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ID PMID Title PublicationDate abstract
31586982 [Rheumatoid arthritis in elderly people]. 2019 Rheumatoid arthritis (RA) is a chronic, systemic connective tissue disease, characterized by progressive, destructive polyarthritis with internal organs involvement due to active, systemic inflammation. The onset of disease occurs usually in 4th or 5th decade of life. Since the general population is ageing, beginning of RA in older age is more and more common. The term elderly onset of rheumatoid arthritis (EORA) describes the disease with onset at age over 60. Several observational studies indicated, that proportion of women and men is comparable in EORA. Clinical course of the disease is characterized by sudden onset with general constitutional symptoms, high disease activity and inflammatory parameters. Involvement of large joints is more common, specially shoulder joints. Antibodies typical for RA (rheumatoid factor, anti-citrullinated peptide) are usually negative. More advanced destructive changes of joints and functional impairment are also characteristic for EORA patients in comparison with younger onset of RA (YORA). In clinical practice the use of methotrexate and biological drugs is less common, and glucocorticosteroids more common in EORA. Due to high RA activity, patients with EORA should be treated in the same way as YORA, with careful monitoring due to higher risk of adverse events associated with treatment.
31648623 Methotrexate pharmacogenetics in the treatment of rheumatoid arthritis. 2019 Nov For many decades, methotrexate (MXT) has remained the drug of choice in the treatment of rheumatoid arthritis (RA). Unfortunately, a considerable number of patients do not achieve an appropriate therapeutic response. Pharmacogenetics studies do not give usable results regarding differences in MTX response among RA patients. The mechanism of MTX action in RA is not completely understood. We present and discuss data regarding the molecular basis of folate and adenosine pathways, the most obvious MTX targets, to explain possible causes of therapy failure. The molecular basis of the disease could also have an impact on therapy outcomes and in this review we explore this. Finally, we make a short review of available pharmacogenetics study results.
30955397 Comparison of Janus kinase inhibitors in the treatment of rheumatoid arthritis: a systemic 2019 Jun Several Janus kinase (JAK) inhibitors, oral targeted disease-modifying drugs, will be approved for the treatment of rheumatoid arthritis (RA) and other diseases. This review compares and contrasts the efficacy of JAK inhibitors (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib and decernotinib) in RA including: early RA methotrexate-naive patients, post methotrexate failure and post biologics. Trials in monotherapy, combination with disease modifying drugs such as methotrexate, and comparing with adalimumab in biologic-naive patients were studied. The efficacy is superior to methotrexate in naive patients and equal or superior to adalimumab depending on the drug and dose. There is a class effect of adverse events. Serious infections occur at a rate similar to other advanced therapies in RA, although more reactivation of herpes zoster occurs.
31049664 [Comorbidities-Their role in the treat to target concept for rheumatoid arthritis]. 2019 Jun Treat to target (T2T) strategies and comorbidities are closely related. Strong evidence exists for reducing the risk and extent of comorbidities, such as cardiovascular (CV) diseases, depression and infections by implementing T2T concepts and inducing good disease control of rheumatoid arthritis (RA) in this way. On the other hand existing comorbidities may hinder implementation of T2T concepts by aggravating RA or influencing rheumatologists to overcautiously use DMARD treatment. Among a long list of potentially relevant comorbidities with RA, in this review two particularly relevant accompanying diseases with respect to T2T, CV diseases and infections, are selected for discussion in detail. The CV comorbidities are the main cause of death for RA patients and are triggered by RA-associated inflammatory mechanisms. Their negative influence on implementation of T2T strategies can be stopped or at least reduced by optimal control of RA activity with the help of selecting drugs with cardioprotective properties (such as biologicals, methotrexate and hydroxychloroquine) as well as assessing and treating traditional CV risk factors. Infections are among most important adverse events of DMARD treatment and can disturb the optimal use of these drugs and so hinder the success of the T2T strategy. Optimal infection prophylaxis and identification of high risk patients are particularly important and minimization of glucocorticoid use is critical to reduce the risk of infections. In summary, comorbidities are important potential risk factors for the success of T2T strategies.
