Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

ObjectiveRheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations.MethodsAssociation analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls.ResultsIn unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16–1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19–1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65–0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected.ConclusionThe independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified

Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope

INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. METHODS: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA

Efficacy and safety of abatacept in patients with rheumatoid arthritis with previous malignancy

Background: Abatacept (ABT) is known to lower infection risk than other biologics and is effective and safe in elderly patients with rheumatoid arthritis (RA). However, there were inconsistent reports on the impact of ABT on malignancies which are more common in the elderly and strongly related to prognosis. Objectives: This study aimed to evaluate the efficacy and safety of ABT in patients with RA with previous malignancy in clinical practice. Design: A multicenter, retrospective study. Methods: Patients who received ABT for RA in two hospitals in Yokohama until May 2022 were included in this study. The patients were divided into two groups according to the presence or absence of a history of malignancy (no previous malignancy: NP group, previous malignancy: PM group). The collected parameters were compared between the groups using propensity score matching. Results: In this study, 312 patients were included, of whom 73 had previous malignancies when starting ABT. The age at ABT initiation was significantly higher in the PM group, the rate of methotrexate use was significantly lower in the PM group, and the Steinbrocker stage was significantly higher in the PM group. After matching these 3 factors, 68 patients were selected from each group. No significant differences in the ABT continuation rate, and malignancy incidence were observed between the two groups after ABT initiation. In addition to these factors, when matched for smoking history, interstitial lung disease, disease duration, sex, and inflammatory status, which are known risk factors for malignancy in RA, 40 patients were selected from each group. No significant differences in the ABT continuation rate, and malignancy incidence were observed between the two groups after ABT initiation. Conclusion: In our clinical practice, ABT was as effective and safe in patients with a history of malignancy as in those without

Prognostic factors in interstitial lung disease associated with primary Sjögren's syndrome: a retrospective analysis of 33 pathologically-proven cases.

INTRODUCTION: Interstitial lung disease associated with primary Sjögren's syndrome (pSS-ILD) shows several patterns such as nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Although UIP is a well-recognized prognostic determinant in idiopathic interstitial pneumonias, whether this is also the case in pSS-ILD is unclear. The objectives of this study were to evaluate the prognostic effect of UIP, and to identify the prognostic factors in pSS-ILD. METHODS: A retrospective review of medical records identified 33 consecutive patients with pathologically-proven pSS-ILD. Each patient was classified into each ILD pattern by multidisciplinary analysis. Baseline clinical-radiologic-pathologic characteristics and survival rates were compared between the ILD patterns. Finally, the prognostic factors in pSS-ILD were assessed by univariate and subsequent multivariate analyses using Cox's proportional hazards regression model. RESULTS: pSS-ILD patients were diagnosed with NSIP (n = 22) or UIP (n = 11). The median follow-up period was 110 months, and five-year survival rate was 87.3% in the total patient population. The prognosis of the UIP patients was not significantly different from that of the NSIP patients (NSIP to UIP, hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.18-3.36, P = 0.73). Multivariate analysis identified PaCO2 (HR: 1.68 per 1 Torr increase, 95% CI: 1.24-2.28, P < 0.01), extent of reticular abnormality on high-resolution CT (HR: 4.17 per 1-grade increment, 95% CI: 1.18-14.73, P = 0.03), and severity of fibroblastic foci (HR: 9.26 per 1-grade increment, 95% CI: 1.74-49.35, P < 0.01) as prognostic factors in pSS-ILD. CONCLUSIONS: UIP in pSS-ILD was not related to poorer prognosis than NSIP. Assessment of detailed clinical-radiologic-pathologic findings is more important than distinguishing UIP to evaluate prognosis in this disease

Kaplan–Meier survival curves for patients with interstitial lung disease associated with primary Sjögren’s syndrome.

<p>(a) Survival curve for the total patient population. Five-year survival rate was 87.3%. (b) Comparison of survival curves between the NSIP (n = 22) and UIP (n = 11) patients. Open circles or open squares show censored cases in NSIP group or UIP group, respectively. The prognosis between the two groups was not significantly different (<i>P</i> = 0.93 in log–rank test). UIP: usual interstitial pneumonia; NSIP: nonspecific interstitial pneumonia.</p

Examples of pathological scoring (hematoxylin–eosin, × 100).

<p>Typical images in each grade of fibroblastic foci (straight arrows) [(a): grade 1 and (b): grade 3] and bronchiolar fibrosis [(c): grade 1 and (d): grade 3] were listed.</p

Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients.

INTRODUCTION: Autoantibodies to ribonucleoprotein are associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA). Many studies on associations between human leukocyte antigen (HLA) alleles and RA have been reported, but few have been validated in RA subpopulations with anti-La/SS-B or anti-Ro/SS-A antibodies. Here, we investigated associations of HLA class II alleles with the presence of anti-Ro/SS-A or anti-La/SS-B antibodies in RA. METHODS: An association study was conducted for HLA-DRB1, DQB1, and DPB1 in Japanese RA and systemic lupus erythematosus (SLE) patients that were positive or negative for anti-Ro/SS-A and/or anti-La/SS-B antibodies. RESULTS: An increased prevalence of certain class II alleles was associated with the presence of anti-Ro/SS-A antibodies as follows: DRB1*08:03 (Pc = 3.79×10(-5), odds ratio [OR] 3.06, 95% confidence interval [CI] 1.98-4.73), DQB1*06:01 (Pc = 0.0106, OR 1.70, 95%CI 1.26-2.31), and DPB1*05:01 (Pc = 0.0040, OR 1.55, 95%CI 1.23-1.96). On the other hand, DRB1*15:01 (Pc = 0.0470, OR 3.14, 95%CI 1.63-6.05), DQB1*06:02 (Pc = 0.0252, OR 3.14, 95%CI 1.63-6.05), and DPB1*05:01 (Pc = 0.0069, OR 2.27, 95% CI 1.44-3.57) were associated with anti-La/SS-B antibodies. The DPB1*05:01 allele was associated with anti-Ro/SS-A (Pc = 0.0408, OR 1.69, 95% CI 1.19-2.41) and anti-La/SS-B antibodies (Pc = 2.48×10(-5), OR 3.31, 95%CI 2.02-5.43) in SLE patients. CONCLUSION: HLA-DPB1*05:01 was the only allele associated with the presence of both anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese RA and SLE patients

Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial. Modern Rheumatology 20:531–538 DOI

Abstract The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTXnaïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E ? M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E ? M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E ? M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E ? M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX

Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial

Objectives The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor alpha (TNF-alpha)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods In this multicentre randomised trial, patients with IFX-naive rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-alpha until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) <= 3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI <= 3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment