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.     

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.     

Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission

Objective: The aim of this study was to identify the effect of mucosal healing (MH) on clinical relapse in patients with ulcerative colitis (UC) who are in clinical remission, with special reference to Mayo endoscopic subscore 0.

Methods: Between November 2005 and December 2013, medical records from a total of 215 patients with UC who underwent colonoscopic examination at the time of clinical remission were retrospectively reviewed. Endoscopic MH was defined as a ‘0 point’ of Mayo endoscopic subscore (Mayo 0). Patients were categorized into two groups according to Mayo endoscopic subscore and then analyzed.

Results: The baseline characteristics of both groups (MH vs. no-MH), including age at diagnosis, gender, and initial clinical and colonoscopic findings, were not significantly different. The median follow-up duration was 80 (12–118) months. Factors predictive of longer clinical remission duration were age ≥30 years at diagnosis (≥30 years vs. <30 years; hazard ratio [HR] 3.16, 95% CI 1.88–5.30, p?p?=?0.015), and presence of MH at clinical remission (HR 1.95, 95% CI 1.15–3.32, p?=?0.014). With a Cox regression model, patients with MH at clinical remission were more likely to have longer duration of clinical remission than patients without MH.

Conclusion: The achievement of MH, Mayo 0 in particular, in patients with UC who are in clinical remission is important in predicting a favorable disease course prognosis.     

The efficacy and safety of additional administration of tacrolimus in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab

Objectives: Tocilizumab (TCZ) shows good retention in patients with rheumatoid arthritis (RA), but no previous reports demonstrated hopeful treatment options against inadequate response to TCZ. Tacrolimus (TAC) has proved to show efficacy against inadequate response to tumor necrosis factor alpha inhibitors, yet its add-on effects on TCZ remain unknown.

Methods: Twenty patients with RA (17 women, age 58.6 years, disease duration 12.1 years, prior TCZ duration 2.6 years, 18 intravenous [8?mg/kg/month] and 2 subcutaneous [324?mg/month] TCZ treatments, methotrexate 6.1?mg/week [70.0%]) who showed an inadequate response to TCZ (clinical disease activity index [CDAI]?≥?5.8, 18 secondary non-responders) were additionally treated with TAC (1.1?mg/day), and enrolled in this 24-week, prospective study.

Results: Seventeen patients (85.0%) continued the treatment for 24 weeks. Statistically significant decreases in outcome measures were as follows: disease activity score based on 28 joints with C-reactive protein (DAS28-CRP) from 3.3 at baseline to 2.1 at week 24 (p?p?p?Conclusions: Adding low-dose TAC to inadequate responders to TCZ may be a promising complementary treatment option.     

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis

Objectives: To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission.

Methods: Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 – erythrocyte sedimentation rate [ESR]?≤?2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits.

Results: Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five.

Conclusion: A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.     

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.     

Body mass index is related with the presence of syndesmophyte in axial spondyloarthritis: Data from the Korean College of Rheumatology BIOlogics (KOBIO) registry

Objective: We investigated whether body mass index (BMI) is associated with parameters of disease activity and clinical manifestations in axial spondyloarthritis (axSpA).

Methods: Demographic, clinical, and radiological features and disease activity indexes from 789 axSpA patients (619 males and 170 females) were obtained from the Korean College of Rheumatology BIOlogics (KOBIO) registry. BMI (kg/m²) was classified into normal (BMI <23.0), overweight (23.0?≤?BMI <25.0), and obese (BMI ≥25.0). Disease activity indexes included Bath ankylosing spondylitis disease activity index (BASDAI), erythrocyte sediment rate (ESR), C-reactive protein (CRP), and ankylosing spondylitis disease activity score (ASDAS).

Results: The mean BMI in patients with axSpA was 23.3?±?3.5. 50.2% of all patients were overweight or obese. Overweight/obese patients had more syndesmophyte and less peripheral arthritis than those in normal BMI patients (p?p?p?p?=?0.002)

Conclusions: Our results imply that increased BMI is significantly associated with the presence of syndesmophyte, but not with disease activity in axSpA.     

Noninvasive evaluation of gastric emptying and gastric wall thickness in SLE patients

Objective: The objective of this study is to evaluate the gastric emptying in patients with systemic lupus erythematosus (SLE) with gastrointestinal involvement using three-dimensional (3D) ultrasonography.

Methods: The gastric emptying times at 25% (T1), 50% (T2), and 75% (T3) of SLE patients with gastrointestinal involvement (n?=?40) and healthy controls (n?=?80) were evaluated and compared. In addition, the correlations among the gastric wall thickness, SLE disease activity index (SLEDAI), and upper gastrointestinal symptoms were calculated.

