Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

OBJECTIVES: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both. RESULTS: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models. CONCLUSIONS: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

Changes in the incidence of cervical lesions owing to the development of rheumatoid arthritis treatment and the impact of cervical lesions on patients' quality of life.

Objectives: To clarify changes in the incidence of cervical lesions in rheumatoid arthritis (RA) patients with advanced treatment and the impact of cervical lesions on the patients' quality of life (QOL).Methods: Incidence of radiographic cervical lesions in 1333 RA patients in 2015 was compared with that in our 1999 survey. The association between cervical lesions and QOL evaluated using three different patient-based questionnaires was also analyzed.Results: The incidence of atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS) in 2015 decreased by 50%, 75%, and 5%, respectively, compared to the 1999 survey. Although QOL, evaluated using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ; specific to myelopathy), deteriorated as the cervical lesion progressed, there was no association between cervical lesion progression and QOL evaluated using the Short Form-8™ (SF-8™; comprehensive health-related QOL). Cervical lesion progression was also associated with QOL deterioration evaluated using the Health Assessment Questionnaire Disability Index (HAQ-DI; specific to RA), but age and disease duration had stronger influences.Conclusion: The incidence of cervical lesions decreased in 2015 compared to 1999. Cervical lesion progression may be associated with QOL deterioration due to myelopathy. Age and disease duration have more impact on disease-specific QOL.

Prevalence of and factors associated with dysfunctional low back pain in patients with rheumatoid arthritis.

PURPOSE: To investigate the prevalence of and factors associated with dysfunctional low back pain (LBP) in patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study included 1276 RA outpatients from two hospitals. The Roland-Morris Disability Questionnaire was used to address the functional-dysfunctional state criterion. Clinical variables, such as medical status, disease activity, bone mineral density, and spinopelvic alignment parameters, were compared between patients with and without dysfunctional LBP. RESULTS: Mean age and disease duration were 64.6 and 13.4 years, respectively; the prevalence of dysfunctional LBP was 32.8%. On univariate analysis, significant differences existed in many variables, except sex, body weight, C-reactive protein (CRP) level, and prevalence of biological agent users, between patients with and without dysfunctional LBP. Multivariate logistic regression analysis revealed body mass index (BMI; odds ratio [OR], 1.116; P < 0.001), onset age of RA (OR, 1.020; P = 0.020), disease duration of RA (OR, 1.043; P < 0.001), methotrexate (MTX) use (OR, 0.609; P = 0.007), vertebral fractures (OR, 2.189; P = 0.001), vertebral endplate and/or facet erosion (OR, 1.411; P = 0.043), disease activity score (DAS) in 28 joints-CRP (DAS-28CRP) (OR, 1.587; P = 0.001), pelvic tilt (PT; OR, 1.023; P = 0.019), and sagittal vertical axis (SVA; OR, 1.007; P = 0.043) as associated factors. CONCLUSION: The factors associated with dysfunctional LBP in patients with RA were more vertebral fractures, higher DAS-28CRP, vertebral endplate and/or facet erosion, higher BMI, longer disease duration, greater PT, older onset age, greater SVA, and less MTX use. Strictly controlling patients' body weight and disease activity with MTX and avoiding spinopelvic malalignment through vertebral fracture prevention are important. These slides can be retrieved under Electronic Supplementary Material.

Clinical outcome of Niigata-Senami-Kyocera modular unconstrained total elbow arthroplasty for destructive elbow in patients with rheumatoid arthritis.

