Concomitant Use Of Methotrexate Research Articles

Progressive multifocal leukoencephalopathy reports in rheumatoid arthritis concerning different treatment patterns-an exploratory assessment using the food and drug administration adverse event reporting system

Introduction: Progressive multifocal leukoencephalopathy (PML) is a rare but potentially life-threatening brain infection caused by the John Cunningham virus. PML is a known adverse effect associated with molecular-targeted drugs and immunosuppressive agents. Recent concerns have emerged regarding the link between methotrexate (MTX) and PML. However, limited information exists on the influence of concomitant drug use in rheumatoid arthritis (RA) treatment, where various medications are often used together.Methods: To explore treatment patterns and patient background that affect PML reporting in RA, we analyzed data on RA cases from the Food and Drug Administration Adverse Event Reporting System (FAERS; JAPIC AERS) database between 1997 and 2019.Results and Discussion: Our analysis revealed significantly elevated crude and adjusted reporting odds ratios (aROR) for MTX, rituximab (RIT), azathioprine, and cyclophosphamide. When considering treatment patterns, the concomitant use of MTX and RIT showed a higher aROR than using MTX or RIT alone. Additional TNF-α inhibitors or glucocorticoids did not increase PML reports. Moreover, male sex and older age were associated with increased PML reports. While limitations are inherent in studies using spontaneous reporting data, our exploratory assessment suggests an association between PML and the combination of MTX and RIT and a higher risk in men and older patients. These findings help enhance our understanding of PML risk factors in the context of RA treatment.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study

ObjectiveTo assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels.MethodsLongitudinal, retrospective and...

Drug-drug interaction assessment based on a large-scale spontaneous reporting system for hepato- and renal-toxicity, and thrombocytopenia with concomitant low-dose methotrexate and analgesics use

BackgroundMethotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment and is highly effective with low-dose intermittent administration. MTX is occasionally used in combination with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP)/paracetamol for pain or inflammation control. With MTX treatment, the side effects, such as hepatotoxicity, renal failure, and myelosuppression should be considered. These are also seen with analgesics treatment.MethodsWe used a large spontaneously reported adverse event database (FAERS [JAPIC AERS]) to analyze whether the reporting of adverse events increased upon MTX and analgesic therapy in patients with RA.ResultsAfter identifying RA cases, the crude reporting odds ratios (cRORs) for hepatotoxicity, renal failure, and thrombocytopenia associated with the use of MTX, APAP, or NSAIDs were calculated by disproportionality analysis, which revealed significantly higher cRORs for these events. No analgesics showed consistent positive signals for drug-drug interaction (DDI) with concomitant low-dose MTX analyzed using four algorithms for DDI interaction (the Ω shrinkage measure, additive or multiplicative, and combination risk ratio models). However, in renal failure and thrombocytopenia, loxoprofen (Ω025 = 0.08) and piroxicam (Ω025 = 0.46), and ibuprofen (Ω025 = 0.74) and ketorolac (Ω025 = 3.52), respectively, showed positive signals in the Ω shrinkage measure model, and no consistency was found among adverse events or NSAIDs.ConclusionsStudies using spontaneous reporting systems have limitations such as reporting bias or lack of patient background; however, the results of our comprehensive analysis support the results of previous clinical or epidemiological studies. This study also demonstrated the usefulness of FAERS for DDI assessment.

Comparative Effectiveness of Bimekizumab in Psoriatic Arthritis: A Model-Based Meta-Analysis of American College of Rheumatology Response Criteria.

A model-based meta-analysis (MBMA) was conducted to compare the efficacy of bimekizumab with other psoriatic arthritis (PsA) treatment regimens using ≥ 20%/50%/70% improvements in American College of Rheumatology (ACR) criteria (ACR20/50/70) for patients with PsA. Forty-nine trials of 16 drugs were identified in the literature, comprising 21,340 patients. Trial-level covariates, including prior biologic use, concomitant methotrexate use, time since diagnosis, trial completion year, and active comparator were considered for exploratory models. The final model was selected using leave-one-out cross-validation (LOO CV) to assess predictive performance based on prespecified criteria. LOO CV was conducted for 15 trials; the final model demonstrated that 91.5% (952/1,040) of the observed treatment differences, and 96.1% of the observed ACR20/50/70 response rates were within the 95% prediction interval (PI). Median ACR50 response rates (95% PI) at week 16 in biologic-naïve patients were predicted to be 44% (40-49%) for bimekizumab 160 mg, among the highest of all treatments analyzed. Response rates for secukinumab 150 mg and risankizumab 150 mg were 28% (25-32%) and 27% (24-31%), respectively. The MBMA was also used to predict the probability of success (PoS) of potential head-to-head trials using ACR50 response as the end point with varying sample sizes: vs. secukinumab 150 mg, the PoS for bimekizumab 160 mg was 62% (N = 200) and 90% (N = 400). Versus risankizumab 150 mg, the PoS for bimekizumab 160 mg was 68% (N = 200) and 94% (N = 400). In summary, a predictive MBMA described ACR20/50/70 outcomes in PsA, allowing accurate and precise treatment comparisons and robust PoS calculations.

