Ryota Hara

Application of a new immunohistology scoring system (IH score): analysis of TNF-α in synovium related to disease activity score in infliximab-treated patients with rheumatoid arthritis.

Abstract Objectives. This study aimed to analyze the relationship between the expression of tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) in synovium and the disease activity score (DAS) 28 (C-reactive protein, CRP) in treatment of infliximab for rheumatoid arthritis (RA). Methods. Synovial tissues were obtained from 16 infliximab-treated patients and assessed for TNF-α and IL-6 with a new immunohistology (IH) scoring system. The validation of IH score was performed and applied for the analysis of correlation between synovial TNF-α or IL-6 and DAS28 (CRP) in addition to Rooney score. Results. The IH score had high internal validity; the IH score of TNF-α strongly correlated with serum CRP and matrix metalloprotease-3 (MMP-3), as well as DAS28 (CRP) and the Rooney score. IL-6 did not correlate with DAS28 (CRP). Conclusions. This study indicates that the IH score is useful as a new procedure to assess the cytokine expression easily and TNF-α in synovium correlates with disease activity in patients with RA treated with infliximab.

Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study-

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.

Sonographic measurements of low-echoic synovial area in the dorsal aspect of metatarsophalangeal joints in healthy subjects

Abstract Introduction. Assessment of synovitis in the metatarsophalangeal (MTP) joints with ultrasound has been shown to improve the accuracy of assessment of rheumatoid arthritis (RA). However, the presence of intraarticular low-echoic synovial area (LESA) in the MTP joints in healthy subjects complicates the sonographic assessment of these joints. Method. Healthy subjects with no arthritic symptoms in their MTP joints were recruited. All subjects completed a questionnaire and underwent physical examination and sonographic assessment. LESAs in the dorsal aspect of all MTP joints were measured in the longitudinal view. Results. One thousand non-arthritic MTP joints in 100 healthy subjects (female 73, mean age 41.0 years old) were evaluated. Measurable LESAs were identified in all joints assessed. Mean length of LESA in each of the 1st–5th MTP joints was 17.8, 13.9, 11.9, 10.6, and 9.2 mm, respectively, whereas mean thickness was 2.4, 2.4, 1.8, 1.2, and 0.8 mm, respectively. Multivariate linear regression models identified the difference between 1st and 5th MTP joints as the most independently influential factor on the measurement of LESA. Conclusions. Our data provide the normal reference values for the measurements of LESA in Japanese, which should be taken into consideration when the synovitis in MTP joints is evaluated with ultrasound.

Subclinical articular involvement in primary Sjögren's syndrome assessed by ultrasonography and its negative association with anti-centromere antibody

Objectives. To evaluate the subclinical articular involvement in patients with primary Sjögrens syndrome (pSS) using musculoskeletal ultrasound (MSUS), and to correlate the findings with laboratory results and clinical manifestations. Methods. Forty-eight consecutive patients with pSS were enrolled. The bilateral metacarpophalangeal, proximal interphalangeal, and interphalangeal joints were examined using MSUS, and the synovial hypertrophy and power Doppler signal were recorded for each joint using semi-quantitative scores (0 = normal, 1 = mild change compared with undamaged joint, 2 = moderate change, and 3 = severe change). Results. Mild or moderate synovial hypertrophy was found in 151 (15.7%) and 2 (0.2%) out of 960 hand joints, respectively, and power Doppler signals were present in 19 (2.0%) of the 960 joints. While anti-centromere antibody (ACA) was found in 10 patients (20.8%), none of the patients with MSUS-confirmed synovitis was positive for ACA. No other autoantibodies, laboratory tests, or clinical manifestations correlated with MSUS-confirmed synovitis. Conclusion. MSUS is useful for detecting subclinical synovitis in pSS patients. MSUS showed that ACA-positive pSS patients had a low prevalence of synovitis.

