Efficacy and safety of abatacept in routine care of patients with rheumatoid arthritis: Orencia® as Biological Intensive Treatment for RA (ORBIT) study

Abstract

Objective. To investigate the efficacy and safety of abatacept for treating patients with rheumatoid arthritis (RA) in routine clinical practice.

Methods. We performed a retrospective study of 137 RA patients who were treated with abatacept for 24 weeks between October 2010 and June 2011 at four rheumatology centers in Japan. Outcomes were compared between biologic-naïve and biologic-experienced patients. Disease activity was assessed using the Simplified Disease Activity Index (SDAI) and the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR).

Results. The retention rate of abatacept at 24 weeks was 79.6%. SDAI (from 24.6 ± 12.5 to 12.9 ± 11.6) and DAS28-ESR (from 5.2 ± 1.4 to 3.9 ± 1.4) decreased significantly from baseline to Week 24 (both P < 0.001). Remission/low disease activity were achieved in 2.2%/11.2% (SDAI) and in 5.3%/2.3% (DAS28-ESR). The change in SDAI and the remission/low disease activity rates at Week 24 was greater in biologic-naïve patients than in biologic-experienced patients. Structural remission (van der Heijde-modified total Sharp score ≤ 0.5) was achieved by 63.4% of patients.

Conclusions. The present results confirm that abatacept is effective in routine clinical practice and support its use as the first-line biologic agent in patients.     

Effectiveness of abatacept for patients with Sjögren’s syndrome associated with rheumatoid arthritis. An open label,multicenter, one-year,prospective study: ROSE (Rheumatoid Arthritis with Orencia Trial toward Sjögren’s syndrome Endocrinopathy) trial

Objective: To clarify the efficacy and safety of abatacept for secondary Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA).

Methods: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon’s test and Schirmer’s test. Adverse events and adherence rate during the study period were also analyzed.

Results: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6?±?11.2 (±SD) at baseline to 10.0?±?10.5 at 52 weeks (p?<?0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon’s test increased significantly from 2136?±?1809 (0 week) to 2397?±?1878 (24 weeks) mg/2?min (n?=?34, p?<?0.05). Saliva volume increased significantly from 2945?±?2090 (0 week) to 3419?±?2121 (24 weeks) mg/2?min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p?<?0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer’s test increased significantly from 4.2?±?4.8 (0 week) to 6.4?±?7.8 (24 weeks) mm/5?min (n?=?30, p?<?0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections.

Conclusion: Abatacept seems to be effective for both RA and SS related manifestations.     

Clinical outcome in patients with rheumatoid arthritis switched to tocilizumab after etanercept or infliximab failure

The present study retrospectively assessed the efficacy of tocilizumab in patients with rheumatoid arthritis (RA) who failed to respond to treatment with etanercept or infliximab. A retrospective study of 33 RA patients who did not respond to etanercept or infliximab was conducted. Responses of subjects switching from etanercept to tocilizumab (n?=?17) were compared with those switching from infliximab to tocilizumab (n?=?16). Treatment with disease-modifying antirheumatic drugs before the switch, especially methotrexate (MTX), was maintained. Disease activity was assessed by the Disease Activity Score 28-C Reactive Protein (DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Patients who switched from etanercept were significantly less likely to have used MTX and were significantly older than patients who switched from infliximab. In both groups, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values at 24 weeks with no significant differences between groups. However, at week 52, DAS28-CRP, SDAI, and CDAI values in the group switched from etanercept were significantly worse than those in the group switched from infliximab. All patients switched from infliximab were using MTX. In the evaluation between patients who switched from etanercept monotherapy, etanercept plus MTX, and infliximab plus MTX, a significant improvement from baseline was seen in DAS28-CRP, SDAI, and CDAI for all patients at 24 weeks with no significant differences between groups. Disease activity was maintained at 52 weeks in the group that switched from etanercept plus MTX and infliximab plus MTX. However, the efficacy of tocilizumab was decreased in the group that switched from etanercept monotherapy. Switching from etanercept plus MTX or from infliximab plus MTX to tocilizumab plus MTX improved response to therapy, but switching from etanercept monotherapy to tocilizumab monotherapy did not improve response to therapy.     

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.     