31866617 Immune response in LPD during methotrexate administration (MTX-LPD) in rheumatoid arthriti 2019 Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Although the risk of LPD development increases by RA inflammation itself, observation of spontaneous regression of LPD after MTX discontinuation lead to the theory of lymphomagenic role of MTX. In this review, we focused on the several immune response involved in LPD that developed under MTX administration in RA patients.
30983549 Association between ABCB1 C3435T polymorphism and methotrexate treatment outcomes in rheum 2019 Apr Aim: This study was conducted to investigate the relationship between ABCB1 gene C3435T polymorphism and methotrexate treatment outcomes in rheumatoid arthritis patients. Methods: Seven electronic databases (PubMed, EMBASE, Web of Science, Cochrane, OVID, Chinese biomedical literature [CBM], China National Knowledge Infrastructure [CNKI] and Wanfang databases) were searched to select eligible publications until 18 July 2018. The references of relevant articles were also manually searched. The quality evaluation of the included studies was carried out according to the guidelines of the Newcastle-Ottawa Scale. Data were analyzed with Review Manager 5.3 and Stata 13.0 software. In total, 12 articles involving 2014 patients were included. Conclusion: Our results demonstrated that the ABCB1 gene C3435T polymorphism might be a reliable predictor of response to methotrexate in rheumatoid arthritis patients. However, well-designed, multicenter and large-scale prospective studies are required to further confirm the validity of our results.
31611592 Folyl polyglutamate synthethase (FPGS) gene polymorphisms may influence methotrexate adver 2020 Apr The aim of the study was to look for the association of FPGS 2752 G > A (rs1544105), FPGS 1994 A > G (rs10106), and GGH 452 C > T (rs 11545078), GGH -401C > T (rs 3758149) gene polymorphisms with methotrexate (MTX) treatment response and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). Further the influence of these gene polymorphisms on MTX polyglutamate levels was analyzed. A total of 330 patients with RA were investigated. FPGS gene polymorphisms were analyzed by TaqMan 5'nuclease assay and GGH gene polymorphisms were analyzed by PCR-RFLP. Methotrexate polyglutamates (nmol/L of packed erythrocytes) were measured by liquid chromatography mass spectrometry (LCMS/MS) method. We found that the heterozygous genotype of FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15-3.35)] and FPGS rs10106 AG genotype [p = 0.01, OR 2.11, 95% CI (1.20-3.71)] were associated with MTX adverse events. FPGS rs1544105 and GGH -401C > T SNPs influenced the polyglutamate levels. None of the investigated SNPs seems to be associated with MTX treatment outcome.
31413870 Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: review of ra 2019 Treatment of rheumatoid arthritis (RA) has improved substantially during the last decades, mainly due to the development and introduction in everyday practice of new, highly efficacious, disease-modifying antirheumatic drugs (DMARDs), more optimal usage of them, earlier diagnosis and tighter control of disease activity targeting at remission. Methotrexate is still today the anchor drug and the first-line treatment after diagnosis. However, numerous studies comparing methotrexate and biologic DMARDs, as well as new targeted synthetic DMARDs, both in early as in more established disease, have shown consistently better efficacy of the latter compared with methotrexate, with methotrexate yielding remission to maximum half of patients. This could suggest a new paradigm shift with earlier start of a biologic or a targeted synthetic DMARD, with the possibility of subsequent discontinuation in case of achievement of stable remission. Several strategy trials, however, have shown that there might be a clinical and structural benefit of initial, aggressive therapy, possibly even associated with higher chance of remaining in remission, after cessation of the biologic DMARD and continuing with methotrexate alone, but they have failed to show a clear advantage of such an aggressive treatment strategy. This might become a valuable option for the future treatment algorithm of RA, especially for a subgroup of patients with RA, but further confirmation from future research is needed. The crucial role of glucocorticoid use as part of the combination strategy should be acknowledged, and strategy trials should include this combination as an active comparator.
