rapid onset of action, and acceptable safety profile. The fact that the previously approved two JAK inhibitors, tofacitinib and baricitinib, inhibit more than one JAK molecule raised the question whether a safer profile can be possible by inhibiting fewer JAK molecules. Upadacitinib, a JAK 1 selective molecule developed in this context has been evaluated in the SELECT phase-III study program and demonstrated a high and rapid efficacy in monotherapy as well as in combination with csDMARDs both in csDMARD-naive RA patients and in patients refractory to csDMARD and bDMARD treatments. Upadacitinib 15 mg once daily displayed a similar safety profile except for increased creatine phosphokinase (CPK) levels and herpes zoster (HZ) risk compared to its active comparators methotrexate (MTX) and adalimumab. Most of the CPK elevations were asymptomatic, and most of the HZ cases were not serious. Along with the randomized-controlled studies and meta-analysis results, upadacitinib 15 mg once daily has a favorable efficacy/safety profile. Long-term extensions of current studies and real-world data will be important to fully appreciate its potential in the treatment of RA.
33796022 Research Progress of Therapeutic Enzymes and Their Derivatives: Based on Herbal Medicinal 2021 Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.