Immunogenicity, reactogenicity, and safety of two-dose adjuvanted herpes zoster subunit vaccine in patients with systemic lupus erythematosus in South Korea: a single-centre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: The adjuvanted herpes zoster subunit vaccine has shown good efficacy and safety in the general population. However, its effectiveness has not been comprehensively assessed in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate the immunogenicity and safety of the adjuvanted herpes zoster subunit vaccine in patients with SLE. METHODS: This single-centre, randomised, double-blind, placebo-controlled, trial was done at the rheumatology outpatient clinic at Seoul National University Hospital, South Korea. Patients (aged ≥19 years) with clinically stable SLE and previous exposure (≥4 weeks) to immunosuppressive drugs were randomly assigned (4:1) via a central interactive web response system to receive herpes zoster subunit vaccine or placebo (0·5 mL intramuscular injection) at weeks 0 and 8. Investigators and participants were masked to intervention and group assignment. Anti-glycoprotein E antibody titres and glycoprotein E-specific cell-mediated vaccine responses were evaluated at baseline and at week 8 after the first dose, and at week 4, week 26, and week 52 after the second dose using enzyme-linked immunosorbent assay and flow cytometry, respectively. Reactogenicity, SLE disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rate, were examined. The primary outcome was the proportion of patients with a positive humoral vaccine response 4 weeks after the second dose. The primary and safety analyses were done in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT06001606. FINDINGS: Between June 14, and July 19, 2023, 65 patients with SLE were enrolled, of whom 52 were randomly assigned to the herpes zoster subunit vaccine and 13 to placebo. 49 patients in the vaccine group and 11 patients in the placebo group were included in the modified intention-to-treat population. 56 (93%) of 60 patients were women and four (7%) were men. Mean age was 48·7 years (SD 11·4). The proportion of participants with a humoral vaccine response at 4 weeks after the second dose was significantly higher in the vaccine group (48 [98%] of 49 participants) than the placebo group (none [0%] of 11 patients; p<0·0001). More patients in the vaccine group than placebo group reported injection site reactions (42 patients vs two patients), fever (ten vs none), and fatigue (26 vs two). There were no differences in Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rates between the groups. There were no treatment-related deaths. INTERPRETATION: The herpes zoster subunit vaccine induces humoral and cellular immunity against herpes zoster with a good safety profile in patients with SLE. A larger study is warranted to assess the efficacy of vaccines to prevent herpes zoster in patients with SLE. FUNDING: Ministry of Science and ICT, The Government of the Republic of Korea.

Seronegative patients with primary Sjögren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva.

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.

Successful treatment of hemophagocytic lymphohistiocytosis in a patient with systemic lupus erythematosus with ruxolitinib: a case report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder characterized by uncontrolled activation of CD8+ T and natural killer cells, leading to a cytokine storm and severe organ dysfunction. Although secondary HLH related to autoimmune diseases usually demonstrates a good treatment response to immunosuppressive therapy for underlying conditions, there is no consensus regarding the treatment in case of unresponsiveness to the treatment. Herein, we present a case of HLH that was unresponsive to high-dose glucocorticoid and cyclosporine treatment in a patient with newly diagnosed systemic lupus erythematosus. The patient's clinical features and laboratory abnormalities rapidly improved with ruxolitinib, an oral Janus kinase 1 and 2 (JAK1/2) inhibitor. This result suggests that blocking JAK-STAT pathway may be a potential treatment option in patients with refractory HLH secondary to autoimmune diseases.

Flare prediction after tapering the dose of tumour necrosis factor inhibitors in patients with axial spondyloarthritis: A nationwide cohort study.

