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Objective@#This study aims to evaluate the change in serum metalloproteinase-3 (MMP-3) following the management of active rheumatoid arthritis (RA) and define the relationships between MMP-3 and disease activity indices. @*Methods@#Data from a previously reported a 24-week, randomized controlled trial to investigate efficacy of tocilizumab in active RA refractory to methotrexate were analyzed. The serum level of MMP-3 were measured at week 0, 12, 20, and 24. The changes in MMP-3, and the relationship between MMP-3 and clinical parameters was assessed based on treatment group, methotrexate with or without tocilizumab. @*Results@#A total of 95 patients were included in this study. The serum MMP-3 significantly decreased and showed similar pattern with other disease activity indices during treatment period in both treatment groups (p0.05). @*Conclusion@#Serum MMP-3 showed positive correlation with disease activity indices in active RA patients. Furthermore, serum MMP-3 significantly decreased from baseline to week 20. As there is no single serum marker that can represent the disease activity particularly in tocilizumab treatment, MMP-3 might be a useful adjunct indicator to evaluate the treatment response in active RA patients.
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Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.
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The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.
ABSTRACT
Mixed cryoglobulinemic vasculitis (CV) is occasionally caused by autoimmune diseases including systemic sclerosis. Multiorgan involvement such as skin, kidney, and peripheral nerve involvement is common in mixed CV. However, central nervous system (CNS) involvement is extremely rare. Here, we report a case of overlap syndrome of limited cutaneous systemic sclerosis and mixed cryoglobulinemic vasculitis with CNS involvement. The neurologic deficits and systemic symptoms improved promptly after steroid and cyclophosphamide therapy.
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The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.
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The treatment of adult-onset Still's disease (AOSD) aims to control systemic inflammation and prevent organ damage. Systemic inflammation can be controlled with corticosteroid (CS) monotherapy in most cases. However, symptoms often flare as CS is tapered, often requiring long-term CS treatment, with its associated risks of infection, cardiovascular disease, and osteoporosis. Disease-modifying antirheumatic drugs (DMARDs) are often used as CS-sparing agents; however, the choice of DMARD has been largely empirical. Methotrexate (MTX) is recommended as the first-line steroid-sparing drug due to its well-known efficacy and safety in rheumatoid arthritis (RA). When MTX treatment is unsuccessful in AOSD, the choice of a second-line drug has not been established. In RA, leflunomide (LEF) has been used as an alternative to or in combination with MTX. To date, there has been no adequate assessment of the combination of LEF and MTX in AOSD. Here, we report a case of refractory chronic AOSD successfully treated with the MTX-LEF combination.
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Background@#Causes of weight change after tocilizumab treatment are unclear. We aimed to investigate the effects of tocilizumab treatment on body weight and serum adipokine levels in patients with rheumatoid arthritis (RA). @*Methods@#In this retrospective cohort study, we evaluated weight changes in patients with RA who received methotrexate (Cohort I) or tocilizumab with methotrexate (Cohorts II and III) for 24 weeks. Adipokine concentrations at baseline and 24 weeks were analyzed in Cohorts I and III. Cohorts I and II received tocilizumab therapy for an additional 48 weeks, during which weight changes were monitored (24–72 weeks). @*Results@#No significant weight change occurred after 24 weeks of methotrexate treatment (mean difference, −0.2 kg; P = 0.630), but was observed after 24 weeks of tocilizumab treatment (mean difference, +0.9 kg; P = 0.010). Weight changed regardless of the treatment response in both treatment groups. The leptin–adiponectin ratio (P = 0.015) and levels of adiponectin (P < 0.001), leptin (P < 0.001), and resistin (P = 0.003) increased significantly after 24 weeks of tocilizumab, but not methotrexate treatment. After 24, 48 and 72 weeks of tocilizumab treatment in Cohort II, mean (95% confidence interval [CI]) weight changes from baseline were +0.7 (0.0–1.4), +1.2 (0.4–2.0) and +1.1 (0.2–2.0) kg, respectively, and mean (95% CI) percent weight changes from baseline were +1.3% (0.1%–2.6%), +2.2% (0.7%–3.6%), and +2.0% (0.4%–3.7%) at 24, 48, and 72 weeks, respectively. @*Conclusion@#Weight and the leptin–adiponectin ratio increased after tocilizumab treatment. Given that cardiovascular (CV) risk factors may deteriorate in patients with RA who receive tocilizumab, further studies are required to determine the effects of weight gain on CV outcomes in these patients.