Efficacy and safety of abatacept for patients with Sjögren's syndrome associated with rheumatoid arthritis: Rheumatoid Arthritis with Orencia Trial toward Sjögren's syndrome Endocrinopathy (ROSE) trial—an open-label,one-year,prospective study—Interim analysis of 32 patients for 24 weeks

Abstract

Objective. To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA).

Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed.

Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections.

Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.     

托珠单抗联合改善病情抗风湿药治疗类风湿关节炎的多中心、随机、双盲、安慰剂对照临床研究

  目的 评价托珠单抗联合改善病情抗风湿药（DMARDs）治疗DMARDs疗效不佳的活动性中重度类风湿关节炎（RA）患者的有效性与安全性。方法 随机、双盲、安慰剂对照、多中心临床试验。DMARDs疗效不佳的中重度活动性RA患者按2∶1 的比例随机分入托珠单抗组(托珠单抗+DMARDs) 或安慰剂组(安慰剂+DMARDs),每4 周静脉滴注1次托珠单抗8 mg/kg,同时继续应用稳定剂量的DMARDs。完成双盲期的患者可以选择进入为期24周的开放期,接受每4周静脉滴注1次托珠单抗8 mg/kg。主要观察指标：第24周时达到美国风湿病学会（ACR）制定的RA疗效缓解20%（ACR20）、RA疗效缓解50%（ACR50）、RA疗效缓解70%（ACR70）的受试者比例;达到28个关节疾病活动指数（DAS）≤3.2、DAS28<2.6的受试者比例。结果 （1）托珠单抗组139例、安慰剂组69例患者完成了24周的双盲期临床观察,达到ACR20、ACR50和ACR70的受试者比例托珠单抗组（69.8%、38.8%、12.9%）显著高于安慰剂组（24.6%、10.1%、2.9%,P<0.05)。托珠单抗组患者红细胞沉降率、C反应蛋白、血红蛋白、DAS28≤3.2及DAS28<2.6的受试者比例的改善优于安慰剂组。托珠单抗组患者治疗后Ⅰ型胶原羧基端吡啶并啉交联肽、ⅡA型前胶原氨基端前肽、基质金属蛋白酶-3水平下降。（2）48周开放期共有202例RA患者接受了托珠单抗治疗,达到ACR20、ACR50、ACR70的受试者比例分别为81.2%、60.4%、36.6%。DAS28降至2.760±1.402,50.5%的患者达到DAS28<2.6。（3）托珠单抗组发生59例（42.4%）不良事件,高于安慰剂组（27.9%）。严重不良事件发生率托珠单抗组为0.7%,安慰剂组为5.9%。最常见的不良事件为感染,绝大多数为轻中度。托珠单抗组患者出现丙氨酸转氨酶和天冬氨酸转氨酶显著升高;总胆固醇、低密度脂蛋白、高密度脂蛋白和甘油三酯水平升高,但未观察到心血管事件的增加。治疗48周时未出现新的不良事件。结论托珠单抗联合DMARDs治疗DMARDs疗效不佳的中重度活动性RA患者有显著临床疗效,患者安全性与耐受性良好。        

Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

A retrospective study of 39 rheumatoid arthritis (RA) patients with an inadequate response to infliximab was conducted. The responses of subjects switching from infliximab to tocilizumab (n = 23) were compared to those of subjects switching to etanercept (n = 16). Disease activity was assessed by the Disease Activity Score 28-CRP ([C-reactive protein] DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Twenty-two patients completed 48 weeks of tocilizumab treatment, and 15 patients completed 48 weeks of etanercept treatment. In both treatment groups, 1 patient each discontinued treatment because of lack of efficacy. No serious adverse events occurred during the study, and no patients in either group withdrew due to adverse events. At week 48, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values after switching to either tocilizumab or etanercept, and there was no significant difference in efficacy, as measured by the DAS28-CRP, SDAI, and CDAI, between the two treatment groups (p = 0.12, 0.76, and 0.86, respectively). These results suggest that safety and tolerability were similar for both treatments. A switch from infliximab to either tocilizumab or etanercept in patients with RA who have not responded to infliximab is a feasible, well-tolerated treatment option.     

