Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry

Introduction: To compare the efficacy of abatacept and tumor necrosis factor inhibitor (TNFi) in patients with anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and identify those who benefit most from abatacept over TNFi. Methods: This observational study identified RA patients who were ACPA-positive and initiated abatacept or TNFi from the Korean College of Rheumatology Biologics and Targeted therapy registry. Propensity score (PS) matching was performed to balance baseline confounding in abatacept- or TNFi-treated patients. The major endpoints were changes in Clinical Disease Activity Index (CDAI) and achievement of CDAI remission/low disease activity after 1 year of treatment. Subgroup analysis was mainly performed stratified by prior biologics use. Results: A total of 291 PS-matched, ACPA-positive RA patients who initiated abatacept (n = 97) and TNFi (n = 194) were included. From baseline CDAI scores of 26.52 in the abatacept group and 26.38 in the TNFi group, the mean changes after 1 year were - 16.78 and - 13.61, respectively (difference - 3.17, p = 0.020). The proportion of patients achieving CDAI remission/low disease activity was 68.0% with abatacept and 52.6% with TNFi (p = 0.013). In the subgroup analysis, patients that were biologics-naïve had better improvement in CDAI after treatment with abatacept than TNFi (difference - 3.35, p = 0.021). Conclusions: This real-world study suggests that abatacept may have better clinical response compared to TNFi in patients with established ACPA-positive RA, especially in those that were biologics-naïve.ope

Clinical analysis of gouty patients with normouricaemia at diagnosis

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Multivariable index for assessing the activity and predicting all-cause mortality in antineutrophil cytoplasmic antibody-associated vasculitis

BACKGROUND: So far, there has been no tool to estimate activity at diagnosis and predict all-cause mortality in patients with ANCA-associated vasculitis (AAV). Hence, we determined the initial predictors of them in patients with AAV. METHODS: We retrospectively reviewed the medical records of 182 patients with AAV. Severe AAV was defined as Birmingham Vasculitis Activity Score (BVAS) ≥ 16. The cutoffs were extrapolated by the receiver operator characteristic (ROC) curve. The odds ratio (OR) and the relative risk (RR) were assessed using the multivariable logistic regression analysis and the chi-square test, respectively. RESULTS: In the comparison analysis, patients with severe AAV exhibited the higher neutrophil and platelet counts, creatinine, erythrocyte sedimentation rate and C-reactive protein, and the lower lymphocyte count, hemoglobin, and serum albumin than those without. In the multivariable logistic regression analysis, creatinine ≥ 0.9 mg/dL (OR 2.264), lymphocyte count ≤ 1430.0/mm3 (OR 1.856), and hemoglobin ≤ 10.8 g/dL (OR 2.085) were associated with severe AAV. We developed a new equation of a multivariable index for AAV (MVIA) = 0.6 × (Lymphocyte count ≤ 1430.0/mm3 ) + 0.7 × (Hemoglobin ≤ 10.8 g/dL) + 0.8 × (Creatinine ≥ 0.9 mg/dL). The optimal cutoff of MVIA for severe AAV was set as 1.35. Severe AAV was identified more frequently in patients with MVIA at diagnosis ≥1.35 than those without (RR 4.432). Patients with MVIA at diagnosis ≥1.35 exhibited the lower cumulative patient survival rate than those without. CONCLUSION: Multivariable index for AAV could assess the cross-sectional activity and predict all-cause mortality in patients with AAV.ope

Clinical Significance of Anti-HSP 70 Antibody in the Patients with Systemic Lupus Erythematosus

Background :Heat shock proteins (HSPs), or stress proteins, are immunodominant antigens of many microorganisms. In this study, we have detected the anti-HSP 70 antibody and tried to explain the role of the antibody with respect to the pathogenesis of SLE. Furthermore, we have attempted to find out the possibility to link the presence of the autoantibody with the monitoring and diagnosis of systemic lupus erythematosus (SLE). Method :A total of 80 samples from 55 SLE patients were screened for the presence of anti-HSP 70 antibodies. Simultaneously 59 healthy people were tested as a control group. The anti-HSP 70 antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and confirmed by western blot in anti-HSP 70 antibody ELISA positive samples. The activity of disease state was confirmed by the patients’medical record and systemic lupus activity measure (SLAM). Result :The mean optical density (O.D.450) of ELISA in healthy controls and SLE patients were 0.15±0.18 (mean±S.D.) and 0.13±0.14. The correlation of SLAM Score and ELISA O.D. was r2 = 0.19, P = 0.014. And, the mean O.D. value of ELISA was 0.18±0.02 and 0.11±0.01 before and after treatment (P < 0.05). We compared samples with SLAM Score. The O.D. of anti-HSP 70 ELISA in these patients were 0.20±0.02 and 0.08±0.002 before and after treatment respectively (n=10, mean±S.D., P < 0.01). Conclusion :Anti-HSP 70 antibody was not a clinically useful diagnostic marker in SLE patients. However, the titer of anti-HSP 70 antibody can be used for the monitoring of the therapeutic effectiveness in these patients.ope

Autologous Haematopoietic Stem Cell Transplantation for Refractory Rheumatic Diseases

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Comparison of the efficacy and safety profiles of a pelubiprofen versus celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, phase III, non-inferiority clinical trial

