Uncovering risk factors for adverse events and infections in rheumatoid arthritis and rheumatoid arthritis with interstitial lung disease under treatment with biologics or targeted synthetic DMARDs: insights from the KOBIO Registry.

OBJECTIVES: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry. METHODS: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD. RESULTS: Among all patients with RA, 45.7% withdrew b/tsDMARDs, whereas among those with RA-ILD, a higher proportion of 57.4% withdrew their treatment regimen. The main reason for withdrawing b/tsDMARDs in the RA-ILD group was AEs, with infections accounting for the largest proportion of reported AEs. In multivariable analysis of the risk factors for overall AEs and infections in the RA-ILD group, older age was identified as a risk factor for overall AEs (odds ratio [OR], 3.01; p=0.014), and only a current smoking status was identified as a risk factor for infections (OR, 2.11; p=0.035). CONCLUSIONS: Patients with RA-ILD exhibited a higher rate of b/tsDMARDs withdrawal due to overall AEs and infections than those with RA without ILD. In the RA-ILD group, older age was identified as a risk factor for overall AEs, whereas a current smoking status was identified as a risk factor for infections.

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.

Corrigendum: Korean treatment recommendations for patients with axial spondyloarthritis.

[This corrects the article on p. 151 in vol. 30, PMID: 37476674.].

The Risk of COVID-19 and Its Outcomes in Korean Patients With Gout: A Multicenter, Retrospective, Observational Study.

This retrospective cohort study aimed to compare coronavirus disease 2019 (COVID-19)-related clinical outcomes between patients with and without gout. Electronic health record-based data from two centers (Seoul National University Hospital [SNUH] and Boramae Medical Center [BMC]), from January 2021 to April 2022, were mapped to a common data model. Patients with and without gout were matched using a large-scale propensity-score algorithm based on population-level estimation methods. At the SNUH, the risk for COVID-19 diagnosis was not significantly different between patients with and without gout (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.59-1.84). Within 30 days after COVID-19 diagnosis, no significant difference was observed in terms of hospitalization (HR, 0.57; 95% CI, 0.03-3.90), severe outcomes (HR, 2.90; 95% CI, 0.54-13.71), or mortality (HR, 1.35; 95% CI, 0.06-16.24). Similar results were obtained from the BMC database, suggesting that gout does not increase the risk for COVID-19 diagnosis or severe outcomes.

Knee osteoarthritis with a high grade of Kellgren-Lawrence score is associated with a worse frailty status, KNHANES 2010-2013.

Frailty as a syndrome of physical decline in late life is associated with adverse health outcomes. Knee osteoarthritis (KOA) could contribute to frailty conditions. The objective of this study was to evaluate the impact of KOA on frailty risk in a Korean National Health and Nutrition Examination Survey (KNHANES) cohort. In this study (N, total = 11,910, age; 64.10 years old [63.94-64.27; mean 95% CI], sex (female, %); 6,752 (56.69)), KOA patients were defined as those with knee joint pain and grade 2 Kellgren-Lawrence (K-L) or more on plain radiographic images who were 40 years old or older in Korean population data of KNHANES. The frailty index was calculated using 46 items related to co-morbidities and laboratory parameters. The impact of KOA on frailty risk was evaluated with logistic regression analyses. The prevalence of KOA patients was 35.6% [95% CI 34.7-36.46]. In polytomous logistic regression, the relative risk ratio (RRR) of KOA was significantly increased in the pre-frail group (2.76, 95% CI 2.30-3.31) and the frail group (7.28, 95% CI 5.90-8.98). RRR of frailty was significantly increased in patients with K-L grade 3 (1.36, 95% CI 1.13-1.63) and K-L grade 4 (2.19, 95% CI 1.72-2.79). Older age, higher BMI, smoking status, alcohol intake, low-income status, higher WBC count, higher platelet count, higher serum creatinine level and low estimated GFR were significantly associated with increased frailty risk. High hemoglobin and regular walking habits were associated with decreased frailty risk in KOA patients. In this large observation population- based survey cohort, KOA is linked to an increased risk of frailty syndrome. We found a significant connection between KOA and frailty syndrome. These results show that we need to think about the overall health of people with KOA and give them special care to prevent frailty syndrome.