31350580 Reverse shoulder arthroplasty for rheumatoid arthritis since the introduction of disease-m 2019 Nov PURPOSE: Rheumatoid arthritis has been associated with poor clinical outcomes in hemiarthroplasty and unconstrained total shoulder arthroplasty. The reverse shoulder arthroplasty can be utilized to address the shortcomings of hemiarthroplasty and unconstrained total shoulder arthroplasty in the inflammatory arthritis patient population. The objective of the present study was to retrospectively review clinical and radiographic outcomes of patients who underwent reverse shoulder arthroplasty for rheumatoid arthritis and other inflammatory arthropathies and provide a comprehensive analysis to identify factors that may alter patient outcomes. METHODS: We identified 91 primary reverse shoulder arthroplasties performed between 2006 and 2013 in patients with inflammatory arthritis. Seventy-five had at least two years of follow up with an average follow-up of 4.0 years. The average age at the time of surgery was 70 years old. Peri-operative use of steroids, biologics, and methotrexate were reviewed. Outcomes evaluated included revision and reoperation rates, complications, American Shoulder and Elbow Surgeons (ASES) scores, simple shoulder test (SST) scores, component loosening, and scapular notching. RESULTS: The two and five year implant revision-free survival was 99%. The two and five year re-operation-free survival was 97%. Eighteen (24%) glenoid components required augmentation with corticocancellous autograft from the humeral head. There were two cases of glenoid loosening with gross changes in position. Patients experienced significant pain relief with a 92% satisfaction rate. Shoulder elevation and external rotation improved from 65 and 21 degrees pre-operatively to 138 and 45 degrees post-operatively, respectively (p < .01). Average ASES and SST scores were 72 and 7.0, respectively. The use of prednisone, DMARDs, or biologic medications had no significant impact on outcomes.
31444259 DPP-4 inhibitor (sitagliptin)-induced seronegative rheumatoid arthritis. 2019 Aug 22 Sitagliptin is a dipeptidyl peptidase-4 inhibitor commonly used in the treatment of type 2 diabetes mellitus for glycaemic control. Concerns have arisen regarding adverse events caused by this drug, particularly concerning arthralgias. Here, we report on a 56-year-old man being treated with sitagliptin who developed inflammatory arthritis after taking the drug for 6 months. The patient presented with pain, swelling and erythema in multiple joints and was eventually diagnosed with seronegative rheumatoid arthritis (RA) under the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria. His symptoms continued for several months after stopping sitagliptin and eventually went into remission after a tapered course of steroids, hydroxychloroquine and methotrexate. Furthermore, the patient is HLA-DRB3 positive, a genetic marker that is still being investigated for its role in the pathogenesis of RA and that may have been a predisposing factor in the development of this patient's inflammatory arthropathy.
30955063 Leveraging Google Trends to investigate the global public interest in rheumatoid arthritis 2019 Aug This study aims to investigate the global public interest in rheumatoid arthritis by evaluating search term popularity changes of the disease over a decade. Google Trends was applied to retrieve search popularity scores for the term 'rheumatoid arthritis' between January 2004 and December 2017, utilizing the category of "health". Overall, relative searches volume for rheumatoid arthritis steadily decreased from January 2004 to December 2010, and then slowly rose from January 2011 to December 2017. There were significant seasonal variations in relative searches volume for the term 'rheumatoid arthritis' (Amplitude = 3.11; Phase: Month = 4.3; Low point: Month = 10.3; p < 0.025). Relative searches volume peaked in April and reached the lowest level in October. The top 11 rising topics were scleroderma, Anna Marchesini, C-reaction protein, osteoarthritis, arthritis, joint pain, autoimmune disease, rheumatoid factor, rheumatology, methotrexate, and systemic lupus erythematosus, ranking from high to low by relative growth of topic regarding rheumatoid arthritis. In conclusion, the evidence from Google Trends analysis demonstrates a significant seasonal variation in rheumatoid arthritis, with a peak in April. In addition, the top rising search queries are beneficial for physicians to search the Internet themselves for websites that provide high-quality information to recommend to their patients.
