Golimumab reduces disease activity of rheumatoid arthritis for 1 year and strongly inhibits radiographic progression in Japanese patients: partial but detailed results of the GO-FORTH and GO-MONO studies

The objective of this study is to evaluate the efficacy of golimumab (GLM) in Japanese patients with active rheumatoid arthritis (RA) for 1 year. Nineteen patients were enrolled; 9 were randomized to the placebo (PBO) + methotrexate (MTX), GLM 50 mg + MTX, or GLM 100 mg + MTX therapy group; and 10 were randomized to the PBO, GLM 50 mg, or GLM 100 mg therapy group. One patient in the GLM 100 mg + MTX therapy group with median values from the GO-FORTH study was added. Data were evaluated by assessing the changes in DAS28-ESR, Health Assessment Questionnaire Disability Index (HAQ-DI), and total Sharp score (TSS) at week 52. Mean changes in DAS28-ESR in the MTX monotherapy, GLM 50 mg + MTX, GLM 100 mg + MTX, PBO, GLM 50 mg, and GLM 100 mg therapy groups were ?2.70, ?2.57, ?2.27, ?0.60, ?2.53, and ?2.53, respectively; the mean improvements in HAQ-DI were 0.188, 0.708, 0.377, 0.188, 1.042, and 0.625, respectively. The mean changes in TSS were 1.63, ?0.33, ?1.17, 4.25, 1.00, and 1.67, respectively. A significant difference was only observed in the mean TSS change between the PBO + MTX and the GLM 100 mg + MTX groups. However, in terms of mean changes in DAS28-ESR in the combination therapy groups, PBO + MTX therapy seemed to elicit similar results as the GLM 50 mg + MTX and GLM 100 mg + MTX therapies (no significant difference) because all four patients in the PBO + MTX therapy group may have received GLM from week 24 as a crossover. Combined GLM + MTX therapy reduced disease activity and strongly inhibited radiographic disease progression in patients with active RA at week 52.     

Disease activity early in treatment as a predictor of future low disease activity in RA patients treated with iguratimod

Objectives. This retrospective observational study aimed to examine the efficacy of iguratimod with and without concomitant methotrexate (MTX) and to estimate the adequate observational period for predicting low disease activity (LDA) achievement at 24 weeks in patients with rheumatoid arthritis (RA).

Methods. All patients treated with iguratimod were registered in a Japanese multicenter registry. Multivariate analyses were performed to identify predictive factors for LDA achievement at 24 weeks. Receiver operating characteristic (ROC) curve analyses were performed to estimate the association of 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) at each time point with achievement of LDA at 24 weeks and determine a cut-off for DAS28-ESR.

Results. A total of 123 patients were treated with iguratimod with (n = 65) or without (n = 58) MTX. Iguratimod therapy resulted in significant clinical improvement in both groups. Multivariate analysis revealed that DAS28-ESR at each time point was an independent significant predictor of LDA achievement at 24 weeks. Cut-off values of DAS28-ESR at 12 weeks based on ROC curves were 3.2 and 3.6 in patients with and without MTX, respectively.

Conclusions. Iguratimod was effective in RA patients in clinical practice. Our results suggest that 12 weeks may be a sufficient period to judge the medium-term efficacy of iguratimod in patients treated with and without MTX.     

Prediction of DAS28-ESR remission at 6 months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

Abstract

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX.     

Assessment of the effectiveness of golimumab 50-mg and 100-mg regimens in patients with rheumatoid arthritis in daily practice

Abstract

Objectives. To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. Methods. We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. Results. We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. Conclusions. Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice.     

Effectiveness and Safety of Golimumab for Patients ≥75 Years Old with Rheumatoid Arthritis

ObjectiveTreatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p＜0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p＜0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.     

A multi-biomarker disease activity score tracks clinical response consistently in patients with rheumatoid arthritis treated with different anti-tumor necrosis factor therapies: A retrospective observational study

Abstract

Objectives. To assess the ability of a multi-biomarker disease activity (MBDA) score to track clinical response in patients with rheumatoid arthritis (RA) treated with different TNF inhibitors.