BACKGROUND: Total elbow arthroplasty (TEA) is a treatment option for destructive and painful unstable elbows in rheumatoid arthritis (RA). We evaluated the clinical outcomes of unconstrained TEA (Niigata-Senami-Kyocera modular system). METHODS: Seventy-five unconstrained TEAs were performed in patients with RA (mean age, 64 years; age range, 41-79 years; follow-up rate, 97%). Outcome measures included the Japanese Orthopaedic Association (JOA) functional evaluation score for the elbow joint (JOA score), range of motion, and arc. Bone ingrowth of the humeral component, the incidence of stress shielding around the humeral component, the incidence of loosening of the ulnar component, complications, and the survival rate were investigated. RESULTS: The mean follow-up period was 5.2 years (range, 2-11.3 years). The JOA elbow score improved from 42 points preoperatively to 87 points postoperatively (P < .0001). Each specified item improved (P < .0001). Flexion improved from 109° to 134°; the flexion-plus-extension arc improved from 70° to 108° (P < .0001). Bone ingrowth of the humeral implant was achieved in all elbows. Stress shielding of the humeral component was detected in 11 elbows (14%); it was significantly higher in 10- and 9-mm-diameter humeral stems than in 8-mm-diameter humeral stems (P = .008). The ulnar component showed no loosening except in 1 elbow owing to infection. Complications were detected in 9 patients (9 elbows, 12%): periprosthetic infection (3), fracture (4), and dislocation (2). The survival rates were 97% at 5 years and 93% at 10 years postoperatively. DISCUSSION: The Niigata-Senami-Kyocera modular system for patients with RA showed good outcomes. Stress shielding can be avoided by using an 8-mm-diameter humeral stem.

Incidence of hepatitis B virus reactivation in patients with resolved infection on immunosuppressive therapy for rheumatic disease: a multicentre, prospective, observational study in Japan.

BACKGROUND: Although the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial. OBJECTIVES: To investigate the incidence and risk factors for HBV reactivation in patients with RD. METHODS: We performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded. RESULTS: Among 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3-182 months; median, 66 months). CONCLUSIONS: The incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

Reliability, validity, and responsiveness of the Japanese version of the patient-rated elbow evaluation.

BACKGROUND: The patient-rated elbow evaluation (PREE) is a joint-specific, self-administered questionnaire consisting of a pain scale (PREE-P) and a functional scale (PREE-F), the latter consisting of specific function (PREE-SF) and usual function (PREE-UF). The purpose of this study was to cross-culturally adapt the PREE into Japanese (PREE-J) and to test its reliability, validity, and responsiveness. METHODS: A consecutive series of 74 patients with elbow disorder completed the PREE-J, the Japanese version of the disabilities of the arm, shoulder, and hand (DASH-JSSH) questionnaire, and the official Japanese version of the 36-Item Short-Form Health Survey (SF-36). Of the 74 patients, 53 were reassessed for test-retest reliability 1 or 2 weeks later. Reliability was investigated in terms of reproducibility and internal consistency. The validity of the PREE-J was examined by factor analysis, and correlation coefficients were obtained using the PREE-J, DASH-JSSH, and SF-36. Responsiveness was examined by calculating the standardized response mean (SRM) and effect size after elbow surgery in 53 patients. RESULTS: Cronbach's α coefficients for PREE-P, PREE-F, and PREE were 0.92, 0.97, and 0.97, respectively, and the corresponding intraclass correlation coefficients were 0.92, 0.93, and 0.94, respectively. Unidimensionality of PREE-P and PREE-F was confirmed by factor analysis. The coefficients of correlation between PREE-P and PREE-F or DASH-JSSH were 0.81 and 0.74, respectively; that between PREE-F and DASH-JSSH was 0.86, and those between DASH-JSSH and PREE-SF or PREE-UF were 0.85 and 0.82, respectively. Moderate correlation was observed in "physical functioning" for SF-36 and PREE-F (r = -0.69) or PREE (r = -0.68). The SRMs/effect sizes of PREE-P (1.31/1.32) or PREE (1.28/1.12) were more responsive than the DASH-JSSH (0.99/0.85), "bodily pain" (-1.15/-1.43), and "physical functioning" (-0.70/-0.44) in SF-36. CONCLUSION: The PREE-J represents a reliable, valid, and responsive instrument and has evaluation capacities equivalent to those of the original PREE.