Factors for achieving target serum uric acid levels after initiating urate-lowering therapy in patients with gout: results from the ULTRA registry.

Achieving target serum uric acid (SUA) levels is important in gout management. Guidelines recommend lowering SUA levels to < 6 mg/dL; however, many patients fail to reach this target, even with uric acid-lowering therapy (ULT). This study investigated clinical characteristics of target SUA achievers among Korean patients with gout. This study used data from the ULTRA registry, a nationwide inception cohort established in September 2021 that enrolls patients with gout who initiate ULT. Demographic, clinical, and laboratory data were collected at baseline; the 6-month follow-up. Patients were divided into two groups: target achievers (SUA level < 6 mg/dL at 6 months) and non-achievers. The mean participant (N = 117) age was 56.1 years, and 88.0% were male. At 6 months, 83 patients (70.9%) reached target SUA levels. Target achievers had better drug adherence (≥ 80%) to ULT (97.6% vs. 76.5%; p < 0.01) than non-achievers. Target non-achievers had a higher percentage of a family history of gout (32.4% vs. 10.8%; p < 0.01) and less antihypertensive agent use (38.2% vs. 59.0%; p = 0.03) than target achievers. Multivariate regression analysis revealed that good adherence to ULT, the absence of a family history of gout, and antihypertensive agent use were key factors associated with achieving target SUA levels at 6 months.

The predictability of ASDAS on drug survival in patients with ankylosing spondylitis on biologic therapy: data from the KOBIO registry.

Background: The Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) is largely used for assessing disease activity in patients with AS. Objectives: We aimed to investigate the predictability of ASDAS on drug survival in patients with low Bath AS Disease Activity Index (BASDAI) during biologic therapy. Design: Using data from multi-center, prospective, observational prospective cohort, Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry. Methods: The study population consisted of patients enrolled in the KOBIO registry from December 2012 to December 2018. The baseline demographic data and variables such as extra-articular manifestations, HLA-B27 positivity, family history of spondyloarthritis, ASDAS C-reactive protein (CRP), BASDAI, and Bath AS Functional Index scores were collected from the database. The disease activity indices were followed yearly after initiating a tumor necrosis factor (TNF) inhibitor (TNFi). Disease activities were defined as high (ASDAS-CRP ⩾ 2.1, BASDAI ⩾ 4) and low (ASDAS-CRP < 2.1, BASDAI < 4). Results: Data from 1773 patients were analyzed. Among 269 patients with low BASDAI at baseline, 151 (56.1%) patients had high ASDAS-CRP, yet in 142 patients with low ASDAS-CRP at baseline, only 24 (16.9%) patients had a high BASDAI. High ASDAS-CRP captured more patients who had initiated or switched to a TNFi than those with high BASDAI (92.5% versus 84.8%, respectively, p < 0.001). Moreover, among AS patients with low BASDAI after 1 year of therapy, drug persistence in the following year was significantly lower in patients with high ASDAS than in those with low ASDAS (68.7% versus 82.5%, p < 0.001). Conclusion: ASDAS-CRP not only has its advantages over BASDAI in assessing disease activity but also low ASDAS-CRP at 1 year can be a marker of long-term drug survival of TNFi therapy.

Reliability and Validity of the Korean Version of the Gout Impact Scale.