AB0310 Prognostic Factor for Forefoot Deformity in Early Rheumatoid Arthritis

Background Disease activity score (DAS) 28 and simplified disease activity index (SDAI) and clinical disease activity index (CDAI) are often used for clinical assessment, and these criteria dose not include assessment of joints in the feet. Residual synovitis of the MTP joints and various factors such as inflammatory marker, drugs and weght-bearing possibly cause various deformities of the forefoot and lead to functional, cosmetic problems. Objectives To determine prognostic factors of forefoot deformity in early rheumatoid arthritis (RA). Methods Twenty-four outpatients with RA before tight control were enrolled. At baseline, the mean age of patients was 57.8 years and the mean disease duration was 11.2 months. The mean body mass index (BMI) was 22.0 kg/m2. The mean DAS28, SDAI and modified health assessment questionnaire (mHAQ) at baseline was 4.84, 21.9 and 0.29. The mean CRP and MMP-3 was 1.7 mg/dl and 153 ng/ml. Eleven patients (46%) were treated with conventional synthetic disease modified anti-rheumatic drugs (csDMARDs) and 8 patients (33%) were treated with glucocorticoids (GCs, mean dose of prednisolone 5.6mg). Nine patients (38%) were treated biological agents at final follow up. As ultrasonographic assessment, bilateral first IP joint, the second to fifth PIP joint, the first to fifth MCP and MTP joints were assessed by semi-quantitative assessment (0 - 3) using power Doppler ultrasonography (PDUS). The sum score of all joints and MTP joints was used as total PDUS (TPD) and foot PDUS (FPD). Radiographic damages of feet were evaluated by using van der Heijde modified total sharp score (footTSS, 0 - 168). Radiographic forefoot deformities were evaluated by using hallux valgus angle (HV), 1st to 2nd metatarsal angle (M1M2) and 1st to 5th metatarsal angle (M1M5). Both radiographic assessment were performed at baseline and final follow up (mean 2.7 years), and the sum of these angle (HV + M1M2 + M1M5) was used as total deformity score (TDS). Results Twenty-one (87.5%) and 18 (75%) patients achieved DAS28 and SDAI remission after tight control. At final follow up, all deformity angle were significantly progressed and mean ΔHV, ΔM1M2, ΔM1M5 and ΔTDS was 3.58, 2.29, 3.88 and 9.75 respectively. ΔTDS were not correlated with ΔfootTSS (ρ=0.09, p=0.68). DAS28, SDAI, TPD, FPD, CRP, MMP-3 and BMI were not correlated with ΔTDS, whereas univariate linear analysis identified significant correlation with GCs and ΔTDS (p=0.009), and multiple regression analysis revealed GCs was a independent risk for forefoot deformity (p=0.01). Conclusions Forefoot deformity in RA progressed even if clinical remission was achieved. Baseline prognostic factor for forefoot deformity in early RA was oral low dose GCs in the early stage of treatment. Disclosure of Interest None declared

AB0802 A Patients Preference Survey for Osteoporosis Medication on 679 Patients: Monthly Drug Regimen Can be the Best for the Adherence

Background Bisphosphonates are the first-line therapy for osteoporosis treatment though the long-term persistence and adherence to bisphosphonates remain low (1-2). This medication noncompliance has serious consequences as it is associated with higher morbidity and mortality (3-6). Objectives To explore patient preferences for the osteoporosis medication, we performed a cross sectional survey. Methods A questionnaire for the persistence and adherence was distributed to all patients and the attending doctor, who treated osteoporosis in our university hospital, the university teaching hospitals, and the related clinics. The questionnaire was designed that one form contained information from both patients and the attending doctors. A total of 679 questionnaire out of 765 were completed, and the data were evaluated. The medication noncompliance was assessed, and Cox proportional hazards regression was used to estimate the association between treatment regimens and “forgetting to take a medication”. For subgroup analysis between young old (<65 yr) and old (over 65yr) generation, the chi-square test was applied. To evaluate (dis)similarity among factors which affect the forgetting, type IV quantification theory was applied. Results 556 women and 83 men were enrolled; 30% of the patients were in the 80s and 46% were in the 70s. All patients assumed oral bisphosphonates. 66% of the patients were assuming weekly bisphosphonates, 24.4% were assuming monthly bisphosphonates, and 8.7% were assuming daily bisphosphonates. Interestingly, 42 patients answered to assume daily bisphosphonates while the attending doctor reported to prescribe the daily bisphosphonates to 78 patients. In the multivariate logistic regression model, compared with daily bisphosphonates, weekly bisphosphonates was significantly associated with “forgetting to take a medication” (odds ratio 2.01 [95% CI 1.10-3.65]; P<0.05). In the subgroup analysis, the “forgetting frequency” showed no differences, but the young old generation had a tendency to have difficulty (“hassle”) for the medication. A proportion of patients who preferred less frequent dosing regimen was significantly larger in the young old than old generation (P<0.05). Conclusions Weekly drug regimen was significantly associated with incompliance. Considering that less number of patients answered “hassle” for monthly drug regimen, monthly regimen can be the best for adherence among the three regimens. Less frequent dosing regimen was further required especially in young old generation. References Imaz et al.Osteoporos Int. 2010;21:1943–1951. Kothawala et al.Mayo Clin Proc. 2007;82:1493–1501. Ryg et al. J Bone Miner Res. 2009;24:1299-307. FitzGerald et al. J Bone Miner Res. 2012;27:1907-15. Gehlbach S et al. J Bone Miner Res. 2012;27:645-53. Cameron et al. J Bone Miner Res. 2010;25:866-72. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1628