OBJECTIVES: To develop a model for predicting flares after tapering the dose of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS: Data were obtained from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. In total, 526 patients who received the standard-dose TNFi for at least 1 year and tapered their dose were included in the derivation cohort. The main outcome was a flare occurrence defined as an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) score of ≥ 2.1 after 1 year of TNFi tapering. The final prediction model was validated using an independent cohort. RESULTS: Among 526 patients, 127 (24.1%) experienced flares. The final prediction model included negative human leucocyte antigen B27 (ß = 1.088), inflammatory back pain (ß = 1.072), psoriasis (ß = 1.567), family history of SpA (ß = 0.623), diabetes mellitus (ß = 1.092), TNFi tapering by ≥ 50% of the standard-dose (ß = 0.435), ASDAS-CRP at tapering (ß = 1.029), and Bath Ankylosing Spondylitis Functional Index score at tapering (ß = 0.194) as covariates. It showed an excellent discrimination performance (AUC = 0.828). According to the predictive risk, patients were classified into three groups (low-, intermediate-, and high-risk). The probabilities of flares in these groups were 4.5%, 18.1%, and 61.8%, respectively. The performance of the model in the validation cohort was also comparable. CONCLUSION: The established prediction model accurately predicted the risk of flares after TNFi dose tapering in patients with axSpA using eight simple clinical parameters, which could be helpful to select appropriate patients for tapering their TNFi without flare in daily clinical practice.

What rheumatologists need to know about mRNA vaccines: current status and future of mRNA vaccines in autoimmune inflammatory rheumatic diseases.

Messenger RNA (mRNA) vaccines as a novel vaccine platform offer new tools to effectively combat both emerging and existing pathogens which were previously not possible. The 'plug and play' feature of mRNA vaccines enables swift design and production of vaccines targeting complex antigens and rapid incorporation of new vaccine constituents as needed. This feature makes them likely to be adopted for widespread clinical use in the future.Currently approved mRNA vaccines include only those against SARS-CoV-2 virus. These vaccines demonstrate robust immunogenicity and offer substantial protection against severe disease. Numerous mRNA vaccines against viral pathogens are in the early to late phase of development. Several mRNA vaccines for influenza are tested in clinical trials, with some already in phase 3 studies. Other vaccines in the early and late phases of development include those targeting Cytomegalovirus, varicella zoster virus, respiratory syncytial virus and Epstein-Barr virus. Many of these vaccines will likely be indicated for immunosuppressed populations including those with autoimmune inflammatory rheumatic diseases (AIIRD). This review focuses on the mechanism, safety and efficacy of mRNA in general and summarises the status of mRNA vaccines in development for common infectious diseases of particular interest for patients with AIIRD.

Current myositis clinical trials and tribulations.

With improved understanding of disease pathogenesis and availability of outcome measures, there has been a remarkable increase in the number of therapeutic clinical trials in idiopathic inflammatory myopathies (myositis) over the last three years reaching as many as five trials per site. These trials share similar design and inclusion/exclusion criteria resulting in a competitive clinical trial landscape in myositis. While these are exciting times for the myositis field, we have a number of concerns about the design and conduct of the myositis trials. These include competitive landscape, lengthy placebo arms, underrepresentation of minority groups among participants, use of patient reported outcome measures with limited/no data on validity in myositis, antiquated disease classification criteria, and unclear performance of the ACR/EULAR Myositis Response Criteria in skin-predominant patients despite inclusion of these patients in trials. In this viewpoint, we further discuss these concerns and offer potential solutions such as including patient perspectives in the trial design and adoption of innovative frameworks.

COVID-19 infection and efficacy of vaccination in patients with rheumatic diseases during Omicron outbreak in South Korea: a prospective cohort study.

