Browse

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

ID PMID Title PublicationDate abstract
34869435 Juvenile Idiopathic Arthritis and COVID-19 Pandemic: Good Compliance With Treatment, Reluc 2021 Objective: The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. After national lockdowns, many patients were also concerned about their safety at school. We evaluated the impact of the pandemic on the optimal continuation of treatment and on the return to school in JIA patients. Methods: JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. The primary outcome was DMARD treatment modification in relation to the context of the pandemic but we also evaluated the pandemic's impact on the schooling. Results: One hundred and seventy three patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases. Two patients were diagnosed positive for SARS-CoV-2 infection. Conclusion: This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic and were rarely affected by symptomatic COVID-19. In contrast, parents' reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.
33856543 Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases. 2021 Jun This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases and identify the risk factors associated with severe COVID-19 pneumonia. This was a retrospective study in a tertiary care center conducted through the period between March 2020 and November 2020 and included all adult patients with rheumatic diseases who tested positive on the COVID-19 polymerase chain reaction (PCR) test. We assessed the patients' demographic data, history of rheumatic disease, COVID-19 symptoms and experimental treatment, if any, their disease course, and outcome. In all, 47 patients were included, and most were females. The commonest rheumatic diseases were rheumatoid arthritis (53.2%), followed by systemic lupus erythematosus (21.3%), and psoriatic arthritis (10.6%). Methotrexate and hydroxychloroquine were the most commonly used disease-modifying anti-rheumatic drugs in 36.1% and 25.5%, respectively. Out of 47 patients, 48.9% required hospitalization with a median hospital stay of 7 days. Severe COVID-19 pneumonia, defined as clinical signs of pneumonia plus one of the following: respiratory rate > 30 bpm, severe respiratory distress, or oxygen saturation < 90% in room air was observed in 19.1% of the patients, and one patient died. We found that elderly patients with a mean age of 65.3 years were more likely to develop severe COVID-19 pneumonia and that was statistically significant. Our study showed that elderly patients with a mean age of 65 years and having rheumatic diseases had an increased risk of hospital admission and development of severe COVID-19 pneumonia.
34843092 Patient-Reported Nausea and Fatigue Related to Methotrexate: A Prospective, Self-Controlle 2022 Feb INTRODUCTION: The magnitude and frequency of temporally related methotrexate (MTX)-associated side effects in rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients are difficult to quantify using traditional research methods. As proof of concept designed in part to implement digital data collection for remote patient monitoring, we conducted a study implementing self-controlled case series analytic methods to understand MTX-related symptoms in RA or PsA. METHODS: In study phase 1, adults with RA or PsA from the ArthritisPower(®) Registry (past or current oral MTX users) participated in a cross-sectional survey. In phase 2, current MTX users participated in a longitudinal study and completed the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) 1-day nausea/vomiting and fatigue measure. Within-person change in PROMIS scores between risk (6-36 h post-dose) and control (96-144 h post-dose) windows were compared using mixed models. RESULTS: The baseline survey was completed by 671 participants (mean age: 54 years, 88% female, 92% white, 79% with RA). Among current MTX users (353/671 [53%]), most reported MTX-associated side effects (216/353 [61%]), most frequently fatigue (161/353 [46%]). Among phase 2 participants with (n = 39) and without (n = 84) baseline nausea, mean increase in PROMIS nausea was 5.1 units (P < 0.0001) and 0.7 units (P = 0.135), respectively; among those with (n = 51) and without (n = 72) baseline fatigue, mean increase in PROMIS fatigue was 3.9 units (P = 0.0003) and 0.4 units (P = 0.554), respectively. CONCLUSIONS: Digital remote patient monitoring presents an opportunity to detect and address medication tolerability in real time. Using a novel study design to control for between-person confounding, the magnitude of nausea and fatigue experienced by participants with RA and PsA temporally related to weekly MTX use was substantial.
34042308 Reply. 2021 Sep We appreciate the letter by Mortezavi et. al. describing vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID Vaccine Guidance Task Force was aware of the two studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et. al., patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo‐treated patients (68.4%), a difference of 23.3%, 95% CI −36.6 to −9.6%. The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2%, 95% CI −47.3 to −11.4%) compared to methotrexate monotherapy.