Risk stratification and clinical course of hepatitis B virus reactivation in rheumatoid arthritis patients with resolved infection: final report of a multicenter prospective observational study at Japanese Red Cross Hospital.

BACKGROUND: The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. METHODS: HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. RESULTS: Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive < 2.1 log copies/mL during the observation period. We designed the following scoring system: HBV reactivation risk score = 1 × (age > 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. CONCLUSIONS: Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

Abatacept in combination with methotrexate in Japanese biologic-naive patients with active rheumatoid arthritis: a randomised placebo-controlled phase IV study.

OBJECTIVES: To evaluate efficacy and safety of abatacept+methotrexate (MTX) in biologic-naive, anticitrullinated protein antibody (ACPA)-positive Japanese patients with active rheumatoid arthritis (RA) and early erosion versus placebo+MTX. METHODS: In this phase IV, multicentre, double-blind study (NCT01758198), patients were randomised (1:1) to receive intravenous abatacept (~10 mg/kg) or placebo, plus MTX (≥6 mg/week). Primary efficacy objectives were to compare American College of Rheumatology 20 (ACR20) response rates at week 16 and mean change from baseline in van der Heijde-modified total Sharp score (vdH-mTSS) at week 24 between abatacept+MTX and placebo+MTX groups. RESULTS: Overall, 203 and 202 patients received abatacept+MTX and placebo+MTX, respectively. At week 16, ACR20 response rates were higher in the abatacept (75.4%) versus placebo group (27.7%; p<0.001). Mean change from baseline in vdH-mTSS at week 24 was 0.84 in the abatacept and 1.26 in the placebo group (p=0.017). Radiographic non-progression rates (change in vdH-mTSS≤smallest detectable change (2.4)) were 88.1% and 75.4% in abatacept and placebo groups, respectively. Adjusted mean change from baseline in Disease Activity Score 28 (C-reactive protein) (DAS28 (CRP)) at week 16 demonstrated a numerically greater reduction in the abatacept versus placebo group. Proportions of patients with DAS28 (CRP), Simplified Disease Activity Index and Clinical Disease Activity Index remission up to week 52 were higher in the abatacept versus placebo group. The abatacept safety profile was consistent with previous observations. CONCLUSIONS: Compared with MTX alone, abatacept+MTX improved clinical symptoms and inhibited structural damage progression in ACPA-positive, Japanese patients with RA, early erosion and inadequate response to MTX.

Tight control is important in patients with rheumatoid arthritis treated with an anti-tumor necrosis factor biological agent: prospective study of 91 cases who used a biological agent for more than 1 year.

The purpose of this study is to identify the factors that require arthroplasty due to the progression of joint destruction, even when an anti-tumor necrosis factor (TNF) biological agent is used for rheumatoid arthritis (RA). Among 91 cases that used the anti-TNF biological agent for more than 1 year, two groups of 21 cases that resulted in arthroplasty (surgery group) and 70 cases that did not result in arthroplasty (non-surgery group) were compared and examined. When the anti-TNF biological agent was first administered, disease activity and internal use of glucocorticoid (PSL) were not different in these two groups. The average DAS28-CRP(4) (disease activity score including a 28-joint count/C-reactive protein) (p < 0.001) and the amount of internal use of PSL (p < 0.05) were significantly decreased in the non-surgery group compared with the surgery group at the final survey. To inhibit the need for joint surgery in patients using the anti-TNF biological agent, it is important to maintain tight control over RA activity.

Risk factors for vertebral fracture in menopausal or postmenopausal Japanese women with rheumatoid arthritis: a cross-sectional and longitudinal study.