MRI assessment of erosion repair in patients with long-standing rheumatoid arthritis receiving double-filtration plasmapheresis in addition to leflunomide and methotrexate: a randomized controlled trial

The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of >?3 years’ duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods. The primary endpoint was the change in MRI bone erosion over 12 months. Patients treated with DFPP in addition to DMARDs demonstrated significantly greater decrease in MRI erosion score compared with those treated with DMARDs, being 11.3?±?9.6 at month 12, compared with 16.9?±?8.3 in patients with DMARDs (P?<?0.001), and compared with 14.4?±?9.6 at baseline (P?<?0.001). 84.2% of patients treated with DFPP in addition to DMARDs demonstrated a decrease in MRI erosion score. Synovitis and bone edema improved significantly with DFPP in addition to DMARDs compared with DMARDs at months 6 and 12. (1.05?±?1.7 and 2.0?±?3.9 compared with 8.0?±?1.4 and 12.6?±?7.9 at month 12). Patients without synovitis and bone edema reached in 55.3% among patients with DFPP in addition to DMARDs. This study demonstrated that DFPP combination therapy significantly decreased bone erosion and received the primary goal of repair of erosions through abrogating MRI inflammation (synovitis and bone edema) in long-standing RA patients with high disease activity. The findings suggest that addition of DFPP is associated with repair of erosions and further suppression of inflammation.     

Chronological changes in baseline disease activity of patients with rheumatoid arthritis who received biologic DMARDs between 2003 and 2012

Abstract

Background/Purpose. The use of biologic disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA) has been increasing since 2003. In this study, we evaluated changes in the characteristics of patients receiving biologic DMARDs daily, in Japan.

Methods. The characteristics of all RA patients who received any biologic DMARD at the Institute of Rheumatology, Tokyo Women's Medical University, within 1 year after its approval in Japan, were retrospectively evaluated. The periods of patient enrollment for each biologic agent were: infliximab (IFX), 2003–2004; etanercept (ETN), 2005–2006; tocilizumab (TCZ), 2008–2009; adalimumab (ADA), 2008–2009; abatacept (ABT), 2010–2011; and golimumab (GLM), 2011–2012. We retrospectively collected individual patient characteristics, concomitant medication usage, and disease activity assessed by disease activity score 28 (DAS28) at the time of administration, from the medical records. The retention rate for each agent at 6 months after treatment initiation was also assessed.

Results. The numbers of patients who received each biologic DMARD at our institute within 1 year after its approval were: IFX, 49; ETN, 50; TCZ, 62; ADA, 52; ABT, 40; and GLM, 77. From 2003 to 2012, the proportion of patients with prior use of any biologic DMARD increased, as did concomitant use and dose of methotrexate (MTX); however, corticosteroid use and doses decreased. DAS28, at the time of treatment initiation, gradually decreased. At the time of IFX administration, 75% and 25% of patients had high and moderate disease activity respectively, compared to 25% and 58% respectively, of patients who received GLM. No significant difference was observed in the retention rate of biologic DMARDs at 6 months (range, 75.0% to 89.6%).

Conclusion. Baseline disease activity of RA patients who received biologic DMARDs between 2003 and 2012 has changed from high to moderate in daily practice in Japan.     

Very early treatment with infliximab in addition to methotrexate in early,poor‐prognosis rheumatoid arthritis reduces magnetic resonance imaging evidence of synovitis and damage,with sustained benefit after infliximab withdrawal: Results from a twelve‐month randomized,double‐blind,placebo‐controlled trial

Objective

Anti–tumor necrosis factor α agents are among the most effective therapies for rheumatoid arthritis (RA). However, their optimal use is yet to be determined. This 12‐month double‐blind study attempted remission induction using standard therapy with or without infliximab in patients with early, poor‐prognosis RA. The primary end point was synovitis (measured by magnetic resonance imaging [MRI]). Clinical observations continued to 24 months.

Methods

All patients had fewer than 12 months of symptoms. Assessments included full metrologic evaluation, laboratory tests, radiographs, functional evaluation using the Health Assessment Questionnaire (HAQ), and quality of life measurement using the RA Quality of Life (RAQoL) questionnaire. MRI was performed at 0, 4, 14, and 54 weeks; MR images were scored blindly. Patients received methotrexate (MTX) and were randomized to receive either infliximab or placebo for 12 months.