OBJECTIVES: This study aims to investigate COVID-19 epidemiological data in patients with autoimmune inflammatory rheumatic diseases (AIRDs) during Omicron wave and to identify clinical factors associated with infection, including COVID-19 vaccination. METHODS: This prospective longitudinal study was performed between January and October 2022 in South Korea. Patients were classified into AIRD and non-AIRD groups according to their underlying diseases. COVID-19 status, date of confirmed infection and vaccination status were captured from the patient survey and national database. The COVID-19 incidence during the study period was examined and compared between the two groups. The effect of clinical factors on the infection rate was analysed in the AIRD group. RESULTS: A total of 1814 patients (1535 and 279 in the AIRD and non-AIRD groups, respectively) were analysed. During the study period, 857 COVID-19 cases were reported in 834 patients (46.0%). The infection rates in the AIRD and non-AIRD groups were comparable. In the AIRD group, older age (≥70 years) and glucocorticoid use were significantly associated with a lower rate of COVID-19 infection. The third booster vaccination significantly lowered the incidence of COVID-19 (adjusted HR 0.85 (95% CI 0.73 to 0.99)), and the prophylactic effect was more evident in patients aged <70 years (0.81 (95% CI 0.69 to 0.95), p value for interaction 0.036). CONCLUSION: The risk of SARS-CoV-2 infection with the Omicron variant did not increase in patients with AIRDs. The third booster vaccination regimen decreased the infection rate in patients aged <70 years.

Physicians' Agreement on and Implementation of the 2019 European Alliance of Associations for Rheumatology Vaccination Guideline: An International Survey.

Objective: To evaluate the perspective of healthcare professionals towards the 2019 European Alliance of Associations for Rheumatology (EULAR) vaccination guideline in patients with autoimmune inflammatory rheumatic diseases (AIIRD). Methods: Healthcare professionals who care for patients with AIIRD were invited to participate in an online survey regarding their perspective on the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD. Level of agreement and implementation of the 6 overarching principles and 9 recommendations were rated on a 5-point Likert scale (1~5). Results: Survey responses of 371 healthcare professionals from Asia (42.2%) and North America (41.6%), Europe (13.8%), and other countries were analyzed. Only 16.3% of participants rated their familiarity with the 2019 EULAR guideline as 5/5 ("very well"). There was a high agreement (≥4/5 rating) with the overarching principles, except for the principles applying to live-attenuated vaccines. There was a high level of agreement with the recommendations regarding influenza and pneumococcal vaccinations; implementation of these recommendations was also high. Participants also reported a high level of agreement with the remaining recommendations but did not routinely implement these recommendations. Conclusion: The 2019 update of EULAR recommendations for the vaccination of adult patients with AIIRD is generally thought to be important by healthcare professionals, although implementation of adequate vaccination is often lacking. Better education of healthcare providers may be important to optimize the vaccination coverage for patients with AIIRD.

Intrinsic contracture of the hands in sarcoid myopathy.

Hand involvement in sarcoidosis is rare and it presents as tenosynovitis, dactylitis, nodules and osteoarticular bony destruction. We describe an unusual presentation of progressive intrinsic muscle contracture of both hands in a 42-year-old woman with sarcoid myopathy who presented with painful swelling and weakness of all four extremities. Her systemic symptoms improved with oral corticosteroids, but the hand muscle contracture remained after resolution of myositis. Serial soft tissue releases of intrinsic muscle contracture improved hand function markedly. This case highlights that surgery is a viable option to treat intrinsic muscle contracture in patients with chronic sarcoid myopathy complicated with severe muscle contracture.

Immunoassay Detects Salivary Anti-SSA/Ro-52 Autoantibodies in Seronegative Patients with Primary Sjögren's Syndrome.