30890833 Epidemiology of rheumatoid arthritis, clinical aspects and socio-economic determinants in 2019 Mar OBJECTIVE: The study aimed to evaluate literature on rheumatoid arthritis disease in Pakistani patients, to have an understanding about its epidemiology, clinical aspects and socio-economic determinants. METHODS: The review study was conducted from December 2017, to May 2018. An online search was conducted in international and local health databases using appropriate search keywords as well as scanning reference lists of related articles. Literature published after year 2000 that reported epidemiological, demographic, clinical and socioeconomic data of Pakistani rheumatoid arthritis patients was included. Meta-analysis was performed where possible. This systematic review was registered on the international prospective register of systematic reviews PROSPERO (CRD42018090582). RESULTS: Of the 334 research articles found, 29 (8.7%) were selected. Patients were mostly females, but no study explored impact of disease on household and family role functioning of rheumatoid arthritis-affected women in Pakistan. Most patients were uneducated (55%) and unemployed; had low disease knowledge (N = 149, 74.5%) and poor adherence to disease-modifying anti-rheumatic drugs (N = 23, 23%). Point prevalence of rheumatoid arthritis reported from Karachi was high at 26.9%. Moderate disease activity, i.e., 4.5}0.7 and mild functional disability (N = 66, 51.6%) were seen in RA patients. Almost half (N = 799, 46.9%) had comorbidities. Almost a fifth proportion of RA patients had dyslipidaemia as a comorbidity (N = 134, 16.77%) and higher cardiovascular risk score as modifiable risk factor. Undiagnosed depression (N = 134, 58.3%) and low bone mineral density (N = 93, 40.6%) were reported in RA patients. Direct monthly treatment cost of disease was significantly high considering patients' socio-economic status, i.e., USD 16.47 - 100.68. Most commonly used drug was methotrexate. CONCLUSIONS: There is a paucity of data on Pakistani rheumatoid arthritis patients' demographic and socio-economic parameters, especially the gender element.
31295614 Intracranial Methotrexate-Associated Lymphoproliferative Disorder in Rheumatoid Arthritis. 2019 Oct BACKGROUND: Methotrexate (MTX) is widely used as an anchor drug for the treatment of rheumatoid arthritis (RA) because of its ability to control pain and inflammation. However, few studies have shown that long-term MTX use can lead to lymphoproliferative disorders (LPDs) in these patients. Here we describe a rare case of intracranial MTX-associated LPD in a patient with RA. CASE DESCRIPTION: A 68-year-old woman was admitted to our hospital because of progressive right limb palsy. She was diagnosed with RA 15 years ago and has been receiving MTX therapy for the past 5 years. Magnetic resonance imaging of the head revealed a ring-enhancing lesion in the left parietal lobe. Open biopsy was performed for making a definite diagnosis and planning treatment. Hematoxylin-eosin stain revealed dense proliferation of atypical lymphocytes in the perivascular lesion. Immunohistochemistry results were positive for CD20; this lesion was observed as a strong nuclear signal on in-situ hybridization for the Epstein-Barr virus-encoded RNA. Finally, the patient was diagnosed with MTX-associated LPD. We discontinued MTX administration and initiated steroid therapy for RA. The intracranial lesion reduced in size, and her symptoms resolved after MTX discontinuation; no recurrence has been observed at 3 years after MTX discontinuation. CONCLUSIONS: Intracranial MTX-associated LPD is extremely rare. Here we describe a particular case and review the literature pertaining to intracranial MTX-associated LPD. More attention should be paid to LPD in a patient receiving immunosuppressive treatment for RA.