Results: The gastric wall thickness was correlated with the SLEDAI (r?=?0.928, p?<?0.001) and the upper gastrointestinal symptom index (r?=?0.848, p?<?0.001). The emptying times T1, T2, and T3 of the SLE patients were 17.08?±?2.65?min (mean?±?standard deviation), 39.85?±?6.54?min, and 83.58?±?7.12?min, respectively. For healthy controls, they were 19.65?±?5.39?min, 41.08?±?7.51?min, and 70.34?±?8.03?min. The T1 of the SLE patients was shorter (p?<?0.01), while the T3 was longer (p?<?0.001). Moreover, T3 in the SLE group had the best correlation with the upper gastrointestinal symptom index (r?=?0.553, p?<?0.001). T1 in the SLE group was anti-correlated with early satiety (r?=??0.366, p?<?0.05).

Conclusions: Combining the emptying times T1 and T3, as well as the gastric wall thickness, the SLEDAI and the upper gastrointestinal symptoms index can provide accurate clinical diagnosis of SLE with gastric involvement.     

Add-on iguratimod as a therapeutic strategy to achieve remission in patients with rheumatoid arthritis inadequately responding to biological DMARDs: A retrospective study

Objectives: In this study, iguratimod (IGU) was added to rheumatoid arthritis (RA) patients inadequately responding to 24-week or longer treatment with biological disease-modifying antirheumatic drug (bDMARDs), its effectiveness was assessed, and factors contributing to remission were evaluated.

Methods: RA patients who fulfilled the following criteria were included: (i) ≥?24-week of bDMARDs; (ii) 2.6?Results: DAS assessing 28 joints with ESR (DAS28-ESR) decreased significantly from 3.45?±?0.92 at baseline to 2.85?±?1.13 at 24 weeks (p?p?p =.002). Shorter duration of disease (p =.020) was related to ultrasound remission, in addition to a lower baseline DAS28-ESR (p?Conclusions: IGU add-on therapy can be a therapeutic strategy to achieve remission in RA patients inadequately responding to ≥24-week treatment with bDMARDs.     

Gastroesophageal reflux disease in patients with rheumatoid arthritis

Abstract

Objective. Patients with rheumatoid arthritis (RA) are frequently complicated with gastric mucosal injury; however, there are few reports investigating gastroesophageal reflux disease (GERD) among patients with RA. We investigated the frequency of GERD and the correlation between GERD and the clinical characteristics of RA including patient's global assessment (PGA).

Methods. Patients with RA were investigated for GERD using self-administered frequency scale for the symptoms of GERD (FSSG). The correlation between GERD and the clinical characteristics of RA was analyzed statistically.

Results. Two hundred and eleven patients in Japan were investigated. The prevalence of GERD among patients with RA (24.6%) was significantly higher than that in the Japanese population (11.5%) (p < 0.001). FSSG was positively correlated with modified health assessment questionnaire (mHAQ), PGA, evaluator's global assessment (EGA) (p < 0.001), disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (p < 0.05), DAS28-C-reactive protein (CRP), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) (p < 0.001). The patients with GERD showed significantly higher scores in mHAQ, PGA, EGA, tenderness joint count, DAS28-ESR, DAS28-CRP, SDAI and CDAI (p < 0.001). Furthermore, the patients with GERD showed lower remission rates based on DAS28-ESR (p < 0.05), DAS28-CRP, SDAI and CDAI (p < 0.001).

Conclusion. GERD complicated with RA increases PGA and the indices of disease activity. GERD symptoms analyzed using FSSG may be desirable to avoid the overestimation as part of the total management of patients with RA.     

Alpha beta double negative T cells in children with systemic lupus erythematosus: The relation to disease activity and characteristics

Objectives: We aimed to investigate alpha beta double negative (αβ DN) T-cell percentages in juvenile systemic lupus erythematosus (JSLE) and their relation to disease activity and organ involvement.

Methods: This prospective study was carried out over a period of 12 months and included 21 JSLE patients and 20 healthy matched controls. SLE disease activity index 2000 (SLEDAI-2K) scores were recorded in addition to αβ DN T-cell percentages measurement at enrollment and after remission.

Results: Enrolled patients (n?=?21) were females with age range 10–17 years. Patients were followed up for a duration ranging 5–9 months. αβ DN T-cell percentages were higher in cases during activity [median (IQR): 3.7 (3.0–5.7)] versus remission [median (IQR): 1.4 (1.2–1.8)] and during activity and remission versus healthy controls [median (IQR): 1.0 (0.5–1.4)]. αβ DN T-cell percentages correlated positively with SLEDAI-2K score (p?p?=?.002) and with the presence of neurological (p?=?.028) and hematological (p?=?.032) manifestations.

Conclusion: αβ DNT cells percentages are elevated in patients with JSLE and their percentages correlate with disease activity. Further studies are needed in conjunction with the proinflammatory cytokine profile, apoptotic assays and histological findings.     