Methods. The study included 147 patients who had received adalimumab, etanercept, or infliximab for a year or more, during routine clinical care at the University Hospital of Occupational and Environmental Health, Japan. MBDA scores and clinical measures of disease activity were evaluated at baseline and, after 24 weeks (N = 84) and 52 weeks of treatment. Relationships between the changes (?) in MBDA score and changes in clinical measures or EULAR response categories were evaluated.

Results. The median disease activity was 5.7 by DAS28-ESR and 64 by MBDA score at baseline, and decreased significantly with treatment. ?MBDA scores over 1 year correlated with ?DAS28-ESR (r = 0.48) and ?DAS28-CRP (r = 0.46). Linear relationships between ?MBDA scores and ?DAS28-ESR or ?DAS28-CRP were not significantly different between TNF inhibitors. The MBDA scores declined significantly more in good responders (median change: –29) than moderate (–21), and more in moderate than in non-responders (+ 2), by the EULAR criteria.

Conclusions. MBDA scores tracked disease activity and treatment response in patients with RA treated with three TNF inhibitors. The relationships between ?MBDA scores and ?DAS28-ESR or ?DAS28-CRP were consistent across the three TNF inhibitor groups.     

Tocilizumab is clinically,functionally, and radiographically effective and safe either with or without low-dose methotrexate in active rheumatoid arthritis patients with inadequate responses to DMARDs and/or TNF inhibitors: A single-center retrospective cohort study (KEIO-TCZ study) at week 52

Abstract

Objectives. To explore the effectiveness and safety of tocilizumab (TCZ) with or without methotrexate (MTX) in active rheumatoid arthritis (RA) patients showing inadequate responses to DMARDs and/or TNF inhibitors in clinical practice.

Methods. We observed consecutive 115 RA patients initiating TCZ treatment in Keio University Hospital, dividing them into two groups with (TCZ + MTX group) or without MTX (TCZ group), and evaluated clinical, functional and structural outcomes besides safety at week 52.

Results. Overall mean age, RA duration, and DAS28-ESR were 55.4, 8.4 years, and 5.0, respectively. Proportions of the prior use of TNF inhibitors and concomitant MTX were 45.5% and 57.4%, respectively. Mean dose of concomitant MTX was 8.4 mg/week. Baseline characteristics were comparable between the groups. TCZ improved disease activity measured by DAS28-ESR to 2.1 at week 52 overall, without significant difference between the groups. Clinical (DAS28-ESR < 2.6), functional (HAQ-DI ≤ 0.5), and structural (ΔTSS ≤ 0.5) remission rates in the TCZ group and the TCZ + MTX group were 79.1%/63.8% (P = 0.10), 62.8%/54.4% (P = 0.40), and 70.0%/53.8% (P = 0.61), respectively. Retention rates were 81.0% in the TCZ + MTX group and 88.5% in the TCZ group (P = 0.47). The rate of serious adverse events was comparable between the groups.

Conclusions. TCZ was clinically, functionally, and radiographically effective and safe either with or without low-dose MTX.     

Clinical efficacy,radiographic progression,and safety through 156 weeks of therapy with subcutaneous golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis despite prior methotrexate therapy: final results of the randomized GO-FORTH trial

Objective: To evaluate the safety and efficacy of golimumab?+?methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA).

Methods: Japanese patients with active RA despite MTX were randomized to placebo?+?MTX (Group 1, n?=?88), golimumab 50?mg?+?MTX (Group 2, n?=?86), or golimumab 100?mg?+?MTX (Group 3, n?=?87). Patients with?<20% improvement in swollen/tender joint counts entered early escape at week 16. At week 24, all remaining placebo patients crossed over to golimumab 50?mg. Efficacy assessments included ACR20, DAS28-ESR, and HAQ-DI. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score.

Results: ACR20 response rates in Group 1, Group 2, and Group 3 were 67.9, 86.1, and 82.4%, respectively, at week 52 and were maintained through week 104 (87.1, 94.0, and 88.7%) and week 156 (97.1, 94.1, and 89.5%). Proportions of patients with good/moderate DAS28-ESR response or clinically meaningful improvement in HAQ-DI were also maintained through week 156. The majority of patients did not experience radiographic progression through week 156. Among 257 golimumab-treated patients, 251 (97.7%) had?≥1 AE; 54 (21.0%) had?≥1 serious AE through week 156. Infections were the most common type of AE.

Conclusions: Response to golimumab?+?MTX was maintained over 3 years in Japanese patients with active RA despite MTX. Safety results were consistent with the known safety profile of golimumab.     

Postmarketing surveillance evaluating the safety and effectiveness of golimumab in Japanese patients with rheumatoid arthritis

Objectives: The purpose of this study was to evaluate the real-world safety and effectiveness of golimumab (GLM) in Japanese patients with rheumatoid arthritis.

Methods: A postmarketing surveillance of 5154 patients was conducted with a follow-up duration of at least 24 weeks. Patients were divided into four groups based on the initial treatment: 50?mg or 100?mg of GLM with concomitant use of methotrexate (MTX) and 50?mg or 100?mg of GLM monotherapy. Patient characteristics at baseline, safety and effectiveness were assessed for each group.

Results: Over 70% of patients received 50?mg of GLM with concomitant MTX, and approximately, 20% received monotherapy. The incidence rate of adverse events was 45.40 per 100 patient-years. The incidence of adverse events including serious adverse events was comparable across all groups. The proportion of patients showing remission or low disease activity increased from 13.69% to 46.21% at the final evaluation, and no differences were observed in the percentage of remission across the four groups. Concomitant MTX use was associated with higher probability of continuing therapy.

Conclusions: GLM showed effectiveness in Japanese rheumatoid arthritis patients with an acceptable safety profile.     

Discontinuation of infliximab in rheumatoid arthritis patients in clinical remission

Abstract

Biologic drugs are effective but are also expensive, and it is difficult to evaluate the duration of treatment. Infliximab, an anti-TNFα antibody, suppresses arthritic activity and inhibits bone destruction in patients with rheumatoid arthritis (RA). Here, we document that infliximab could be discontinued after clinical remission in RA patients. Among 172 patients with RA who reached clinical remission following infliximab (3 mg/kg) and methotrexate (MTX, >6 mg/w), nine patients with sustained remission discontinued it. Clinical assessment was based on a disease activity score (DAS) that included a 28-joint count/erythrocyte sedimentation rate (DAS28-ESR). The disease was assessed before and after the start of infliximab treatment, and concomitant drug treatment—in the order of corticosteroid, nonsteroidal anti-inflammatory drugs (NSAIDs), and disease-modifying anti-rheumatic drugs (DMARDs) other than MTX—was gradually discontinued. We considered patients for discontinuation of infliximab treatment after remission (DAS28-ESR < 2.6) had been sustained for more than 24 weeks. The nine patients able to discontinue treatment were all females, with a mean age of 53.8 years; eight patients were at stage I or II. The mean duration of disease was 28.7 months, and these patients were on corticosteroid treatment equivalent to a mean of 2.28 mg prednisolone (PSL). These nine patients all met the remission standard—that DAS28-ESR < 2.6 for ≥24 weeks) —and so their treatment with concomitant drugs was discontinued. After the discontinuation of infliximab, the mean period of sustained remission was 14.2 months and the longest period was 29 months. The duration of disease was significantly shorter and the points from Steinbrocker’s stage-classification were significantly lower in the infliximab-discontinued group than in the infliximab-continued group. Strategic reductions and/or discontinuations of concomitant treatment were performed in RA patients who attained clinical remission (DAS28 < 2.6) through treatment with infliximab and MTX. Nine patients successfully discontinued infliximab after maintaining clinical remission for more than 24 weeks. After infliximab was discontinued, clinical remission and suppression of joint destruction were maintained with MTX alone, especially in early RA patients.     

Impact of methotrexate dose on efficacy of adalimumab in Japanese patients with rheumatoid arthritis: Results from registered data analyses

Objective: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16?mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice.

Method: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10?mg/week or more (MTX ≥10?mg group) and <10?mg/week (MTX <10?mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria.

Results: The MTX ≥10?mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10?mg group (26.1%). Multivariate analysis showed that MTX ≥10?mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX ≥10?mg group compared with 52.0% in MTX <10?mg group. Discontinuation of ADA due to adverse events were comparable in the MTX ≥10?mg and MTX <10?mg groups (11.1% vs. 12.0%).

Conclusions: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX ≥10?mg in Japanese RA patients.     

Effectiveness of golimumab for rheumatoid arthritis in patients with an inadequate response to tocilizumab

Objectives: Several biological disease–modifying antirheumatic drugs (bDMARDs) are currently available for the treatment of rheumatoid arthritis (RA). Increasing evidence indicates that second-line bDMARDs are effective for inadequate responders to first-line bDMARDs. However, all previous studies investigated the use of tumor necrosis factor inhibitors (TNFi) as a first-line bDMARD, while investigated the efficacy of second-line bDMARDs after the use of tocilizumab (TCZ), a non-TNFi, as a first-line bDMARD. Thus, we investigated the efficacy of golimumab (GLM) as a second-line bDMARD after treatment with TCZ as a first-line bDMARD.

Methods: The final study population consisted of 26 patients (inadequate responders to TCZ; TCZ group) with moderate or high disease activity (DAS28-ESR ≥3.2) at week 24 of treatment with TCZ as a first-line bDMARD or whose DAS28-ESR score worsened after starting TCZ treatment. These patients could be followed for another 52 weeks or more after the subsequent switch to GLM treatment. For comparison, 19 patients treated with TNFi as a first-line bDMARD and inadequate response to TNFi (TNFi group) were included.

Results: The DAS28-ESR score at week 52 after the start of treatment with GLM improved significantly compared with baseline in the TCZ and TNFi groups. However, the TCZ group showed significantly better improvement. Patients in both groups had significantly improved treatment outcomes according to European League Against Rheumatism response criteria, but there was no statistically significant difference among them. The retention rate at week 52 after the start of treatment with GLM was significantly higher in the TCZ group than in the TNFi group (81% vs. 68%, respectively). In addition, no difference was found in the progression of bone destruction determined by the change in van der Heijde modified total Sharp scoring system scores between groups.

Conclusions: GLM was an effective therapeutic option for inadequate responders to TCZ.     

Prediction of DAS28-ESR remission at 6?months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX.     

Long-term efficacy of leflunomide on disease activity and inhibition of joint damage: retrospective comparison with methotrexate for Japanese rheumatoid arthritis patients

Abstract

We retrospectively compared treatment impact with leflunomide (LEF) or methotrexate (MTX) on retarding joint damage and clinical symptom including a 28-joint-count Disease Activity Score/erythrocyte sedimentation rate (DAS28-ESR) between two similar groups in patients with rheumatoid arthritis (RA) over an approximately 3-year treatment. One group included 29 patients treated with LEF alone (average dose 16.1 mg/day); the other group included 26 patients treated with MTX (average dose 7.4 mg/week) alone or combined with other disease-modifying antirheumatic drugs. At baseline, mean disease duration was 7.1 and 6.9 years, and mean DAS28-ESR was 5.79 and 5.69, respectively. The average DAS28-ESR improvement of 1.750 (from 5.79 to 4.04) in the LEF-treated group was significantly greater than the effect of 1.007 (from 5.69 to 4.68) seen in the MTX group (P = 0.0455), with the same results being observed on European League Against Rheumatism (EULAR) response criteria. Annual changes observed in Larsen score in total joints were 0.030 in the LEF group and 0.085 in the MTX group: LEF retards joint damage significantly better than MTX (P = 0.003). This inhibitory effect was better in small joints (P = 0.004) than in middle and large joints (P = 0.075). A negative correlation was noticed between improved DAS28-ESR and the progression of joint damage in the LEF group (r = ?0.7068, P < 0.0001), whereas there was no correlation in the MTX group (r = ?0.0311, P = 0.882). In daily clinical practice, LEF showed significant clinical and radiological improvement compared with the standard MTX regimen in Japan.     

Identification of clinical parameters associated with serum oxidative stress in patients with rheumatoid arthritis

Abstract

Objectives. Reactive oxygen species (ROS) are considered to be involved in the pathobiology of rheumatoid arthritis (RA); however, their association with disease activity has not been elucidated. In this study, we measured reactive oxygen metabolites (ROM) in patients with RA using a new Free Radical Analytical System and determined clinical parameters associated with ROM.

Methods. One hundred and fifty-two patients with RA and 80 patients with diabetes mellitus (DM) were included in this observational study. To measure ROM, the d-ROM test was performed on blood samples drawn from all subjects. The correlation between ROM and biomarkers, disease activity, doses of methotrexate (MTX), and prednisolone (PSL) were investigated.

Results. There were significant, positive correlations between ROM and CRP, matrix metalloproteinase 3 (MMP3), Disease Activity Score 28–erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). Multiple regression analysis revealed that CRP and DAS28-ESR were correlated with ROM.

Conclusions. The serum level of ROM was associated with CRP and DAS28-ESR, suggesting that ROM, in conjunction with CRP and MMP3, may be able to be used as a new biological disease marker to evaluate the disease activity of RA.     

The efficacy of abatacept in Japanese patients with rheumatoid arthritis: 104 weeks radiographic and clinical results in clinical practice

Objective: We aimed to assess the efficacy of abatacept in Japanese patients with rheumatoid arthritis (RA) in clinical practice.

Methods: We examined 92 patients who received abatacept for 104 weeks. Analysis of radiographic efficacy was conducted using van der Heijde-modified total Sharp score (mTSS). Disease activity score was assessed using disease activity score in 28 joints (DAS28) and simplified disease activity index (SDAI) by last observation carried forward.

Results: The change in mTSS was 0.61 at 52 weeks and 0.27 at 52–104 weeks. Structural remission occurred in 64.9% at 52 weeks and 76.6% at 104 weeks. The significant risk factors for joint damage progression at 52 weeks were prednisolone use, baseline C-reactive protein level (CRP), and erythrocyte sedimentation rate (ESR), as well as average DAS28-CRP and DAS28-ESR scores, SDAI, CRP, ESR, and matrix metalloproteinase-3 (MMP-3) levels. The clinical remission rates were 47.8% by DAS28-CRP, 39.1% by DAS28-ESR, and 30.4% by SDAI at 52 weeks, were 59.8% by DAS28-CRP, 48.9% by DAS28-ESR, and 43.5% by SDAI at 104 weeks.

Conclusion: This study suggested efficacy of abatacept treatment in Japanese patient with RA for 104 weeks in daily clinical practice. Abatacept lead to suppress joint destruction for 104 weeks.     

Long-term Use of Golimumab in Daily Practice for Patients with Rheumatoid Arthritis

Objective To evaluate the effectiveness and drug retention rate of golimumab (GLM) for long-term use in daily practice for patients with rheumatoid arthritis (RA). Methods Patients with RA who started GLM therapy with a minimum follow-up period of 52 weeks were included. The patients were divided into a biologic-naïve group and switch group. The disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (DAS28-ESR), grip power, and Japanese version of the health assessment questionnaire (J-HAQ) score were assessed. In addition, the treatment continuation rate was evaluated at the final follow-up. Patients Sixty-five patients [58 women and 7 men; median (range) age, 69 (61-74) years; median (range) disease duration, 9 (5-16) years] were included. Twenty-eight patients were biologic-naïve (naïve group), and 37 were switched to biologics (switch group). Results The median (range) follow-up period was 134 (58-162) weeks. The DAS28-ESR improved from a median (range) of 4.31 (3.52-5.25) to 2.65 (2.28-3.77) in the naïve group and from 4.27 (3.19-4.89) to 2.89 (2.49-3.88) in the switch group. The grip power improved in both groups (p<0.01); however, the J-HAQ score showed no marked improvement in either group. The continuation rates were 22/28 (78.6%) in the naïve group, and 26/37 (70.3%) in the switch group at the final follow-up. Conclusion We herein report for the first time that the long-term use of GLM improves the grip power. Improving the grip power may help prevent sarcopenia and frailty in the future. Given the efficacy and high continuation rate, we suggest that GLM would be a well-tolerated treatment option for RA.     

Fractures lead to worsening of disease activity in rheumatoid arthritis

Objectives: The cause of rheumatoid arthritis (RA) flares is multifactorial and not well understood. No reports of fractures influencing disease activity in patients with RA have been published. The purpose of this study was to determine whether fractures influence disease activity in patients with RA.

Methods: Hospital records of 470 patients with RA between 2011 and 2014 were analyzed. We first examined the incidence of flare using multiple regression analysis. Secondly, we examined the incidence of flare using DAS28-ESR, DAS28-CRP, and drug changes before bone fracture until bone union in the fracture cases.

Results: Multiple linear regression analysis showed that female sex (p?<?0.001), bottom DAS28-ESR (p?<?0.001), and fracture (p?=?0.041) were independent factor for DAS28-ESR at the last observation period, and sex (p?=?0.040), bottom DAS28-CRP (p?<?0.001), and fracture (p?=?0.019) were independent factor for DAS28-CRP at the last observation period. The average DAS28-ESR value was significantly increased from 3.19 (prefracture) to 3.58 (bone union). The average DAS28-CRP value was also significantly increased from 2.45 (prefracture) to 2.79 (bone union).

Conclusions: We have demonstrated that fractures influence disease activity in patients with RA. Larger numbers of fracture cases are required to confirm the present observations; however, the prevention of fracture is clearly required in patients with RA.     

Time lag between the initiation of adalimumab after methotrexate correlates with the efficacy of adalimumab in rheumatoid arthritis patients

Objectives: To evaluate the efficacy and safety of adalimumab (ADA) and methotrexate (MTX) in patients with rheumatoid arthritis (RA) and investigate critical factors associated with efficacy.

Methods: In this retrospective cohort study, patients received ADA at a single facility. Clinical outcome was retrospectively evaluated using the Disease Activity Score in 28 joints with Erythrocyte Sedimentation Rate (DAS28-ESR).

Results: Of the 122 patients undergoing treatment with ADA between July 2008 and April 2014, DAS28-ESR data after 6 months of treatment were available for 103 and 87 (84.5%) were treated with a combination of ADA and MTX. For combination therapy, time lag between MTX and the initiation of ADA significantly correlated with efficacy of ADA at 6 months, as well as prior use of biologics, but not disease duration.

Conclusions: Clinical outcomes were correlated with the time lag between MTX and the initiation of ADA, not disease duration. Early initiation of ADA after MTX might improve clinical outcomes.     

A randomized,double-blind,parallel-group,phase III study of shortening the dosing interval of subcutaneous tocilizumab monotherapy in patients with rheumatoid arthritis and an inadequate response to subcutaneous tocilizumab every other week: Results of the 12-week double-blind period

Objective: To determine the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) monotherapy every week (qw) versus every other week (q2w) in patients with rheumatoid arthritis who had an inadequate response to TCZ-SC q2w.

Methods: Adult patients in Japan with inadequate response to TCZ-SC q2w were randomized to either TCZ-SC 162?mg qw monotherapy or TCZ-SC 162?mg q2w monotherapy for 12 weeks (double-blind). The primary endpoint was the change from baseline in adjusted Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) at week 12. Efficacy, safety and pharmacokinetics were assessed.

Results: TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12. The difference in the change in DAS28-ESR between TCZ-SC qw and q2w was ?1.21 (95%CI:??2.13,??0.30, p?=?.0108). A higher proportion of patients receiving TCZ-SC qw achieved DAS28-ESR remission/low disease activity than TCZ-SC q2w. Adverse events were 71.4% and 66.7% for TCZ-SC qw and q2w, respectively; infection was the most common event with one fatal case with TCZ-SC qw.

Conclusions: In patients with inadequate response to TCZ-SC q2w, shortening the dosing interval to qw improved efficacy with acceptable tolerability. Occurrence of infection for both TCZ q2w and qw is important and needs careful attention.