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Background@#The D-dimer test is a screening tool for venous thromboembolism (VTE);however, its utility for patients with systemic lupus erythematosus (SLE) remains unclear.Here, we examined the utility of the D-dimer test as a screening tool for VTE in SLE patients. @*Methods@#SLE patients (n = 276) and age- and sex-matched patients with non-rheumatic disease (n = 1,104), all of whom underwent D-dimer testing to screen for VTE, were enrolled.The sensitivity and specificity and receiver operating characteristics curve of the D-dimer test were compared in both groups. Then, subgroup of SLE patients in whom the D-dimer test can be useful was sought. @*Results@#The incidence of VTE was more common in SLE patients than controls (10.9% vs.4.0%). Although the sensitivity of the D-dimer test was comparable between SLE patients and controls (93.3% vs. 90.9%), the specificity of the test was profoundly lower in SLE patients compared to controls (28.4% vs. 84.4%). The area under the curve (AUC) of the D-dimer for VTE was 0.669 in SLE patients and 0.90 in control group. Multiple linear regression analysis demonstrated that SLE disease activity index-2000 (SLEDAI-2K) was significantly associated with D-dimer levels in SLE patients (β = 0.155; P = 0.022). Subgroup analysis showed that the AUC is moderate (0.768) with low disease activity, while it is low (0.518) with high SLEDAI-2K. @*Conclusion@#The D-dimer test may not be a useful screening tool for VTE in patients with active SLE. D-dimer test for predicting VTE in SLE patients should be differentially applied according to disease activity of SLE.
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Background/Aims@#Myelodysplastic syndrome (MDS) is caused by genetic and epigenetic alteration of hematopoietic precursors and immune dysregulation. Approximately 20% of patients with MDS develop an autoimmune disease (AID). Here, we investigated whether particular genetic mutations are associated with AID in patients with MDS. @*Methods@#Eighty-eight genetic mutations associated with myeloid malignancy were sequenced in 73 MDS patients. The association between these mutations and AID was then analyzed. @*Results@#The median age of the 73 MDS patients was 70 years (interquartile range, 56 to 75), and 49 (67.1%) were male. AID was observed in 16 of 73 patients (21.9%). Mutations were detected in 57 (78.1%) patients. The percentage (68.8% vs. 80.7%, p = 0.32) and the mean number of mutations (1.8 ± 1.6 vs. 2.2 ± 1.8, p = 0.34) in MDS patients with or without AID were similar. However, the ten-eleven translocation- 2 (TET2) mutation rate was significantly higher in patients with AID than in those without (31.3% vs. 5.3%, respectively; p = 0.001). All TET2 mutations were variants of strong clinical significance. @*Conclusions@#Mutation of TET2 in patients with MDS may be associated with increased risk of developing AID.