Population Pharmacokinetics of Ozoralizumab in Patients with Rheumatoid Arthritis.

Ozoralizumab is a bispecific NANOBODY compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin. Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its human serum albumin-binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis in Phase II/III and Phase III trials to assess the effects of potential PK covariates. The ozoralizumab PK after subcutaneous administration was described using a 1-compartment model with first-order absorption and first-order elimination processes. A proportional error model was used for inter- and intra-individual variabilities, with covariance set between inter-individual variabilities of the apparent clearance and apparent distribution volume. Body weight, sex, antidrug antibody status, estimated glomerular filtration rate, and concomitant methotrexate use were identified as covariates for apparent clearance, while body weight and sex were covariates for apparent distribution volume in the final model. Body weight had the greatest effect on the PK of ozoralizumab, while the other covariates had minor effects. When administered at 30 mg every 4 weeks, the predicted steady-state plasma trough concentration in a patient weighing 83.2 kg exceeded the trough concentration required to maintain efficacy of ozoralizumab, and the estimated exposure in a patient weighing 42.5 kg did not exceed the mean exposure at 80 mg, a well-tolerated dose, throughout 52 weeks. We developed a population PK model that adequately described the ozoralizumab PK in Japanese patients with rheumatoid arthritis, and none of the evaluated covariates showed clinically relevant effects on the PK of ozoralizumab.

Quantifying the Effect of Methotrexate on Adalimumab Response in Psoriasis by Pharmacokinetic–Pharmacodynamic Modeling

Previously, we showed that the combination of methotrexate and adalimumab treatment leads to less antidrug antibody development. In this study, we quantify the pharmacokinetics/pharmacodynamics (PK/PD) of adalimumab and evaluate the influence of methotrexate cotreatment. A population PK-PD model was developed using prospective data from 59 patients with psoriasis (baseline PASI= 12.6) receiving adalimumab over 49 weeks. Typical PK and PD parameters and their corresponding interpatient variability were estimated. We performed a covariate analysis to assess whether interpatient variability could be explained by addition of methotrexate and other covariates. In total, 330 PASIs, 252 adalimumab serum concentrations, and 247 antidrug antibody titers were available. Presence of antidrug antibodies (adalimumab group= 46.7%, adalimumab+ methotrexate group= 38.7%; P= .031) was correlated with increased adalimumab apparent clearance (P < .001). In the PD model, the use of concomitant methotrexate was borderline to significantly correlated with a decreased half-maximal inhibitory concentration (adalimumab concentration for which clinical response score is reduced by half; P < .10). On the basis of our PK-PD model, concomitant use of methotrexate indirectly increases adalimumab concentration, partially through less antidrug antibodies formation, which may result in better efficacy.

Intra-amniotic and systemic administration of methotrexate with concomitant surgical evacuation of 11 + 5 weeks cervical ectopic pregnancy: a case report

BackgroundCervical pregnancy is a rare type of ectopic pregnancy. The management of cervical pregnancy is challenging because of the rarity of the condition, late presentation, which is associated with increased risk of failed medical treatment, and excessive post-evacuation bleeding that may require hysterectomy. There is no good evidence in the literature regarding the pharmacological management of living cervical ectopic pregnancy of more than 9 + 0 weeks of gestation, and there is no standard protocol on methotrexate doses in these cases.Case presentationWe present this case to describe a concomitant medical and surgical management of a living 11 + 5 weeks cervical pregnancy. The initial beta-human chorionic gonadotropins (ß-hCG) serum level was 108,730 IU/L. The patient received 60 mg of methotrexate intra-amniotically followed by another dose of 60 mg of methotrexate intramuscularly 24 h later. Fetal heartbeats stopped on day 03. On day 07, the ß-hCG was 37,397 IU/L. On day 13, the patient had evacuation of the remaining products of conception with the insertion of an intracervical Foley catheter to minimize the bleeding. On day 34, the ß-hCG was negative.ConclusionThe concomitant use of methotrexate to induce fetal demise along with surgical evacuation may be considered in the management of advanced cervical pregnancy to avoid excessive blood loss, and ultimately hysterectomy.