The diagnostic work-up for Sjögren's syndrome is challenging and complex, including testing for serum autoantibodies to SSA/Ro and a labial salivary gland biopsy. Furthermore, the diagnosis is often delayed. In this study, we tested the hypothesis that anti-SSA/Ro autoantibodies are detectable in the saliva of patients with primary Sjögren's syndrome (pSS) because the disease affects the salivary glands, and these autoantibodies display greater discriminatory performance in saliva than in serum. SSA/Ro-52 Ags were used to develop what is, to our knowledge, a novel quantitative electrochemical-based immunoassay: the electric field-induced release and measurement (EFIRM) platform. The clinical utility was determined by measuring salivary anti-SSA/Ro-52 autoantibodies in patients with pSS and sicca (n = 34), patients without pSS with sicca (n = 35), and healthy subjects (n = 41). The statistical analysis of discrimination included the area under the receiver operating characteristic curve. Salivary anti-SSA/Ro-52 autoantibodies were measured in 94% (32 of 34) of patients with pSS with 85% (29 of 34) seropositivity. Four of the five seronegative patients with pSS had EFIRM-measurable anti-SSA/Ro-52 autoantibodies in saliva. Additionally, 60% (21 of 35) of the seronegative patients without pSS who had sicca had EFIRM-detectable SSA/Ro-52 autoantibodies in saliva, indicating the onset of autoimmune disease. Two of the 41 healthy control subjects had EFIRM-detectable SSA/Ro-52 autoantibodies in their saliva. Salivary SSA/Ro-52 autoantibodies significantly discriminated patients with pSS or patients with the initial stage of autoimmune disease from healthy subjects with an area under the receiver operating characteristic curve of 0.91. Our findings suggest that the proposed saliva SSA/Ro-52 immunoassay improves early and accurate diagnosis of seronegative patients with pSS and patients with early-onset autoimmune disease.

Increased risk of congenital malformations in offspring born to women with systemic lupus erythematosus in South Korea: a nationwide population-based study.

OBJECTIVES: The aim of this study was to determine the risk of congenital malformations in offspring born to women with systemic lupus erythematosus (SLE). METHODS: This nationwide population-based study included Korean women who had a singleton pregnancy. The risk of congenital malformations in women with SLE was compared with those without SLE. Multivariable analyses were performed to estimate the OR of congenital malformations. In a sensitivity analysis, the risk of malformation was compared between the offspring of women with SLE and those of propensity-matched women without SLE. RESULTS: Of a total of 3 279 204 pregnant women, 0.1% had SLE and their offspring had a higher frequency of congenital malformations (17.13% vs 11.99%, p<0.0001). After adjustment for age, parity, hypertension, diabetes, and fetal sex, the SLE group was found to be associated with an increased risk of congenital malformations in the nervous system (adjusted OR (aOR, 1.90; 95% CI, 1.20 to 3.03), eye, ear, face, and neck (aOR, 1.37; 95% CI, 1.09 to 1.71), circulatory system (aOR, 1.91; 95% CI, 1.67 to 2.20), and musculoskeletal system (aOR, 1.26; 95% CI, 1.05 to 1.52). Even after propensity matching, some of the tendencies were maintained. CONCLUSIONS: This nationwide population-based study in South Korea indicates that compared with the general population, neonates born to SLE mothers have a slightly increased risk of congenital malformations affecting the nervous system, head and neck, cardiovascular system, and musculoskeletal system. When a woman with lupus becomes pregnant, careful fetal ultrasound and newborn screening can be helpful in identifying the risk of potential malformations.

Risk of Bloodstream Infection in Patients with Systemic Lupus Erythematosus Exposed to Prolonged Medium-to-High-Dose Glucocorticoids.