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BACKGROUND/AIMS@#To investigate the efficacy and safety of tocilizumab (TCZ) humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients with active rheumatoid arthritis (RA) refractory to conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX)@*METHODS@#The main study was a 24-week, randomized, double-blind, controlled trial that was followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo was intravenously administered every 4 weeks.@*RESULTS@#Those treated with TCZ showed more favorable outcomes in terms of 20% according to the American College of Rheumatology response criteria (ACR20) and ACR50 responses, individual parameters of ACR core set, disease activity score in 28 joints (DAS28) remission, and European League Against Rheumatism (EULAR) response at week 24. These improvements were maintained or increased during the extension period. DAS28 remission at week 72 was associated with EULAR good response at week 12. The patients who experienced any adverse event (AE) were more frequent in the TCZ group compared to the placebo group. Most AEs were mild or moderate in intensity, although TCZ therapy had possible AEs including serious infection, abnormal liver function, and atherogenic lipid profile.@*CONCLUSIONS@#TCZ infusion add-on is highly efficacious and well-tolerated in Korean patients with active RA refractory to conventional DMARDs including MTX. EULAR good response at week 12 could predict DAS28 remission at week 72.
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BACKGROUND/AIMS@#To analyze clinical characteristics of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA), especially in patients with poor prognosis.@*METHODS@#Seventy-seven RA patients with ILD and 231 age, sex, and disease duration-matched RA patients without ILD were enrolled in this retrospective study. Epidemiologic, clinical, and laboratory information were obtained through a medical chart review. Logistic regression analysis was used to estimate the risk of mortality in RA patients with ILD.@*RESULTS@#Compared to the RA without ILD group, the RA with ILD group had significantly higher titers of rheumatoid factor and the anti-cyclic citrullinated peptide (p = 0.001 for both), higher levels of C-reactive protein (CRP) at the time of RA diagnosis (p = 0.014), and a higher erythrocyte sedimentation rate (p = 0.022) and CRP levels (p < 0.001) throughout the 10-year follow-up period. These patients also received a higher mean daily dose of corticosteroids (p < 0.001). In the subgroup analysis of RA patients with ILD, 28 patients (36.4%) died during follow-up. Multivariate analysis revealed that older age at the time of ILD diagnosis was significantly associated with mortality. Usual interstitial pneumonia (UIP) subtype on high-resolution computed tomography (HRCT) was also suggested as a poor prognostic factor.@*CONCLUSIONS@#The survival of RA patients with ILD is adversely affected by age at the time of ILD diagnosis. RA-ILD patients diagnosed after age 65 or with a UIP subtype on HRCT may have a poor prognosis.
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BACKGROUND/AIMS@#This study aimed to investigate the inf luence of poor sleep quality on clinical features of primary Sjögren’s syndrome (pSS).@*METHODS@#Sleep quality was cross-sectionally assessed using the Pittsburgh Sleep Quality Index (PSQI), and demographic, clinical, and laboratory data were collected from 115 Korean patients with pSS. The patients completed questionnaires on the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI), quality of life (EuroQOL five dimensions questionnaire [EQ-5D]), fatigue (fatigue severity score [FSS]), and depression (Beck Depression Inventory [BDI] II]). Symptoms and patient global assessment (PGA) were evaluated with a 100-mm visual analogue scale (VAS). The EULAR sicca score (ESS), ESSPRI, and EULAR SS Disease Activity Index (ESSDAI) were calculated at study enrollment.@*RESULTS@#Fifty-three patients (46.1%) had poor sleep quality and 32.4% of 71 patients without depression were poor sleepers. Poor sleepers had a significantly lower EQ-5D or ESSDAI and a significantly higher FSS, BDI-II, PGA, ESS, ESSPRI, or VAS scores for extra-glandular symptoms than good sleepers. Neutrophil and lymphocyte counts were significantly higher and immunoglobulin G levels tended to decrease in poor sleepers. Additionally, PSQI was negatively correlated with EQ-5D and ESSDAI and positively with ESS, FSS, BDI-II, PGA, VAS scores for their symptoms, and ESSPRI. Multivariate analysis revealed that poor sleep quality remained the independent determinants of the unsatisfactory symptom state (ESSPRI ≥ 5).@*CONCLUSIONS@#Our results showed that poor sleep quality could significantly affect the patient-oriented outcomes and physician-reported activity index of pSS patients through the various effects of sleep quality on the psychological or somatic symptoms and the immune system.
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BACKGROUND: We aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification. METHODS: Patients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals. RESULTS: The study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis. CONCLUSION: In Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.
Subject(s)
Humans , Arthritis , Arthrocentesis , Classification , Gout , Mexico , Netherlands , Rheumatic Diseases , Rheumatology , Sensitivity and Specificity , Synovial Fluid , Uric AcidABSTRACT
Follicular bronchiolitis (FB) is an uncommon pulmonary lymphoproliferative disorder that is characterized by the presence of peribronchiolar hyperplastic lymphoid follicles with reactive germinal centers. FB could be associated with systemic illnesses including immunodeficiency, infection, and autoimmune diseases. In Korea, a single case of FB with rheumatoid arthritis was recently described but there has been no report on FB associated with other rheumatic diseases. Herein, we describe the first case of FB presenting nodular ground-glass opacities (GGO), which mimicked lung cancer, in patients with primary Sjögren's syndrome (SS). The differential diagnosis of nodular GGO lesions should include FB although it is a rare manifestation in SS patients.
Subject(s)
Humans , Arthritis, Rheumatoid , Autoimmune Diseases , Bronchiolitis , Diagnosis, Differential , Germinal Center , Korea , Lung Diseases , Lung Neoplasms , Lung , Lymphoproliferative Disorders , Rheumatic DiseasesABSTRACT
OBJECTIVE: To investigate longitudinal changes in the European League Against Rheumatism (EULAR) Sjögren's syndrome patient reported index (ESSPRI) and to study the clinical features associated with favorable ESSPRI changes in primary Sjögren's syndrome (pSS). METHODS: At baseline and after a median period of 6.6 years, 41 pSS patients were evaluated using the ESSPRI, EULAR Sjögren's syndrome disease activity index (ESSDAI), short-form 36, xerostomia inventory (XI), and visual analog scale (VAS) scores for symptoms. The favorable subgroup included patients who were stable or showed improved to satisfactory symptom status (ESSPRI<5) and the unfavorable subgroup included those with stable or worsening to an unsatisfactory symptom status (ESSPRI ≥5). RESULTS: Median ESSPRI increased from 4.11 to 5.33 (p<0.05), although XI scores (p=0.01) and oral dryness (p<0.05) were significantly decreased. Serum immunoglobulin G level was significantly reduced (p<0.001) but ESSDAI scores were unchanged. Six (14.6%) patients showed clinical improvement in ESSDAI, and 11 (26.8%) showed improvement in ESSPRI. On comparing the favorable (n=17) and unfavorable (n=24) subgroups, the former exhibited significantly lower VAS scores for sicca and depression and XI and ESSPRI scores at baseline (all p<0.05) and more lacrimal flow (p<0.05). The favorable subgroup received a significantly lower cumulative dose of pilocarpine and glucocorticoids (both p<0.05). CONCLUSION: About 25% of pSS patients showed clinically significant ESSPRI improvement and about 40% showed a favorable ESSPRI course. Because the favorable subgroup had more lacrimal flow and less sicca symptoms at baseline, long-term patient-derived outcomes could depend on residual exocrine function at pSS diagnosis.
Subject(s)
Humans , Depression , Diagnosis , Glucocorticoids , Immunoglobulin G , Patient Outcome Assessment , Pilocarpine , Quality of Life , Rheumatic Diseases , Visual Analog Scale , Xerophthalmia , XerostomiaABSTRACT
BACKGROUND/AIMS: For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population. METHODS: Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study. RESULTS: Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients (p 10 and less common (13.0%) with baseline mSASSS = 0. CONCLUSIONS: In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.
Subject(s)
Humans , Baths , Disease Progression , Spine , Spondylitis, Ankylosing , ThoraxABSTRACT
Idiopathic hypereosinophilic syndrome (IHES) is a rare disease that is characterized by otherwise unexplained persistent eosinophilia and organ damage caused by eosinophilic infiltration. Its manifestations are highly variable but clinically apparent arthritis is uncommonly observed. Although Korean cases of severe eosinophilia in patients with rheumatoid arthritis (RA) or IHES concurrent with RA have been published, there are no reports of IHES with joint involvement. This paper reports a case of IHES presenting with persistent peripheral eosinophilia, fever, skin rash, multiple lymphadenopathy, and polyarthritis, including the distal interphalangeal joints of the hands.
Subject(s)
Humans , Arthritis , Arthritis, Rheumatoid , Cyclosporine , Eosinophilia , Eosinophils , Exanthema , Fever , Finger Joint , Hand , Hypereosinophilic Syndrome , Joints , Lymphatic Diseases , Rare DiseasesABSTRACT
OBJECTIVE: This study examined the anti-inflammatory and chondroprotective effects of compound K (CK), a ginsenoside metabolite, on chondrocytes from osteoarthritis (OA) patients following stimulation with interleukin (IL)-1β. METHODS: Articular cartilage samples were obtained from six OA patients undergoing total knee replacement surgery. Nitric oxide (NO) production was measured by the Griess reaction. Subsequently, the mRNA and protein levels of matrix metalloproteinases (MMPs), inducible NO synthase (iNOS), and mitogen-activated protein kinases (MAPKs) were examined by a reverse transcription-polymerase chain reaction and western blot analysis. Cartilage degradation was assessed using a glycosaminoglycan (GAG) assay. RESULTS: CK inhibited IL-1β-induced NO production and iNOS expression in a dose-dependent manner. In addition, it inhibited the IL-1 β-stimulated release of MMP-1, -3, and -13 and tissue inhibitor of matrix metalloproteinase-1 from OA patient chondrocytes. In addition, CK effectively suppressed the IL-1β-induced phosphorylation of p38, extracellular signal-regulated kinase-1/2, and c-Jun N-terminal kinase MAPKs. Moreover, the IL-1β-mediated release of GAG was inhibited by CK in a dose-dependent manner. CONCLUSION: CK inhibited the IL-1β-induced expression of inflammatory mediators and MMPs by, at least in part, inhibiting MAPK activation, and has potential as a therapeutic agent for the treatment of OA.
Subject(s)
Humans , Arthroplasty, Replacement, Knee , Blotting, Western , Cartilage , Cartilage, Articular , Chondrocytes , Ginsenosides , Interleukin-1 , Interleukins , JNK Mitogen-Activated Protein Kinases , Matrix Metalloproteinase 1 , Matrix Metalloproteinases , Mitogen-Activated Protein Kinases , Nitric Oxide , Nitric Oxide Synthase , Osteoarthritis , Panax , Phosphorylation , Protein Kinases , RNA, MessengerABSTRACT
Takayasu arteritis (TAK) is a chronic inflammatory disease characterized by granulomatous vasculitis of the aorta and its major branches. The rarity of the disease along with its heterogeneous clinical presentation typically lead to late diagnosis and delayed treatment. Furthermore, clinical and serological indices for monitoring disease activity are suboptimal, with no definitive evidence supporting therapeutic approaches in TAK. Nevertheless, there have been recent advances in disease assessment with new scoring systems (Indian Takayasu Arteritis Score), biomarkers including pentraxin 3 and soluble human leukocyte antigen-E, and imaging modalities such as 18F-fluorodeoxyglucose-positron emission tomography. Most of the new information for management of TAK has come from increasing experience with biological agents, such as tumor necrosis factor inhibitors and tocilizumab, used in the treatment of resistant TAK. A number of potential new therapeutic targets that may be useful for the treatment of TAK have been reported, and randomized controlled trials are needed to establish optimal therapeutic approaches
Subject(s)
Humans , Aorta , Biological Factors , Biomarkers , Delayed Diagnosis , Diagnosis , Leukocytes , Takayasu Arteritis , Tumor Necrosis Factor-alpha , VasculitisABSTRACT
BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSIONS: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.