34761170 Browning of adipose tissue and increased thermogenesis induced by Methotrexate. 2021 Nov Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis due to its well-known anti-inflammatory role in immune cells but its impact on brown and beige adipose tissue biology has not yet been investigated. Here, we present the novel evidence that MTX treatment increases the gene expression of thermogenic genes in brown and beige adipose tissues in a fat cell autonomous manner. Furthermore, we show that treatment of mice with MTX is associated with cold resistance, improved glucose homeostasis, decreased inflammation, and reduced hepatosteatosis in high-fat diet states. Overall, our data provide novel evidence of a role of MTX on thermogenic tissues not previously appreciated.
34584936 Treatment with TNF-α inhibitors versus methotrexate and the association with dementia and 2021 INTRODUCTION: Peripheral inhibition of tumor necrosis factor (TNF)-α, outside of the central nervous system, may result in clinical improvement of Alzheimer's disease (AD) outcomes. TNF-α inhibitors (TNFIs) are effective treatments for various autoimmune conditions and may be effective for preventing and/or treating AD. The objective of this study was to compare the risk of dementia and AD in patients initiating methotrexate versus those initiating TNFIs. METHODS: Insurance claims data from databases of commercially insured and Medicare-eligible patients were used to estimate the risk of dementia and AD within patients with rheumatoid arthritis (RA) initiating a TNFI versus initiation of methotrexate. A sensitivity analysis included all patients without the RA diagnosis requirement. The at-risk period spanned from the index date until a diagnosis of the outcome, loss-to-follow-up, or receipt of the comparator drug. Patients were matched 1-to-1 using propensity scores. A Cox proportional hazards model was used to estimate the hazard ratio (HR). Negative controls were used to calibrate the results. RESULTS: A total of 11,092 new TNFI patients and 44,023 new methotrexate patients were identified, and 8925 from each group were matched. The outcome of dementia occurred in 1.4% of patients in both groups. The calibrated results from the Cox regression found no difference between the two groups (commercially insured database: calibrated HR = 0.69, 95% confidence interval = 0.45 to 1.05; Medicare-only database: 1.14, 0.66 to 1.96). Results were similar in all sensitivity analyses: outcome of AD and including patients without RA. DISCUSSION: No significant difference for the risk of dementia or AD was seen between patients initiating a TNFI versus methotrexate. Although this study cannot conclude whether use of TNFIs is protective against dementia and AD compared with receiving no treatment, there was no evidence that it is more protective than the active comparator methotrexate.
34115645 TNF-α inhibition in the setting of undiagnosed HIV infection: a call for enhanced screeni 2021 Nov 1 BACKGROUND: Despite the risks of immunosuppression, recommendations regarding screening for HIV infection prior to initiation of biologic therapies targeting common rheumatologic disorders, including inflammatory bowel disease (IBD) and inflammatory arthritides, are limited. Few cases of patients started on biologics while living with undiagnosed HIV infection have been reported. METHODS: We report three cases of patients initiated on biologics in the absence of recent or concurrent HIV screening who developed refractory disease or unanticipated complications and were later found to have undiagnosed chronic HIV infection. RESULTS: In Case 1, a 53-year-old MSM with negative HIV testing 2 years prior presented with presumed rheumatoid arthritis. He did not respond to methotrexate, so adalimumab was started. HIV testing to evaluate persistent symptoms was positive 9 months later; CD4+ T-cell count was 800 cells/μl. Antiretroviral therapy (ART) resulted in resolution of symptoms, which were attributed to HIV-associated arthropathy. In Case 2, a 55-year-old woman with injection drug use in remission and no prior HIV testing presented with hidradenitis suppurativa. She started infliximab and methotrexate therapy with good response. After she developed weight loss and lymphopenia, an HIV test was positive; CD4+ T-cell count was 334 cells/μl. Biologic hidradenitis suppurativa therapy was discontinued, with subsequent poor hidradenitis suppurativa control. In Case 3, a 32-year-old MSM with no prior HIV testing presented with presumed IBD; infliximab and steroids were started. Symptoms progressed despite IBD-directed therapy, and he was diagnosed with extensive Kaposi sarcoma with visceral and cutaneous involvement, likely exacerbated by immunosuppression. HIV testing was positive; CD4+ T-cell count was 250 cells/μl. Kaposi sarcoma initially worsened due to ART-associated immune reconstitution inflammatory syndrome. He is now improving with systemic chemotherapy and ART. HIV-associated Kaposi sarcoma is presumed to be the underlying diagnosis. CONCLUSION: All three patients had elevated risk for HIV infection, and two had final diagnoses attributed to chronic HIV infection, not warranting therapeutic immunosuppression. Screening for HIV infection prior to initiation of biologic therapy should be incorporated into clinical practice guidelines.
33856545 Does methotrexate have no beneficial effect in reducing flares in the treatment of polymya 2021 Jul We read the article by Marsman et al. regarding the efficacy of methotrexate (MTX) in the treatment of polymyalgia rheumatica (PMR) with great interest. This study added new insights regarding the use of MTX in a real-world clinical setting and its effect on the incidence rates of flares. However, we would like to voice our concerns regarding the definition of the participants and interventions that were performed in the study, as well as the comparability of the intervention and control groups. Our concerns include the possibility of the inadvertent enrollment of patients with rheumatoid arthritis in a study on PMR, a lack of a clear definition of glucocorticoid ineffectiveness, a lack of adjustment of glucocorticoid dosages, and a reliance on the judgement of individual medical providers rather than clearly defined investigative guidelines in the study procedures. To summarize, we would like to voice concerns about how and to whom MTX was prescribed, as well as the definition of the control group. These revisions and modifications would clarify the importance of the results regarding the efficacy of MTX administration in the treatment of PMR.
34394873 Ankylosing Spondylitis. 2021 Jul The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn's disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral non-granulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF-α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of under-treatment.
34767764 Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdraw 2021 Nov 27 BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA). METHODS: This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434. FINDINGS: Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 [29%] of 72 patients) than with placebo (37 [53%] of 70 patients; hazard ratio 0·46, 95% CI 0·27-0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study. INTERPRETATION: The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections. FUNDING: Pfizer.
34418682 Autoimmune diseases in patients undergoing percutaneous coronary intervention: A risk fact 2021 Sep BACKGROUND AND AIMS: Despite the relation between autoimmune diseases and increased atherosclerotic risk is established, the influence of autoimmune disorders on in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is only partly known. ISR is an aberrant reparative process mainly characterized by an increased number of vascular smooth muscle cells and excessive deposition of extracellular proteoglycans and type III collagen. Chronic inflammation, always present in autoimmune diseases, modulates the endothelial response to PCI. Aim of this review is to resume the current evidence on the association between ISR and autoimmune diseases, focusing on pathogenic mechanisms and therapeutic targets. METHODS: We conducted a comprehensive review of the literature on the relationship between ISR and insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid-antibodies syndrome (APS), inflammatory bowel diseases (IBD), and Hashimoto's thyroiditis (HT). RESULTS: Patients affected with IDDM, RA, SLE, APS, IBD and HT proved to face higher rates of ISR compared to the general population. The endothelial dysfunction seems the principal common pathogenic pathway for ISR and is attributed to both the immune system disorder and the systemic inflammation. Some evidence suggested that methotrexate and anti-tumor necrosis factor treatments can be effective in reducing ISR, while antibodies against vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 showed to reduce neointimal hyperplasia in animal models. CONCLUSIONS: Autoimmune diseases are a risk factor for ISR. The study of the potential cardiovascular benefits of the current therapies, mainly anti-inflammatory drugs, and the pursuit of innovative treatments appear of paramount interest.
33527325 Sjögren's Syndrome Associated with Chikungunya Infection: A Case Report. 2021 Mar Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS.