Results

Twenty patients were recruited (mean age 52 years, mean symptom duration 6 months, mean C‐reactive protein level 42 mg/liter, and 65% rheumatoid factor positive). At 1 year, all MRI scores were significantly better, with no new erosions in the infliximab plus MTX group; a greater percentage of infliximab plus MTX–treated patients fulfilled the American College of Rheumatology (ACR) 50% and 70% improvement criteria (78% versus 40% in the placebo plus MTX group and 67% versus 30%, respectively) and had a greater functional benefit (P < 0.05 for all comparisons). Importantly, at 1 year after stopping induction therapy, response was sustained in 70% of the patients in the infliximab plus MTX group, with a median Disease Activity Score in 28 joints (DAS28) of 2.05 (remission range). At 2 years, there were no significant between‐group differences in the DAS28, ACR response, or radiographic scores, but differences in the HAQ and RAQoL scores were maintained (P < 0.05).

Conclusion

Remission induction with infliximab plus MTX provided a significant reduction in MRI evidence of synovitis and erosions at 1 year. At 2 years, functional and quality of life benefits were sustained, despite withdrawal of infliximab therapy. These data may have significant implications for the optimal use of expensive biologic therapies.

     

Retreatment efficacy and safety of tocilizumab in patients with rheumatoid arthritis in recurrence (RESTORE) study

Abstract

Objectives To evaluate the safety and efficacy of retreatment with tocilizumab (TCZ) in patients who had participated in the DREAM study (Drug free remission/low disease activity after cessation of tocilizumab [Actemar] monotherapy study) and had experienced loss of efficacy.

Methods Patients were retreated with TCZ or other disease modifying antirheumatic drugs (DMARDs). Disease activity was measured using the 28-joint disease activity score (DAS28) for 12 weeks.

Results A total of 164 eligible patients, including 161 who experienced loss of efficacy within 52 weeks of the DREAM study, resumed treatment: 157 with TCZ and 7 with DMARDs and/or infliximab. Of TCZ-treated patients, 88.5 % (139 patients) achieved DAS28 <2.6 within 12 weeks, whereas among patients treated with DMARDs and/or infliximab only 14.3 % (1 patient) achieved DAS28 <2.6. Adverse events were observed in 70 TCZ-treated patients (44.0 %), but no serious infusion reactions were observed.

Conclusions Retreatment with TCZ was well-tolerated and effective in patients who had responded to the preceding TCZ monotherapy but had experienced loss of efficacy after cessation of TCZ.     

Abatacept inhibits radiographic progression in patients with rheumatoid arthritis: a retrospective analysis of 6 months of abatacept treatment in routine clinical practice. The ALTAIR study

Abstract

Objectives Our objectives in this study were to determine the inhibitory effects of abatacept on joint damage and its clinical efficacy and safety in patients with rheumatoid arthritis (RA).

Methods Fifty Japanese patients with RA were treated with abatacept for 24 weeks in routine clinical practice.

Results At week 24, 20 % of patients achieved clinical remission [Simplified Disease Activity Index (SDAI) ≤3.3], whereas 50 % were in remission or had a low disease activity. Structural remission [progression of modified total Sharp score (ΔmTSS) ≤0.5] was achieved in 76 % of patients. The ΔmTSS decreased significantly from 7.1 ± 7.3 at baseline to 1.8 ± 5.7 at week 24. C-reactive protein (CRP) was the only independent prognostic factor for joint damage progression at week 24, whereas SDAI and matrix metalloproteinase-3 levels were not. A very high proportion of patients with CRP levels <1.5 mg/dl (88 %) achieved structural remission. In terms of safety, the retention rate for all patients was favorable (80 %), and stomatitis was the only adverse event observed. No patient withdrew from the study because of infections.

Conclusions Abatacept has favorable clinical and structural effects, inhibits radiographic progression, and has a good safety profile in routine clinical practice.     

The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis: Preliminarily data from single center-based observational study for 24 weeks