BACKGROUND: Pelubiprofen is a prodrug of 2-arylpropionic acid with relatively selective effects on cyclooxygenase-2 activity. The aim of this study was to compare the efficacy and safety profiles of pelubiprofen with those of celecoxib in patients with rheumatoid arthritis. METHODS: This was a 6-week, multicenter, randomized, double-blind, double-dummy, parallel-group, phase III, non-inferiority clinical trial. The primary end point was non-inferiority of pain decrease from baseline to week-6 as determined using a 100 mm pain visual analog scale (VAS). Pelubiprofen was considered non-inferior to celecoxib if the lower limit of the 97.5% confidence interval for treatment difference [(pain reduction in pelubiprofen group) - (pain reduction in celecoxib group)] was more than -10 mm. The secondary end points were as follows: non-inferiority of (1) reduction of Korean health assessment questionnaire (KHAQ) score; (2) decreased duration of morning stiffness; and (3) decrease in the frequency and total dose of rescue drugs after 6 weeks of treatment. RESULTS: Seventy-seven patients in the pelubiprofen group and 68 patients in the celecoxib group started the study medication. Pelubiprofen was non-inferior to celecoxib with regard to reduction in VAS pain severity (difference, mean ± SD 5.0 ± 20.1; 97.5% CI, -2.3 to ∞). Pelubiprofen was also non-inferior to celecoxib in terms of the secondary end points, such as, decrease in KHAQ score (0.0 ± 0.5, 97.5% CI -0.2 to ∞), decrease in duration of morning stiffness (median 0.0 minute in both groups), and decrease in the frequency (0.7 ± 3.5, 97.5% CI -0.6 to ∞) and total amount (0.7 ± 3.6, 97.5% CI -0.6 to ∞) of rescue medication uses during the 6 week study period. Safety analysis revealed 31.2% patients in the pelubiprofen group and 20.6% patients in the celecoxib group experienced an adverse drug reaction (ADR). The frequency of gastrointestinal ADRs was 20.8 % and 8.8%, respectively. CONCLUSIONS: Pelubiprofen was found to be as effective as celecoxib at pain reduction and for relieving stiffness in RA patients. However, more patients in the pelubiprofen group experienced ADR and the frequency of gastrointestinal ADRs was higher in the pelubiprofen group. ClinialTrials.gov identifier: NCT01781702.ope

Controlling Nutritional Status Score is Associated with All-Cause Mortality in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

PURPOSE: The controlling nutritional status (CONUT) score was developed to detect undernutrition in patients. Here, we investigated whether the CONUT score estimated at diagnosis could help predict poor outcomes [all-cause mortality, relapse, and end-stage renal disease (ESRD)] of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We retrospectively reviewed and collated data, including baseline characteristics, clinical manifestations (to calculate AAV-specific indices), and laboratory results, from 196 newly diagnosed AAV patients. Serum albumin, peripheral lymphocyte, and total cholesterol levels (at diagnosis) were used to calculate CONUT scores. RESULTS: In total, 111 patients had high CONUT scores (≥3), which showed higher frequency of myeloperoxidase-ANCA and ANCA positivity, and demonstrated higher AAV-specific indices. The optimal cut-offs of CONUT score (at diagnosis) for predicting all-cause mortality and ESRD were ≥3.5 and ≥2.5, respectively. Patients with CONUT scores higher than the cut-off at diagnosis exhibited lower cumulative and ESRD-free survival rates compared to those with lower scores than the cut-off. In multivariable analyses, diabetes mellitus [hazard ratio (HR): 4.394], five-factor score (HR: 3.051), and CONUT score ≥3.5 (HR: 4.307) at diagnosis were independent predictors of all-cause mortality, while only serum creatinine (HR: 1.714) was an independent predictor of ESRD occurrence.ope

Rituximab Biosimilar Prevents Poor Outcomes of Microscopic Polyangiitis and Granulomatosis with Polyangiitis as Effectively as Rituximab Originator

Purpose: There has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®. Materials and methods: We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®. Results: The median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®. Conclusion: Truxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.ope

Multicenter Study in Efficacy and Safety of Celecoxib in Patients with Rheumatoid Arthritis and Osteoarthritis

Objective: The aim of this study was to define the efficacy and safety of celecoxib in Korean patients with rheumatoid arthritis and osteoarthritis. In addition, the impact of gastrointestinal symptom severity on health related quality of life (HRQoL) was measured before and after the treatment with celecoxib. Methods: Three hundred seventy nine patients with rheumatoid arthritis (n=175) and osteoarthritis (n=204) were enrolled from 25 centers from May 2004 to December 2004. After treatment of celecoxib for 4 weeks, efficacy was determined by physician`s global assessment and EQ-5D. Severity of gastrointestinal (GI) symptom was assessed by visual analogue scale. Results: Treatment made improvement in 263 patients (69.4%), but 108 patients (28.5%) didn`t show change in their symptom and 8 patients (2.1%) were aggravated after treatment. Mean change was 0.129±0.3 in EQ-5D utility score (p＜0.05), 11.8±17.8 in VAS in EQ-5D (p＜0.05) and -7.9±19.6 in GI symptom severity (p＜0.05). Blood pressure was not elevated after treatment and there was no cardiovascular adverse event. Gastrointestinal symptom improvement correlates with improvement in VAS (r=0.2, p＜0.01). Conclusion: Celecoxib is not only effective in patients with rheumatoid arthritis and osteoarthritis but also helpful in reducing GI symptom.ope

Two-year clinical outcomes after discontinuation of long-term golimumab therapy in Korean patients with rheumatoid arthritis

Background/aims: The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods: Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results: The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusion: Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.ope