33443168 Spinal and paraspinal inflammatory reactions after epidural steroid injection in a patient 2021 Apr BackgroundDisease-modifying anti-rheumatic drugs (DMARDs) are used in the management of rheumatoid arthritis (RA) and are classified as conventional DMARDs and biologic agents. A concern with DMARDs is the increased risk of infection after surgery. A practice advisory from the American Society of Anesthesiologists recommend alternatives to neuraxial injections in patients who are immunocompromized. We describe a patient who was on several DMARDs and developed inflammatory reactions in her bilateral paraspinal muscles and lumbar spine after an epidural steroid injection (ESI). CASE PRESENTATION: The patient was a 79-year-old woman; she was taking methotrexate, adalimumab and prednisone for her RA. She had a left L5-S1 paramedian ESI for her L5 radiculitis. After relief of her back and radicular pain for 5 weeks, she had an acute exacerbation of her back pain. MRI showed bilateral paraspinal fluid accumulations and enhancement in her ligamentum flavum. Cultures of the aspirated fluid and biopsy specimens were negative for fungal, aerobic and anaerobic organisms. A repeat MRI 2 months later showed diminution of the fluid collection but with a new fluid accumulation near the left L4-5 facet and left L4 pedicle. Repeat cultures and gram stain of the specimens taken from the pedicle and the paraspinal muscles were negative. The patient was followed by her rheumatologist and in the pain clinic until resolution of her symptoms. CONCLUSIONS: Several society guidelines recommend the continuation of methotrexate but stoppage of the biologic DMARDS before surgery. The occurrence of an intense inflammatory reaction after an ESI in our patient calls for additional research on the subject and shared decision-making between the pain physician, patient and rheumatologist especially in patients on several DMARDs.
34696259 Humoral Response to SARS-CoV-2 Vaccine of a Patient Receiving Methotrexate Treatment and I 2021 Oct 9 We report a case of monitoring the antibody response to the BioNTech-Pfizer vaccine of a 50-year-old female diagnosed with rheumatoid arthritis undergoing treatment with methotrexate (MTX). Antibody levels were measured 21 days after dose 1 (i.e., on the day of dose 2) and then 8, 14 and 30 days after dose 2 with Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics). Patient showed a negative result after dose 1 and had the serum sample retested using a LIAISON(®) SARS-CoV-2 TrimericS IgG assay (DiaSorin), which showed a positive result. Subsequent samples were tested using both assays. Antibody levels kept increasing but at a much slower rate than in patients not receiving any immunomodulatory therapies. Other research indicates that among patients with autoimmune diseases, those receiving disease-modifying antirheumatic drugs (DMARDs) have higher COVID-19 mortality than those treated with tumor necrosis factor inhibitors (TNFis). These results indicate the need for people with autoimmune diseases to be carefully observed following vaccinations, including testing of antibody levels, and treated as potentially at risk until the effect of vaccination is confirmed. The different available vaccines should also be tested to verify their usefulness in the case of people with autoimmune diseases and those who take different immunomodulatory medications.
34511544 Increased MYC expression without MYC gene translocation in patients with the diffuse large 2021 Post-transplant lymphoproliferative disorder (PTLD) and other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are iatrogenic lymphoproliferative disorders (LPD) that develop in association with immunosuppressive treatment in the setting of organ transplantation and autoimmune disease, respectively. Each has a spectrum of pathologies ranging from lymphoid hyperplasia to lymphoma. To clarify the characteristics of the diffuse large B-cell lymphoma (DLBCL) subtype in a cohort of 25 patients with PTLD or OIIA-LPD from our institute, we selected 13 with a histological subtype of DLBCL, including 2 cases of PTLD and 11 of OIIA-LPD. The median patient age at diagnosis was 70 years, with a female predominance. Both PTLD cases developed after kidney transplant. Of the patients with OIIA-LPD, 10 had rheumatoid arthritis, 1 had mixed connective tissue disease, and 8 were treated using methotrexate. Both of the PTLD patients and 6 of the OIIA-LPD patients had extranodal manifestations. All patients except for one were classified as having the non-germinal center B-cell (non-GCB) subtype according to the Hans algorithm. Tissue samples from 8 patients were positive for CD30 and 8 were positive for Epstein-Barr virus (EBV)-encoded small RNA. Seven patients had MYC-positive tissue samples, but none had MYC translocation. Our study suggests that extranodal manifestations and the non-GCB subtype are common, that EBV is associated with the DLBCL subtype of PTLD and OIIA-LPD, and that anti-CD30 therapy is applicable. In addition, our patients with the DLBCL subtype of PTLD and OIIA-LPD exhibited MYC overexpression without MYC translocation, suggesting an alternative mechanism of MYC upregulation.