31451091 High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Man 2021 Jun BACKGROUND: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. OBJECTIVE: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. METHODS: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. RESULTS: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). CONCLUSION: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.
31692815 VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis. 2019 Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.
31342647 Sarcopenia-associated factors in Japanese patients with rheumatoid arthritis: A cross-sect 2019 Sep AIM: To evaluate the prevalence rate and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis. METHODS: We enrolled 240 consecutive patients with rheumatoid arthritis aged ≥65 years in this study. We examined clinical data: age, sex, body mass index, disease duration, rheumatoid factor positivity, anti-cyclic citrullinated peptide antibody positivity, biological or target synthetic disease-modifying antirheumatic drug use, methotrexate use, glucocorticoid use, C-reactive protein level, disease activity score in 28 joints-erythrocyte sedimentation rate, Health Assessment Questionnaire Disability Index, bone mineral density of the lumbar spine and total hip, grip strength, gait speed, and relative skeletal muscle mass index by bioelectrical impedance analysis. Sarcopenia was defined according to a consensus report by the Asian Working Group for Sarcopenia. RESULTS: The prevalence rate of sarcopenia was found to be 29.6%. Multivariate analysis identified the following factors to be associated with sarcopenia: age (P = 0.008; odds ratio 1.08), body mass index (P < 0.001; odds ratio 0.73), C-reactive protein (P = 0.017; odds ratio 1.76) and hip bone mineral density (P = 0.037; odds ratio 0.61). CONCLUSIONS: The sarcopenia-associated factors were age, body mass index, C-reactive protein and hip bone mineral density in Japanese patients with rheumatoid arthritis. Because the Health Assessment Questionnaire Disability Index, a standard measurement of function, cannot predict sarcopenia, the muscle mass needs to be measured while assessing changes in grip strength, body mass index, C-reactive protein and hip bone mineral density. Geriatr Gerontol Int 2019; 19: 907-912.
29696833 Tofacitinib in Rheumatoid Arthritis: Lack of Early Change in Disease Activity and the Prob 2019 Jan OBJECTIVE: Optimal targeted treatment in rheumatoid arthritis requires early identification of failure to respond. This post hoc analysis explored the relationship between early disease activity changes and the achievement of low disease activity (LDA) and remission targets with tofacitinib. METHODS: Data were from 2 randomized, double-blind, phase III studies. In the ORAL Start trial, methotrexate (MTX)-naive patients received tofacitinib 5 or 10 mg twice daily, or MTX, for 24 months. In the placebo-controlled ORAL Standard trial, MTX inadequate responder patients received tofacitinib 5 or 10 mg twice daily or adalimumab 40 mg every 2 weeks, with MTX, for 12 months. Probabilities of achieving LDA (using a Clinical Disease Activity Index [CDAI] score ≤10 or the 4-component Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] ≤3.2) at months 6 and 12 were calculated, given failure to achieve threshold improvement from baseline (change in CDAI ≥6 or DAS28-ESR ≥1.2) at month 1 or 3. RESULTS: In ORAL Start, 7.2% and 5.4% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to show improvement in the CDAI ≥6 at month 3; of those who failed, 3.8% and 28.6%, respectively, achieved month 6 CDAI-defined LDA. In ORAL Standard, 18.8% and 17.5% of patients receiving tofacitinib 5 and 10 mg twice daily, respectively, failed to improve CDAI ≥6 at month 3; of those who failed, 0% and 2.9%, respectively, achieved month 6 CDAI-defined LDA. Findings were similar when considering improvements at month 1 or DAS28-ESR thresholds. CONCLUSION: In patients with an inadequate response to MTX, lack of response to tofacitinib after 1 or 3 months predicted a low probability of achieving LDA at month 6. Lack of an early response may be considered when deciding whether to continue treatment with tofacitinib.