BACKGROUND: The Gout Impact Scale (GIS), part of the Gout Assessment Questionnaire 2.0, measures gout-specific health-related quality of life (HRQOL). This study aimed to translate the GIS into Korean and validate the Korean version (K-GIS) using generic HRQOL measures. METHODS: The GIS was translated into Korean and back-translated into English. We asked patients aged 18 years or older who met the 2015 gout classification criteria to fill out the questionnaires (from January 2022 to June 2022); the K-GIS (5 scales [0-100 scores each]), along with the Korean version of Health Assessment Questionnaire (HAQ) and EuroQol-5 dimension (EQ-5D). We investigated the internal consistency, construct validity, and discriminative validity for gout characteristics of K-GIS. The K-GIS form was administrated to patients 4 weeks later to assess the test-retest reliability using the intraclass correlation coefficient (ICC). RESULTS: One hundred patients completed the questionnaire. The mean ± standard deviation age of the patients was 53.0 ± 15.1 years, and 99.0% of the patients were men. All scales had high degree of internal consistency (Cronbach's α = 0.59 to 0.96) and test-retest reliability (n = 18, ICC = 0.83 to 0.94, all P < 0.001), except for unmet gout treatment needs. Weak-to-moderate correlations were observed between the K-GIS scales and HAQ or EQ-5D (r = 0.21 to 0.46). The K-GIS scores were significantly higher in the presence of bone erosion, absence of urate-lowering therapy, serum urate levels > 6 mg/dL, frequent gout flares in the past year, and fewer comorbidities. In contrast, neither the HAQ nor the EQ-5D could discern these subsets of patients. CONCLUSION: The K-GIS is a reliable and valid HRQOL measure for patients with gout. Higher K-GIS scores were associated with clinical characteristics leading to unfavorable outcomes, which were not demonstrated by the HAQ and EQ-5D.

Unveiling difficult-to-treat rheumatoid arthritis: long-term impact of biologic or targeted synthetic DMARDs from the KOBIO registry.

BACKGROUND: While the availability of biological or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) has improved outcomes for rheumatoid arthritis (RA) patients, there remains a subset of individuals who fail to achieve low disease activity or remission despite multiple cycles of b/tsDMARDs. This state is referred to as 'difficult-to-treat (D2T)' RA. METHODS: Data from the Korean College of Rheumatology Biologics registry were utilized to analyze patients with RA who were treated with b/tsDMARDs. RESULTS: Among 2,321 RA patients with RA treated with b/tsDMARDs, 271 (11.7%) were diagnosed with D2T RA. Lower age (OR = 0.98, p < 0.001), longer disease duration (OR = 1.06, p < 0.001), lower patient global assessment (OR = 0.89, p = 0.045), higher SDAI (OR = 1.06, p = 0.014) and RAPID3 (OR = 1.06, p = 0.002), lower RF positivity (OR = 0.65, p = 0.04), and lower prior use of methotrexate (OR = 0.44, p = 0.008), sulfasalazine (OR = 0.59, p = 0.003), and leflunomide (OR = 0.67, p = 0.013) were associated with D2T RA. The drug survival rate of b/tsDMARDs did not differ between patients with D2T RA and non-D2T RA (p = 0.35). However, the drug survival of individual b/tsDMARD differed between patients with D2T RA and non-D2T RA after eight years. Patients with D2T RA withdrew from b/tsDMARDs due to inefficacy more frequently than those without D2T RA (p < 0.001). CONCLUSIONS: D2T RA patients experienced higher disease activity despite maintaining b/tsDMARD therapy. Withdrawal rates due to inefficacy were higher in D2T RA. Effective therapeutic strategies are needed to improve disease control and treatment outcomes in this unique patient population.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5-12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13-16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Treatment Sequence After Initiating Biologic Therapy for Patients With Rheumatoid Arthritis in Korea: A Nationwide Retrospective Cohort Study.

Objective: To evaluate treatment patterns and healthcare resource utilization (HCRU) after initiating biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with rheumatoid arthritis (RA). Methods: Patients newly diagnosed with RA in 2014 were identified and followed up on using the Korean National Health Insurance Database until 2018. The initial line of therapy (LOT) or LOT1 included patients treated with conventional DMARDs (cDMARD). Patients who started a bDMARD were assigned to LOT2 bDMARD. Those who moved from a bDMARD to a Janus kinase inhibitor were assigned to LOT3. Analyzed outcomes were treatment patterns and HCRU in LOT2 bDMARD. Results: The most prescribed initial bDMARD was a tumor necrosis factor inhibitor. Seventy-five percent of patients had changes in treatment after starting a bDMARD, such as addition/removal or switch of a DMARD, and transition to LOT3. For the first and second changes in LOT2 bDMARD, adding a cDMARD to a bDMARD was more common than switching to another bDMARD (7.98% vs. 2.93% for the first change, and 17.10% vs. 6.51% for the second change). Tocilizumab was the most common bDMARD that was switched to. Forty-eight percent of patients had at least one hospitalization after initiating bDMARDs. Of these patients, 64.3% were admitted due to RA-related reasons. Conclusion: This real-world study provides information on treatment characteristics of RA patients in Korea after starting a bDMARD. In contrary to guidelines, cDMARD addition was more often than bDMARD switches in daily clinical practice.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Low-dose RaDiation therapy for patients with KNee osteoArthritis (LoRD-KNeA): a protocol for a sham-controlled randomised trial.