OA02 Real-world experience of dose tapering TNF inhibitors in rheumatoid arthritis: Long-term results

Abstract Background/Aims If sustained disease control is achieved in RA then tapering is supported by recommendations. However, this may cause loss of disease control with subsequent damage. A problem in assessing tapering is the short-term nature of studies. We wanted to explore the long-term use of tapering strategies. Methods Our biologics database has collected information since 2005. Our approach, refined with PPI, for people receiving TNF inhibitors (TNFi) has been to dose taper by one-third and then 50% if remission was achieved (DAS28&amp;lt;2.6 on 2 occasions &amp;gt;6 months apart, no corticosteroids). We initially required absence of power doppler (PD) in the hands (stopped in 2017). Failure of tapering was defined as a flare (DAS28&amp;gt;2.6, PD synovitis or patient-reported) resulting in a return to full dose, stopping the TNFi, or changing to another advanced therapy (bDMARD, tsDMARD). We explored associations between time on dose-reduction therapies and individual characteristics. Results 1180 patients started biological therapies during 2005-2021 with 668 receiving a TNFi. 119 (18%) were dose-tapered by one-third and of these 40 (30%) then by one-half. Over median follow-up of 2.2 years (IQR 0.7,5.9) with maximum follow-up of 8.93 years, tapering failed in 88 (74%). Of those failing, 50% achieved DAS28 remission, 18% low disease activity (LDA), 32% moderate (MDA) and none high (HDA) within 12 months. A Kaplan-Meier plot showed one-third of individuals failed tapering within the first year with two-thirds by 3 years. Logistic regression showed (Table 1) no significant effect of age, sex, time between diagnosis and TNFi, seropositivity, smoking, or DAS28 score. However, there was an association between concomitant use of methotrexate and reduced failure of tapering (HR 0.60 (CI 0.39,0.94) p = 0.03). Conclusion In a real-world setting, tapering is well accepted and occurred in around 20% of individuals. Two-thirds maintain tapering after 1 year with around one-third by 3 years. Predictors of success are limited although concurrent methotrexate use appears associated with continued tapering. However, around a third of patients who fail tapering do not return to remission/LDA when the full dose of TNFi is restarted. Disclosure M. Lwin: None. N. Nooh: None. C.R. Holroyd: Member of speakers’ bureau; Abbvie, BMS, Celltrion, Chugai, Galapagos/Gilead, Janssen, Lilly, Napp, Novartis, Pfizer, Roche and UCB. Other; Sponsorship / advisory board: Abbvie, BMS, Celltrion, Chugai, Galapagos/Gilead, Janssen, Lilly, Napp, Novartis, Pfizer, Roche and UCB. S.X. Lin1: None. D. Culliford: None. S.D. Fraser: None. C.J. Edwards: Member of speakers’ bureau; Abbvie, Astra Zeneca, BMS Celltrion Chugai, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sandoz, Samsung. Grants/research support; Abbvie, Astra Zeneca, BMS Celltrion Chugai, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sandoz, Samsung. Other; Advisory boards: Abbvie, Astra Zeneca, BMS Celltrion Chugai, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sandoz, Samsung.

Evaluation of Adverse Drug Reaction Caused by Concomitant Use of Trimethoprim-Sulfamethoxazole and Methotrexate in Pediatric Acute Lymphoblastic Leukemia Patients

Evaluation of Adverse Drug Reaction Caused by Concomitant Use of Trimethoprim-Sulfamethoxazole and Methotrexate in Pediatric Acute Lymphoblastic Leukemia Patients

Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial

Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of increased adalimumab dose intervals versus conventional dosing in patients with Crohn's disease in stable remission. The LADI study was a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial, done in six academic hospitals and 14 general hospitals in the Netherlands. Adults (aged ≥18 years) diagnosed with luminal Crohn's disease (with or without concomitant perianal disease) were eligible when in steroid-free clinical and biochemical remission (defined as Harvey-Bradshaw Index [HBI] score <5, faecal calprotectin <150 μg/g, and C-reactive protein <10 mg/L) for at least 9 months on a stable dose of 40 mg subcutaneous adalimumab every 2 weeks. Patients were randomly assigned (2:1) to the intervention group or control group by the coordinating investigator using a secure web-based system with variable block randomisation (block sizes of 6, 9, and 12). Randomisation was stratified on concomitant use of thiopurines and methotrexate. Patients and health-care providers were not masked to group assignment. Patients allocated to the intervention group increased adalimumab dose intervals to 40 mg every 3 weeks at baseline and further to every 4 weeks if they remained in clinical and biochemical remission at week 24. Patients in the control group continued their 2-weekly dose interval. The primary outcome was the cumulative incidence of persistent flares at week 48 defined as the presence of at least two of the following criteria: HBI score of 5 or more, C-reactive protein 10 mg/L or more, and faecal calprotectin more than 250 μg/g for more than 8 weeks and a concurrent decrease in the adalimumab dose interval or start of escape medication. The non-inferiority margin was 15% on a risk difference scale. All analyses were done in the intention-to-treat and per-protocol populations. This trial was registered at ClinicalTrials.gov, NCT03172377, and is not recruiting. Between May 3, 2017, and July 6, 2020, 174 patients were randomly assigned to the intervention group (n=113) or the control group (n=61). Four patients from the intervention group and one patient from the control group were excluded from the analysis for not meeting inclusion criteria. 85 (50%) of 169 participants were female and 84 (50%) were male. At week 48, the cumulative incidence of persistent flares in the intervention group (three [3%] of 109) was non-inferior compared with the control group (zero; pooled adjusted risk difference 1·86% [90% CI -0·35 to 4·07). Seven serious adverse events occurred, all in the intervention group, of which two (both patients with intestinal obstruction) were possibly related to the intervention. Per 100 person-years, 168·35 total adverse events, 59·99 infection-related adverse events, and 42·57 gastrointestinal adverse events occurred in the intervention group versus 134·67, 75·03, and 5·77 in the control group, respectively. The individual benefit of increasing adalimumab dose intervals versus the risk of disease recurrence is a trade-off that should take patient preferences regarding medication and the risk of a flare into account. Netherlands Organisation for Health Research and Development.

Persistence and Safety of Golimumab in Elderly Patients with Rheumatoid Arthritis and Renal Dysfunction in a Real-World Setting.

The efficacy and safety of golimumab in elderly patients with renal dysfunction are not well evaluated due to the exclusion criteria of clinical trials. To assess the persistence and safety of golimumab in elderly rheumatoid arthritis patients with renal dysfunction. In this retrospective observational study, we used Japan's nationwide electronic medical records and claims database to identify patients aged 65years and older who were newly prescribed golimumab for rheumatoid arthritis between July 2011 and June 2018. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR; high, ≥ 90; moderate, ≥ 60, < 90; low, ≥ 30, < 60), and the persistence of golimumab and adverse events were compared between the groups. A total of 423 patients met the eligibility criteria. At 6 months, the persistence rates of golimumab were 62.4%, 63.7% and 67.0% in the high, moderate and low eGFR groups, respectively. In Cox proportional hazards regression analysis, baseline eGFR was not associated with golimumab persistence or adverse events, but concomitant methotrexate and low baseline C-reactive protein (CRP) were associated with longer golimumab persistence. Reduced renal function was not associated with continuation of golimumab or incidence of adverse events, suggesting that the persistence of golimumab therapy in patients with rheumatoid arthritis is independent of the baseline level of renal function. On the other hand, concomitant use of methotrexate and low baseline CRP levels were suggested as factors that may affect the persistence of golimumab treatment.

Comparing the effectiveness and safety of Abatacept and Tocilizumab in elderly patients with rheumatoid arthritis.