Baricitinib is a Janus kinase (JAK) inhibitor that selectively blocks against JAK1 and JAK2 signaling. This study aimed to determine the effect of baricitinib on disease activity based on musculoskeletal ultrasound in patients with rheumatoid arthritis (RA).A total of 20 patients with RA receiving baricitinib for 24 weeks were assessed. Ultrasound scores of gray scale and power Doppler synovitis, joint effusion, and bone erosion in each patient were assessed between baseline and 24 weeks for 27 affected joints. Disease activity in RA was evaluated using the disease activity score for 28-joint count with erythrocyte sediment rate (DAS28-ESR), simplified disease activity index (SDAI), and clinical disease activity index (CDAI).Treatment with baricitinib for 12 weeks and 24 weeks significantly decreased disease activity composites such as DAS28-ESR, SDAI, and CDAI (P < .001 for all). Treatment with baricitinib for 24 weeks improved ultrasound-detected gray-scale and power Doppler synovitis and joint effusion compared to baseline (P = .002, P = .030, and P = .002, respectively). Bone erosion scores were not different between baseline and 24 weeks (P = .317). There were no differences in ultrasound abnormalities for improvement based on DAS28-ESR. Changes in power Doppler score were significantly associated with changes in DAS28-ESR (β = 0.590, P = .044), but not SDAI and CDAI.This study demonstrates that baricitinib treatment has a favorable effect on ultrasound-detected abnormalities including synovitis and bone erosion in patients with RA.     

Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infliximab: clinical and magnetic resonance imaging evaluation

The objectives of this study was to assess, using clinical and magnetic resonance imaging (MRI) criteria, the efficacy of combination infliximab therapy in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX) treatment and to ascertain whether the changes in MRI parameters correlate with the clinical response. Four infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and 14 were added to a stable background dose of MTX in 19 patients with active disease. Clinical parameters were assessed before each infusion and at week 14. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at baseline and week 14. Synovitis severity, volume of synovitis, and synovial perfusion indices were evaluated. Significant improvement in all clinical disease activity parameters was seen at week 14 with reduction in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28. Sixty-eight percent of patients achieved ACR20. MRI disease activity parameters also significantly decreased after treatment with reduction in grading of synovitis, volume of active synovitis, and perfusion enhancement slope. Significant positive correlations were seen between the baseline volume of synovitis and the pain score (r=0.65), patient global score (r=0.68), and health assessment questionnaire (HAQ) score (r=0.46). In conclusion, addition of infliximab to methotrexate rapidly reduces inflammation in longstanding patients with RA. Assessment of enhancing synovial volume and perfusion indices on serial MRI examination was helpful in documenting the effect of treatment over this short period.     

Development and evaluation of a novel ultrasound score for large joints in rheumatoid arthritis: one year of experience in daily clinical practice

Objective

To introduce and evaluate a new standardized ultrasound (US) score developed for large joints in patients with rheumatoid arthritis (RA).

Methods

A US score was designed to determine the degree of inflammation in the shoulder, the elbow, the hip, and the knee joint in patients with RA (Sonography of Large Joints in Rheumatology [SOLAR] score). Synovitis and synovial vascularity were scored semiquantitatively (grade 0–3) by gray‐scale US (GSUS) and power Doppler US (PDUS). Patients with RA were examined at baseline and 3, 6, and 12 months after initiation of local or systemic therapy (disease‐modifying antirheumatic drugs [DMARDs]/biologic agents). Erythrocyte sedimentation rate, anti–cyclic citrullinated peptide antibodies, and the clinical Disease Activity Score in 28 joints (DAS28) were determined.

Results

A cohort of 199 patients were analyzed and followed up over 12 months. At baseline, before modification of the therapy, patients received either DMARDs (n = 131), DMARDs plus biologic agents (n = 46), biologic monotherapy (n = 8), or no DMARD therapy (n = 14). At baseline, the mean DAS28 score was 4.6 and decreased to 3.2 after 1 year of therapy (P < 0.001). All US scores demonstrated a statistically significant improvement except for the PDUS scores for the shoulder and the hip. In detail, the mean synovitis GSUS score for the knee decreased from 5.2 at baseline to 2.2 after 12 months of followup. The mean GSUS score for the shoulder fell from 2.6 to 1.6, for the elbow fell from 5.2 to 2.6, and for the hip fell from 2.2 to 0.4 (P < 0.05 for each).

Conclusion

The SOLAR score is a feasible tool for the qualitative and quantitative evaluation of large joint involvement in patients with RA using US.     