The occurrence of vertebral fracture was examined cross-sectionally and longitudinally over a 4-year interval in 117 menopausal and postmenopausal Japanese women with rheumatoid arthritis (RA), whose ages ranged from 50 to 64 years. Patients treated with bisphosphonate were excluded. Vertebral fracture was diagnosed by lateral thoracic and lumbar spine radiography at the start and end of a 4-year period. Bone mineral density (BMD) at L2-L4 according to dual-energy X-ray absorptiometry (DXA), the administration of corticosteroids or methotrexate, and urinary excretion of N-telopeptide of type I collagen (NTx) were also recorded. In the cross-sectional study, the prevalence of vertebral fracture in the initial radiographs of RA patients was 21%, while it was 5% in healthy age-matched controls. Among RA patients treated with corticosteroids, 33% had vertebral fracture, which was a significantly higher prevalence than that in RA patients without steroid administration. In the longitudinal study, vertebral fracture prevalence was also increased in patients more than 60 years old. RA patients having steroid treatment and a BMD/YAM (young adult mean) ratio below 70% had higher risk of vertebral fracture than patients with a BMD/YAM ratio of 70%-80%, which in turn exceeded the risk with a BMD of 80% or more. No adverse effect of low-dose methotrexate on vertebral fracture was found. Urinary NTx was high in RA patients, as reported previously, and did not differ between patients with or without new fracture after 4 years. In conclusion, Japanese RA patients more than 60 years old who were treated with corticosteroid or had a BMD below 80% had high risk of vertebral fracture.

Fenofibrate inhibits reactive amyloidosis in mice.

OBJECTIVE: To examine the effects of the lipid-lowering agent fenofibrate on experimental AA amyloidosis and on serum amyloid A (SAA) levels. METHODS: Fenofibrate was administered orally in a mouse model of amyloidosis, which is induced by injections of amyloid-enhancing factor and Freund's complete adjuvant. Fenofibrate was given for 3 weeks, including a 1-week course before induction of amyloidosis. Splenic amyloid deposits were evaluated histologically, and SAA levels were measured. RESULTS: Fenofibrate inhibited the formation of splenic amyloid deposits and suppressed the elevation of SAA levels. CONCLUSION; Fenofibrate inhibits experimental amyloidosis by reducing levels of the precursor SAA.

Validation of a Japanese patient-derived outcome scale for assessing total knee arthroplasty: comparison with Western Ontario and McMaster Universities osteoarthritis index (WOMAC).

We have developed a Japanese self-administered questionnaire based on an English version of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) to measure subjective function and pain status of patients who undergo a total knee arthroplasty procedure. Using multiple international cohorts, the performance of the developed Japanese scale was compared to the results of the WOMAC in the United Kingdom, United States, Canada, and Australia. The developed scale showed a comparable level of internal consistency and construct/criterion validity. The responsiveness of the scale was superior to the concurrently measured MOS Short Form 36 Physical Function scale. These results suggest that the developed scale is reliable, valid, and responsive for assessing the effectiveness of total knee arthroplasty in the Japanese context despite the cultural life style differences from Western countries.

Quantitative assessment of hand radiographs of rheumatoid arthritis: interobserver variation in a multicenter radiographic study.

We investigated interobserver variations in the Larsen radiographic scoring method on hand radiographs of rheumatoid arthritis (RA) patients in a multicenter trial and developed a new radiographic scoring method. Thirteen experienced rheumatologists scored 10 representative RA hand radiograms with the Larsen scoring method and clarified the precipitating factors of interobserver variation. Based on this study, it was proved that the ankylotic joint, overlapping joint, and more precise erosive joint are needed for optimal radiographic evaluation. Therefore, we modified the Larsen scoring method on the basis of these precipitating factors and developed a novel radiographic scoring method. Finally, to determine which scoring system was most reliable, the interobserver variation using three methods (original Larsen method, revised Larsen method, our scoring method) were compared by 13 experienced rheumatologists and 13 residents. Our scoring method proved to have simplicity, reliability, and ease of learning. These results suggest that our novel radiological quantitative assessment method has useful applications for clinical studies in patients with RA.