The number of biological DMARDs (bDMARDs) used in elderly patients with rheumatoid arthritis (RA) has increased in recent years. We aimed to compare the drug retention rates and safety of abatacept (ABT) and tocilizumab (TCZ) in elderly patients with RA. A total 125 elderly patients with RA (>65 years) who began therapy with either ABT (n = 47) or TCZ (n = 78) between 2014 and 2021 at our institute were enrolled. We compared the drug retention rate and clinical response at 24 weeks between elderly patients with RA treated with ABT and those treated with TCZ. Adverse events (AEs) and the reasons for drug discontinuation were assessed. There was no significant difference in demographic characteristics except for the use of glucocorticoid between the ABT and TCZ groups. There was no significant difference in the drug retention rate between the ABT and TCZ groups. Furthermore, there was no significant difference in the discontinuation rates due to the lack of effectiveness between these two groups. The proportions of the patients archiving low disease activity at 24 weeks did not differ significantly between the two groups. Whereas, the discontinuation rates due to AEs, including interstitial lung disease (ILD), seemed higher in the TCZ group than in the ABT group. In TCZ-treated group, the concomitant use of methotrexate (MTX) significantly increased the incidences of AEs leading to the discontinuation of TCZ. Whereas these was no significant impact of concomitant use of MTX on the incidences of AEs leading to discontinuation in ABT-treated group. In elderly patients with RA treated with ABT and TCZ, drug retention rates were equivalent between the two groups. There were some differences in safety profiles between ABT and TCZ, and the rates of discontinuation due to AEs, including ILD, seem to be lower with ABT than with TCZ in elderly patients with RA.

Unincreased risk of hospitalized infection under targeted therapies versus methotrexate in elderly patients with rheumatoid arthritis: a retrospective cohort study

BackgroundInfection is one of the primary concerns during treatment for rheumatoid arthritis (RA) in elderly patients. However, infection risk of patients with RA receiving targeted therapy (TT) including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKIs) in elderly patients are scarce. The aim of this study was to compare the risk of hospitalized infection (HI) with TT versus methotrexate (MTX) therapy among young, elderly, and older elderly patients with RA.MethodsUsing Japanese claims data, patients satisfying the following criteria were enrolled: (1) ≥ one ICD10 code for RA; (2) ≥ one prescription of MTX or TT (bDMARDs and JAKIs) between April 2008 and September 2018; and (3) ≥16 years old. We calculated the incidence rate (IR) of HI per 100 patient-years in the young, elderly, and older elderly groups (those aged 16–64, 65–74, and ≥75 years, respectively) and the IR ratio (TT vs. MTX) of HI. A logistic regression model was used to estimate the associations between HI and TT versus MTX in each group.ResultsThe overall IR of HI per 100 patient-years (95% confidence interval) was 3.2 [2.9–3.5], 5.0 [4.6–5.4], and 10.1 [9.5–10.9] in the young, elderly, and older elderly groups, respectively. Concomitant use of MTX or immunosuppressive DMARDs with TT was less frequent in the elderly and older elderly groups. The adjusted odds ratio of TT vs. MTX for HI was 1.3 (1.0–1.7; p = 0.021), 0.79 (0.61–1.0; p = 0.084), and 0.73 (0.56–0.94; p = 0.015) in the young, elderly, and older elderly groups, respectively.ConclusionThe overall IR of HI was increased with age. The risk of HI under TT compared to MTX was not elevated in elderly and older elderly patients after adjusting for patients’ characteristics and concomitant treatments.

Efficacy and safety of ixekizumab in patients with active psoriatic arthritis with and without concomitant conventional disease-modifying antirheumatic drugs: SPIRIT-P1 and SPIRIT-P2 3-year results