33601137 Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enone 2021 Apr Four series of double-ring conjugated enones were designed, synthesized and studied for the inhibition of synovial cell activity through the modification of Dysodensiol K core structure, double-ring, double-bond and double-carbonyl groups. For in vitro synovial cell assay of rats, compound 151 and 168 exhibited good inhibitory activities, with IC(50) values of 2.71 ± 0.18 and 2.68 ± 0.16 μM respectively. At the same time, the LDH release and LD(50) test results revealed that the target compounds were low cytotoxicity and acute toxicity. For in vivo CIA model test through the oral administration, compounds 151 and 168 were exhibited similar effect to positive control group methotrexate.
34035003 Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated i 2021 Oct OBJECTIVE: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. RESULTS: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. CONCLUSIONS: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.
33320276 Methotrexate Use for Patients with Psoriasis and Risk of Cutaneous Squamous Cell Carcinoma 2021 Jan 5 An association between methotrexate use and risk of cutaneous squamous cell carcinoma has been reported in patients with rheumatoid and psoriatic arthritis. A nested case-control study was performed to investigate if methotrexate use among patients with psoriasis was associated with increased risk of cutaneous squamous cell carcinoma. Data were obtained from Swedish registers and included 623 patients with psoriasis and a first cutaneous squamous cell carcinoma from 2010 to 2016. Ten randomly selected patients with psoriasis were matched on age and sex to each case. Among cases, 160 (26%) were ever-users of metho-trexate. The corresponding number among the controls was 1,370 (22%), yielding an unadjusted odds ratio (OR) of 1.23 (95% confidence interval (95% CI) 1.02-1.49); p = 0.034. After adjusting for use of other immunosuppressive drugs the association was close to unity (OR 1.09; 95% CI 0.89-1.34); p = 0.39. The slightly increased risk of cutaneous squamous cell carcinoma associated with methotrexate-exposure in patients with psoriasis does not seem to be associated with metho-trexate, but rather with disease severity, other anti-psoriatic treatments, and ultraviolet exposure.
34706401 Methotrexate related cutaneous adverse drug reactions: a systematic literature review. 2021 Oct 27 OBJECTIVES: Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. METHODOLOGY: An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. RESULTS: 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78 years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. CONCLUSIONS: Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. PROSPERO REGISTRATION NUMBER: CRD42020220038.
33916057 Impact of Different JAK Inhibitors and Methotrexate on Lymphocyte Proliferation and DNA Da 2021 Apr 1 Janus kinase inhibitors (JAKis) represent a new strategy in rheumatoid arthritis (RA) therapy. Still, data directly comparing different JAKis are rare. In the present in vitro study, we investigated the immunomodulatory potential of four JAKis (tofacitinib, baricitinib, upadacitinib, and filgotinib) currently approved for RA treatment by the European Medicines Agency. Increasing concentrations of JAKi or methotrexate, conventionally used in RA therapy, were either added to freshly mitogen-stimulated or preactivated peripheral blood mononuclear cells (PBMC), isolated from healthy volunteers. A comparable, dose-dependent inhibition of lymphocyte proliferation was observed in samples treated with tofacitinib, baricitinib, and upadacitinib, while dosage of filgotinib had to be two orders of magnitude higher. In contrast, antiproliferative effects were strongly attenuated when JAKi were added to preactivated PBMCs. High dosage of upadacitinib and filgotinib also affected cell viability. Further, analyses of DNA double-strand break markers γH2AX and 53BP1 indicated an enhanced level of DNA damage in cells incubated with high concentrations of filgotinib and a dose-dependent reduction in clearance of radiation-induced γH2AX foci in the presence of tofacitinib or baricitinib. Thereby, our study demonstrated a broad comparability of immunomodulatory effects induced by different JAKi and provided first indications, that (pan)JAKi may impair DNA damage repair in irradiated PBMCs.