FRI0277 Predicting Future Response to Tumor Necrosis Factor Inhibitors by the Distribution of Affected Joints in Rheumatoid Arthritis Patients

Background Achieving remission is essential for avoiding joint destruction and disability in patients with rheumatoid arthritis (RA). Tumor necrosis factor inhibitors (TNFi) therapies represent an important advancement in therapy for RA. However, there remains a proportion of patients who do not improve despite TNFi therapies. Recently, Terao et al. (1) analyzed the distribution of affected joints in the 28 joints in patients with RA and showed that RA patients can be categorized into three subgroups based on their affected joints (1: PIP joints dominant, 2: MCP joints dominant, and 3: large joints with wrist joints dominant). Nevertheless, it remains obscure whether these three subgroups were correlated with treatment response. Objectives To analyze the prognostic significance of data collected at starting TNFi, especially the distribution of affected joints, to predict remission in RA patients at week 16. Methods Data from 62 TNFi-treated patients with RA at the baseline were used as variables to predict remission. The disease status at the baseline and week 16 was assessed using the disease activity score (DAS 28) and patients achieving remission at week 16 were identified according to EULAR criteria (DAS 28 <2.6). The mean age of patients was 57.6 and the mean disease duration was 9.7 years. The mean disease activity at the baseline was 4.93 and 22.7 for DAS28 and simplified disease activity index (SDAI), respectively. The mean modified health assessment questionnaire (mHAQ) was 0.658. Thirty-eight patients (61%) were naïve to biologic agents. Fifteen (24%), 16 (26%), and 31 (50%) patients were treated with etanercept, adalimumab, and golimumab, respectively. Forty-eight (77%) and 30 (48%) patients were treated with methotrexate (MTX) and glucocorticoids (GC) concurrently. All of the patients were classified into 3 groups according to their affected joints which have tenderness or swelling, that is, 1: PIP joints dominant (PIPd) group, 2: MCP joints dominant (MCPd) group, and 3: large joints with wrist joints dominant (L-Wd) group. The correlation of baseline characteristics with achievement of remission at week 16 was explored by multivariate logistic regression analysis. Results The patients were classified into 11 (18%) of PIPd group, 19 (31%) of MCPd group, and 32 (52%) of L-Wd group according to their affected joints. Univariate analyses revealed that patients who achieved remission showed significantly lower levels of DAS28, mHAQ, ESR, and CRP, and shorter disease duration than those without remission. It was also disclosed that patients in PIPd group were more likely to achieve remission than patients in MCPd group or L-Wd group. The baseline characteristics including concurrent use of MTX and/or GC, previous biologics therapy, tender joint count, and swollen joint count were not associated with response to TNFi. Among the baseline characteristics, lower levels of ESR and belonging to PIPd group were independently correlated with achievement of remission in multivariate analysis (p=0.012 and 0.028, respectively). Conclusions We suggested that RA patients predominantly affected with PIP joints were likely to achieve remission in response to TNFi. The distribution of affected joints could predict future response to TNFi in RA patients. References Terao C et al. PLoS One. 2013; 8: e59341. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1980