Introduction/objectivesTo evaluate the three-year efficacy and safety of ixekizumab with and without concomitant conventional synthetic disease-modifying antirheumatic drug (csDMARD) use in patients with active psoriatic arthritis (PsA).MethodPatients with PsA who were biologic-naïve (SPIRIT-P1, NCT01695239) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2, NCT02349295) were randomized to receive 80-mg ixekizumab every four weeks after receiving 160-mg ixekizumab at baseline. Efficacy, safety, and immunogenicity were evaluated in this post-hoc analysis in three subgroups: (1) ixekizumab monotherapy, (2) ixekizumab and methotrexate (MTX), (3) ixekizumab and any csDMARD (including MTX). Missing data were imputed using multiple imputation for continuous variables and modified non-responder imputation for categorical variables.ResultsEfficacy was similar across the three subgroups with 59.1%, 67.0%, and 66.1% of ixekizumab-treated patients achieving 20% improvement in the American College of Rheumatology scale score at week 156. Radiographic progression of structural joint damage (SPIRIT-P1 only) was similarly inhibited across the three subgroups with several outliers. No new safety signals were reported, and 91.0%, 84.1%, and 83.2% in the three subgroups reported ≥ 1 treatment-emergent adverse event. At week 156, 15.9%, 13.1%, and 11.0% in the three subgroups had antidrug antibodies; most had low titer status.ConclusionsIxekizumab showed sustained efficacy in treating patients with PsA for up to three years in monotherapy or in combination with MTX or any csDMARD. The three subgroups had similar safety and immunogenicity profiles, which supports that the use of concomitant MTX or csDMARDs does not seem to impact the benefit/risk profile of ixekizumab.Key Points• Ixekizumab treatment led to improved clinical responses over time when used as monotherapy or in combination with concomitant MTX or any concomitant csDMARD (including MTX) in patients with active PsA.• Ixekizumab monotherapy has similar radiographic efficacy as ixekizumab with MTX or ixekizumab with other csDMARDs (including MTX); similar inhibition of radiographic progression was observed between the subgroups of patients receiving ixekizumab monotherapy or ixekizumab with MTX or other csDMARDs.• The long-term safety profile of ixekizumab used as monotherapy or in combination with MTX or any other csDMARDs is consistent with what has been previously reported. The addition of MTX or any csDMARD to ixekizumab treatment did not negatively impact the favorable long-term safety profile of ixekizumab.

Influence of concomitant methotrexate use on the clinical effectiveness, retention, and safety of abatacept in biologic-naïve patients with rheumatoid arthritis: Post-hoc subgroup analysis of the ORIGAMI study.

We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naïve patients with rheumatoid arthritis. Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Do JAK inhibitors affect immune response to COVID-19 vaccination? Data from the MAJIK-SFR Registry.

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use.

ObjectiveTo describe risk factors for IBD development in a cohort of children with JIA.MethodsJIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR).ResultsOut of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89).ConclusionIBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

Ultrasound efficacy of targeted-synthetic disease-modifying anti-rheumatic drug treatment in rheumatoid arthritis: a multicenter prospective cohort study in Japan

Objective This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient characteristics and previous treatments. Method This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups. Results All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders. Conclusion Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

German S3-Guideline on the treatment of Psoriasis vulgaris, adapted from EuroGuiDerm - Part 2: Treatment monitoring and specific clinical or comorbid situations.

Contribution of a European-Prevalent Variant near CD83 and an East Asian-Prevalent Variant near IL17RB to Herpes Zoster Risk in Tofacitinib Treatment: Results of Genome-Wide Association Study Meta-Analyses.

ObjectiveTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis, and has been previously investigated for psoriasis (PsO). This meta‐analysis of genome‐wide association studies (GWAS) was performed to identify genetic factors associated with increased risk/faster onset of herpes zoster (HZ) in subjects with RA or PsO receiving tofacitinib treatment, and to determine potential mechanisms that could be attributed to the varying rates of HZ across ethnicities.MethodsIn an ethnicity/indication‐specific, trans‐ethnic, trans‐population meta‐analysis of GWAS in subjects with RA or PsO from phase II, phase III, and long‐term extension studies of tofacitinib, 8 million genetic variants were evaluated for their potential association with time to an HZ event and incidence of an HZ event (case versus control) with tofacitinib treatment, using Cox proportional hazard and logistic regression analyses, respectively.ResultsIn total, 5,246 subjects were included (3,168 with RA and 2,078 with PsO). After adjustment for age, baseline absolute lymphocyte count, genetically defined ethnicity, and concomitant methotrexate use (in RA subjects only), 4 loci were significantly associated with faster onset of HZ in European subjects (P < 5 × 10−8), including a single‐nucleotide polymorphism (SNP) near CD83 (frequency of risk allele ~2% in European subjects versus ~0.1% in East Asian subjects). In the trans‐ethnic, trans‐population meta‐analysis, the CD83 SNP remained significant. Four additional significant loci were identified in the meta‐analysis, among which a SNP near IL17RB was associated with faster onset of HZ (meta‐analysis hazard ratio 3.6 [95% confidence interval 2.40–5.44], P = 7.6 × 10−10; frequency of risk allele ~12% in East Asian subjects versus <0.2% in European subjects).ConclusionGenetic analysis of tofacitinib‐treated subjects with RA or PsO identified multiple loci associated with increased HZ risk. Prevalent variants near the immune‐relevant genes CD83 and IL17RB in European and East Asian populations, respectively, may contribute to risk of HZ in tofacitinib‐treated subjects.