OBJECTIVES: This study aimed to investigate the incidence rate and risk factors of bloodstream infection (BSI) in patients with systemic lupus erythematosus (SLE) exposed to medium to high doses of glucocorticoids. METHODS: This study included 1109 treatment episodes with prolonged (≥4 weeks) medium-to-high-dose glucocorticoids (≥15 mg/day prednisolone) in 612 patients with SLE for over 14 years. Clinical features regarding systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), immunosuppressant use, and laboratory results were obtained from the electronic medical database. The primary outcome of this study was the 1-year incidence of BSI. The effect of clinical factors on the outcome was investigated using a generalized estimating equation. RESULTS: During a total of 1078.64 person-years, 30 cases of BSI occurred, with an incidence rate of 2.78 (95% confidence interval (CI) 1.88-3.97) per 100 person-years. Mortality rate of the treatment episodes with BSI was 16.7%, which was significantly higher than that in the other episodes (incidence rate ratio (IRR) 19.59, 95% CI 7.33-52.44). When the incidence rate of BSI was stratified by baseline glucocorticoid dose and SLEDAI-2K score, a higher incidence rate of BSI occurred as disease activity or baseline glucocorticoid dose increased. In the multivariable analysis, SLEDAI-2K ≥20 (adjusted IRR (aIRR) 4.66, 95% CI 2.17-10.00), initial baseline prednisolone ≥ 60 mg/day (aIRR 2.42, 95% CI 1.11-5.32), and cumulative prednisolone dose ≥15 mg/day during the previous 6 months (aIRR 2.13, 95% CI 1.03-4.40) significantly increased the risk of BSI. CONCLUSION: In patients with SLE exposed to prolonged medium-to-high-dose glucocorticoids, the 1-year incidence rate of BSI was significantly higher than previously reported in the general patients with SLE. Severe disease activity, and high-dose glucocorticoid treatment previously or at baseline increased the risk of BSI.

Performance of cut-offs adjusted with positive control band intensity in line-blot assays for myositis-specific antibodies.

The diagnostic performance of band intensity (BI) cut-offs, adjusted by a positive control band (PCB) in a line-blot assay (LBA) for myositis-related autoantibodies (MRAs) is investigated. Sera from 153 idiopathic inflammatory myositis (IIM) patients with available immunoprecipitation assay (IPA) data and 79 healthy controls were tested using the EUROLINE panel. Strips were evaluated for BI using the EUROLineScan software, and the coefficient of variation (CV) was calculated. Sensitivity and specificity, area under the curve (AUC), and the Youden's index (YI) were estimated at non-adjusted or PCB-adjusted cut-off values. Kappa statistics were calculated for IPA and LBA. Although inter-assay CV for PCB BI was 3.9%, CV was 12.9% in all samples, and a significant correlation was found between BIs of PCB and seven MRAs (all P < 0.05). At adjusted BI (aBI) > 10, the negative conversion rate of myositis-specific autoantibody (MSA)-positivity at BI > 10 was 11.5% in controls and 1.3% in patients. The specificity, AUC, and YI for MSAs at aBI > 10 or > 20 were higher than those at non-adjusted cut-off values. Additionally, AUC (0.720), YI (0.440), and the prevalence of MRAs with kappa > 0.60 (58.3%) were the highest at aBI > 20. The overall sensitivity and specificity for MSAs were 50.3% and 93.7% at aBI > 20, respectively, and 59.5% and 65.8% with BI > 10, respectively. The diagnostic performance of LBA can be improved using PCB-adjusted BIs. aBI > 20 is the optimal cut-off for IIM diagnosis using the EUROLINE LBA panel.

Reliability and validity of PROMIS physical function, pain interference, and fatigue as patient reported outcome measures in adult idiopathic inflammatory myopathies: International study from the OMERACT myositis working group.

OBJECTIVE: Pain interference, fatigue, and impaired physical function are common features of idiopathic inflammatory myopathies (IIM). The objective of this study was to evaluate the construct validity and test-retest reliability of the Patient Reported Outcome Information System (PROMIS) Pain Interference 6av1.0, Fatigue 7av1.0, and Physical Function 8bv2.0 instruments. METHODS: Patient-Reported Outcome Measures (PROMs) were deployed to adult IIM patients from OMERACT Myositis Working Group (MWG) international clinic sites via two online surveys (2019, 2021). Internal consistency of each PROM was analyzed by Cronbach's α. Construct validity was determined by a priori hypotheses generated by the MWG with >75% agreement for each hypothesis and calculated with Pearson correlations. Test-retest reliability was assessed using intraclass correlation coefficient with PROMIS instruments administered at time zero and 7 days. RESULTS: Surveys were sent to 368 participants in total; participants who completed each questionnaire varied (n=65 to 263). For construct validity, 10 out of 13 a priori hypotheses were met supporting construct validity of PROMIS instruments (Pain Interference 3/4, fatigue 4/4, and Physical Function 3/5). Test-retest reliability was strong for all PROMIS instruments. All PROMIS instruments demonstrated excellent internal consistency. None of the measures demonstrated any ceiling or floor effects except for a ceiling effect in the Pain Interference instrument. CONCLUSIONS: This study presents test-retest reliability and construct validity evidence supporting PROMIS Pain Interference (6a v1.0), Fatigue (7a v1.0), and Physical Function (8b v2.0) using a large international cohort of patients with IIM. Internal consistency of these instruments was excellent. A ceiling effect was noted in the Pain Interference instrument.