31133043 Rheumatoid nodules in thyroid gland parenchyma as an expression of rheumatoid arthritis: a 2019 May 28 BACKGROUND: The rheumatoid nodule is the most common extra-articular manifestation of rheumatoid arthritis. When present, it is readily identified in conventional hematoxylin and eosin sections. CASE PRESENTATION: We report a case with several rheumatoid nodules in a thyroid gland of a 33-year-old Greek woman with a 3-year history of rheumatoid arthritis treated with methotrexate, after having total thyroidectomy for hypothyroidism. CONCLUSION: To the best of our knowledge, this is the first time that rheumatoid nodules have been encountered in the thyroid gland.
31813294 Factors associated with disease activity after orthopaedic surgery in patients with rheuma 2020 Nov Objective: This study evaluated the effect of surgical intervention on disease activity and factors associated with postoperative disease activity in patients with rheumatoid arthritis (RA).Methods: One hundred and seventy-five patients with RA who underwent a single orthopaedic surgical procedure with 1 year of follow-up were retrospectively reviewed to assess postoperative changes in disease activity using disease activity score in 28 Joints calculated with C-reactive protein (DAS28-CRP). European League against Rheumatology (EULAR) response criteria were used to assess the response to surgical intervention.Results: Overall disease activity was significantly improved after surgery. Therapeutic regimens including biological/targeted-synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs), methotrexate (MTX), and prednisolone (PSL) were not significantly changed 1 year after surgery. Shorter disease duration, surgery of large joints, higher baseline DAS28-CRP, and no use of b/tsDMARDs affected postoperative improvement of disease activity. Multivariate logistic regression analysis revealed that large joint surgery and no preoperative use of b/tsDMARDs were independent factors leading to good response to EULAR criteria after surgery (OR = 2.70; 95% CI, 1.03-7.06; p < .05, OR = 4.09; 95% CI, 1.50-11.14; p < .01, respectively).Conclusion: Significant improvement of disease activity after surgical intervention may be expected in patients with RA with large joint surgeries or no preoperative use of b/tsDMARDs.
31823141 Effect of short-term methotrexate discontinuation on rheumatoid arthritis disease activity 2020 Feb To investigate the effects of short-term discontinuation of methotrexate (MTX) on disease activity in patients with rheumatoid arthritis (RA) taking a stable dose of MTX. A post-hoc analysis of two randomized controlled trials was used to investigate the effects of temporary MTX discontinuation (for 2 weeks or 4 weeks) on responses to seasonal influenza vaccination. The impact of MTX discontinuation on the RA disease activity score (DAS28) and RA flare rate during discontinuation and after reintroduction was examined. The DAS28 increased during the 4-week MTX discontinuation period, before returning to baseline after reintroduction. The overall flare-free survival period did not differ between the groups (log rank p = 0.142). However, during the 4-week MTX discontinuation period, more patients in the MTX-hold group than in the MTX-continue group experienced a flare (20.5% vs. 7.4%, respectively; p = 0.058). After resumption of MTX, the flare rate did not differ between groups. The flare rates in the MTX-continue group and the 2-week and 4-week MTX-hold groups were 5.8%, 10.8% and 20.5%, respectively (p < 0.01). The change in the DAS28 from baseline did not differ significantly between the MTX-continue and the 2-week MTX-discontinue groups. However, there was a significant difference between the 4-week MTX-hold group and the MTX-continue group (p = 0.005). Short-term discontinuation of MTX for up to 2 weeks is safe, whereas discontinuation for 4 weeks is associated with a transient increase in disease flares and activity in RA patients taking a stable MTX dose.Key Points• Methotrexate discontinuation for 2 weeks is safe.• Methotrexate discontinuation for 4 weeks transiently increases flare risk and disease activity.• Disease flare risk and disease activity return to baseline after restarting methotrexate treatment.