INTRODUCTION: Low-dose radiation therapy (LDRT) for osteoarthritis (OA) has been performed for several decades. However, supporting evidence from randomised studies using modern methodologies is lacking, and a recently published randomised study failed to show the significant benefit of LDRT. The presented trial aims to evaluate the efficacy and safety of LDRT for patients with knee OA. METHODS AND ANALYSIS: This prospective, multicentre, randomised trial will be conducted in the Republic of Korea. A total of 114 participants will be randomly assigned (1:1:1) to receive sham irradiation, 0.3 Gy/6 fractions of LDRT or 3 Gy/6 fractions of LDRT. Key inclusion criteria are primary knee OA with Kellgren-Lawrence grade 2-3 and visual analogue scale 50-90 when walking at the baseline. The primary endpoint is the rate of responders at 4 months after LDRT according to the OARSI-OMERACT criteria. Concomitant use of analgesics is prohibited until the primary efficacy evaluation is scheduled. ETHICS AND DISSEMINATION: Currently, approval from the Ministry of Food and Drug Safety of the Republic of Korea and the institutional review board of each participating hospital has been obtained. Patient enrolment began in October 2022 and is ongoing at three participating sites. The results will be disseminated to academic audiences and the public via publication in an international peer-reviewed journal and presentation at conferences. This trial will provide valuable information on the safety and efficacy of LDRT for patients with knee OA. TRIAL REGISTRATION NUMBER: NCT05562271.

Retention Rate and Safety of Biologic and Targeted Synthetic DMARDs in Patients with RA-Associated Interstitial Lung Disease: A KOBIO Registry Study.

OBJECTIVES: This study aimed to evaluate the long-term retention and safety of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) and identify the factors associated with drug withdrawal in patients with rheumatoid arthritis (RA) with interstitial lung disease (ILD) enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry. METHODS: We investigated adults with RA (n = 2266) administered with bDMARDs or tsDMARDs between 2012 and 2021. Propensity score matching (1:3) was performed between patients with RA with ILD (RA-ILD) and without ILD (RA-no ILD). The Kaplan-Meier method was used to analyse drug survival and a logistic regression model to identify withdrawal-related factors in RA-ILD. RESULTS: One hundred and fifty-nine patients with RA-ILD were matched with 477 patients with RA-no ILD. The 5-year drug retention rate was lower in RA-ILD than in RA-no ILD (log-rank p = 0.020), and both the ILD and no-ILD groups had statistical differences of drug retention rate among agents (log-rank p = 0.019 and 0.020, respectively). In the RA-ILD group, Janus kinase inhibitors had the highest drug retention rate (64.3%), and tumour necrosis factor-α inhibitors showed the lowest retention rate (30.6%). Approximately 58.5% and 48.4% of the patients with RA-ILD and RA-no ILD, respectively, withdrew from their regimen, and the main cause of withdrawal in RA-ILD was adverse events, followed by inefficacy. In the logistic regression analysis, current smoking had a negative effect on drug retention (odds ratio [OR]: 9.938, 95% confidence interval [CI]: 2.550-38.733; p < 0.001), while concomitant corticosteroid use had a protective effect against withdrawal (OR: 0.284, 95% CI: 0.008-0.917; p = 0.035) in RA-ILD. CONCLUSION: The patients with RA-ILD had lower bDMARD and tsDMARD retention rates than those with RA-no ILD. In the RA-ILD group, current smoking and concomitant corticosteroid use were associated factors affecting drug withdrawal.

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.

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.