Physician Perspectives on Vaccination in Patients With Autoimmune Inflammatory Rheumatic Diseases: An International Survey.

OBJECTIVE: To evaluate the perspective of physicians who care for patients with autoimmune inflammatory rheumatic disease (AIIRD) toward vaccination. METHODS: Physicians who care for patients with AIIRD were invited to participate in an online survey regarding their vaccination perspectives in adult patients with AIIRD. RESULTS: Survey responses of 370 physicians from Asia (41.1%), North America (41.6%), Europe (13.8%), and other countries (3.5%) were analyzed. Participants stated that rheumatologists (58.2%) should be primarily responsible for vaccination coverage, followed by general internists (19.3%) and family medicine practitioners (12.8%). Additionally, 96.7% of participants considered vaccination very important (≥ 4/5 rating) for patients with AIIRD. Despite these sentiments, only one-third (37%) reported vaccinating the majority (≥ 60%) of their patients. CONCLUSION: Physicians who care for patients with AIIRD agree that vaccines are effective and safe in patients with AIIRD. Unfortunately, they often do not ensure that their patients are adequately vaccinated. Further studies are needed to investigate how to improve vaccination coverage for this high-risk patient population.

A Multicenter, Prospective, Randomized, Parallel-Group Trial on the Effects of Temporary Methotrexate Discontinuation for One Week Versus Two Weeks on Seasonal Influenza Vaccination in Patients With Rheumatoid Arthritis.

OBJECTIVE: This clinical trial was conducted to investigate whether discontinuing methotrexate (MTX) for 1 week after seasonal influenza vaccination is noninferior to discontinuing for 2 weeks after vaccination in patients with rheumatoid arthritis (RA). METHODS: In this multicenter, prospective, randomized, parallel-group noninferiority trial, RA patients receiving a stable dose of MTX were randomly assigned at a ratio of 1:1 to discontinue MTX for 1 week or for 2 weeks after they received the quadrivalent 2021-2022 seasonal influenza vaccine containing H1N1, H3N2, B/Yamagata, and B/Victoria strains. The primary outcome measure was the proportion of patients with a satisfactory vaccine response, which was defined as ≥4-fold increase in antibody titers, as determined with the hemagglutination inhibition assay, against ≥2 of the 4 vaccine strains at 4 weeks after vaccination. RESULTS: The modified intent-to-treat population included 90 patients in the 1-week MTX hold group and 88 patients in the 2-week MTX hold group. The mean ± SD MTX doses were 12.6 ± 3.4 mg/week in the 1-week MTX hold group and 12.9 ± 3.3 mg/week in the 2-week MTX hold group. The proportion of satisfactory vaccine responses did not differ between the groups (68.9% versus 75.0%; P = 0.364). The rate of seroprotection and the fold increase in antibody titers for each of the 4 influenza antigens were similar between the groups. CONCLUSION: A temporary discontinuation of MTX for 1 week after vaccination was noninferior to a discontinuation of MTX for 2 weeks after vaccination, regarding induction of a satisfactory vaccine response to a seasonal influenza vaccine in patients with RA receiving a stable dose of MTX.