Treatment discontinuation in patients with very early rheumatoid arthritis in sustained simplified disease activity index remission after synthetic disease-modifying anti-rheumatic drug administration

Abstract

We aimed to identify whether drug-free remission could be achieved in patients with very early rheumatoid arthritis (RA) with poor prognosis factors by treatment with synthetic disease-modifying antirheumatic drugs (DMARDs). Thirteen patients with very early RA, whose disease was considered to have highly erosive potential, were included. Magnetic resonance imaging (MRI)-proven bone edema and autoantibodies were determined in these patients. A treat-to-target strategy initiated with synthetic DMARDs was employed for 12 months. If the patients achieved simplified disease activity index (SDAI) remission along with a reduction of the RA MRI scoring bone edema score to <33% as compared with baseline at 12 months, DMARD treatment was stopped and the clinical status was further observed for the following 12 months. Synthetic DMARDs were stopped at 12 months in 5 patients. One of the 5 was lost to follow-up because of sustaining an injury that required orthopedic surgery. Three of the remaining 4 patients showed continued SDAI remission that was DMARD-free without any evidence of radiographic progression for the following 12 months. Although this was a small clinical trial, we have shown–for the first time–that true remission of very early RA with poor prognosis factors can be achieved by treatment with synthetic DMARDs.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

Abstract

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

Biologic Agents Reduce Cardiovascular Events in Rheumatoid Arthritis Not Responsive to Tumour Necrosis Factor Inhibitors: A National Cohort Study

BackgroundTumour necrosis factor inhibitors (TNFis) improve joints outcomes and reduce cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). However, 20%-45% of RA patients are TNFi poor responders and have a significantly higher risk of CV events. In these TNFi nonresponders, the use of second-line biologic agents to improve synovial outcomes is supported by clinical trials and real-world experience. However, it remains unknown what kind of immune-mediated agent has the best CV prevention effect in this high-risk population.MethodsA nationwide RA cohort obtained from Taiwan’s National Health Insurance claims database was constructed. RA patients first treated with TNFis who then received either rituximab, tocilizumab, or abatacept were enrolled and followed for 2 years.ResultsA total of 89,973 RA patients were screened and 1,584 patients ultimately included. The incidences of major adverse cardiac events (MACE) at 2 years in the rituximab, tocilizumab, and abatacept groups were 7.17%, 2.75% and 2.38%, respectively. Multivariate adjusted Cox analysis showed that tocilizumab had significantly lower risk than rituximab in myocardial infarction (hazard ratio [HR] 0.12, 95% confidence interval [CI] 0.02-0.56; P = 0.008), and MACE (HR 0.41, 95% CI 0.23-0.72; P = 0.002). In addition, abatacept also had significant lower adjusted risk than rituximab in stroke (HR 0.18, 95% CI 0.05-0.64; P = 0.008), heart failure (HR 0.20, 95% CI 0.05-0.83; P = 0.027), and MACE (HR 0.25, 95% CI 0.11-0.55; P < 0.001) in multivariate analysis.ConclusionsTNFi-nonresponder patients with RA who received second-line tocilizumab or abatacept had more benefit on CV events prevention compared with those who received rituximab.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

No erosive progression revealed by MRI in rheumatoid arthritis patients treated with etanercept,even in patients with persistent MRI and clinical signs of joint inflammation

The aim of this study is to investigate the course of magnetic resonance imaging (MRI) signs of inflammatory and destructive changes in rheumatoid arthritis (RA) wrist and metacarpophalangeal (MCP) joints during etanercept treatment. MRI of the non-dominant wrist and second to fifth MCP joints was performed in five clinical active RA patients before and 4 and 16 weeks after initiation of etanercept treatment. MRI was evaluated according to the EULAR–OMERACT RA MRI reference image atlas. The median 28-joint count disease activity score (DAS28; erythrocyte sedimentation rate based) was 5.6 (range 5.0–6.8) at baseline and 3.5 (1.5–4.1) at week 16 (decreased in all patients compared to baseline, Wilcoxon–Pratt, p < 0.05). The median MRI synovitis score was 18 (14–21), 18 (10–20) and 16 (10–20) at baseline, week 4 and 16, respectively (decreased in all patients compared to baseline, Wilcoxon–Pratt, p < 0.05), while corresponding MRI bone oedema scores were 4 (0–13), 3 (0–9) and 1 (0–3; NS). The median MRI bone erosion score was 27 (11–111; NS) at all time points. Four patients had identical total bone erosion scores at baseline and week 16, whereas one patient showed a reduced score. In conclusion, one patient showed erosive regression, while no patient showed erosive progression on MRI during 16 weeks of etanercept therapy; even though clinical and MRI signs of joint inflammation remained. This small study supports that erosive progression judged by MRI is minimal in RA patients treated with etanercept, even in joints with persistent inflammation.