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.     

The add-on effectiveness and safety of iguratimod in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab

Abstract

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX).

Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8?mg/kg/4 weeks] and 6 subcutaneous [162?mg/2 weeks] TCZ treatments, concomitant MTX 8.5?mg/week [35.5%], and prednisolone (PSL) 4.3?mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7?mg/day) and enrolled in this 24-week, multicenter, retrospective study.

Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p?<?.001); CDAI from 15.0 to 6.0 (p?<?.001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p?<?.05); and rheumatoid factor (RF) from 382.1 to 240.3?IU/mL (p?<?.001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks.

Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option.     

Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods,in patients undergoing allogeneic hematopoietic stem cell transplantation

ABSTRACT

Objectives: Whole blood-derived platelet concentrates can be obtained by the platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies have shown that BC-PCs display lower in vitro platelet activation, but scarce information exists regarding transfusion efficacy. We have performed a retrospective study assessing platelet transfusion in patients undergoing allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and after the implementation of BC-PCs.

Methods: We reviewed clinical records corresponding to 70 PRP-PCs and 86 BC-PCs prophylactic transfusions, which were performed to 55 AHCT patients. Transfusion efficacy was assessed by the 24-h post-transfusion corrected count increment (24-h CCI) and bleeding events. Clinical factors affecting transfusion outcome were also investigated.

Results: Clinical characteristics and the total number of platelet transfusions were similar among groups. Mean donor exposure was 5.8 and 5.0 in each single PRP-PCs and BC-PCs transfusion, respectively (p?<?0.01). The 24-h CCI was significantly higher in patients transfused with BC-PCs than in those receiving PRP-PCs (8.3[2.7–13.4] vs. 4.7[1.3–8.1]; p?<?0.01). Independent predictors of poor platelet transfusion response included diagnosis other than acute leukemia (HR 8.30; 95% CI 1.96–35.22; p?=?0.004), splenomegaly (HR 8.75; 95% CI 2.77–27.60; p?<?0.001), graft versus host disease prophylaxis different from cyclosporine A and methotrexate (HR 3.96; 95% CI 1.55–10.14; p?=?0.004) and PRP-PCs transfusion (HR 4.54; 95% CI 1.72–12.01; p?=?0.002). There were no differences between both groups regarding the bleeding events.

Conclusion: In the AHCT setting, we hypothesize that BC-PCs transfusion, when compared to PRP-PCs, results in higher CCI and reduced donor exposure, but provides no significant benefit regarding bleeding outcome.     

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease

Objective: The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province.

Methods: Data of 678 incident IBD patients (Crohn’s disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21–40 years, disease duration: 6, IQR: 2–9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26–50 years, duration: 7, IQR: 4–10 years).

Results: EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p?=?0.02) need for steroid (p ?p?=?0.02), while in UC, young age at onset (p?=?0.03), extensive disease (p?=?0.003), female gender (p?=?0.07), need for steroids (p?p?=?0.004) and need for IBD-related hospitalization (p?=?0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (p_CD?=?0.001, p_UC?=?0.04), disease location/extent (p_CD?=?0.02, p_UC?p_CD,UC?p_CD?p_UC?=?0.002) and hospitalization (p_CD?=?0.004, p_UC?p?=?0.002).

Conclusions: The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.     

Biomarker for nontuberculous mycobacterial pulmonary disease in patients with rheumatoid arthritis: Anti-glycopeptidolipid core antigen immunoglobulin A antibodies

Objective: Nontuberculous mycobacterial (NTM) pulmonary disease is occasionally associated with rheumatoid arthritis (RA), influencing the therapeutic strategy of RA. Since chronic lung diseases are frequently associated with RA, the diagnosis of NTM pulmonary disease is quite difficult in RA patients. Recently, a serological diagnostic test detecting serum immunoglobulin A against the glycopeptidolipid (GPL) core antigen was developed. We investigated the serum levels of anti-GPL antibodies in RA patients to determine the usefulness for detecting NTM pulmonary disease.

Methods: Anti-GPL antibodies were detected in the sera from RA patients with or without NTM pulmonary disease.

Results: The positivity of anti-GPL antibodies in RA patients with NTM pulmonary disease was higher than in RA without (p?=?1.76?×?10^?14, odds ratio 70.29, 95% confidence interval [CI] 22.28–221.83). Anti-GPL Ab titers were increased in RA with NTM pulmonary disease (mean titer?±?standard deviation [U/ml], RA with NTM pulmonary disease: 4.1?±?7.0, RA without NTM pulmonary disease: 0.4?±?1.6, p?=?1.51?×?10^?10). The area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for anti-GPL antibodies was 0.917 (95%CI 0.860–0.974, p?=?3.32?×?10^?47).

Conclusions: Serum anti-GPL antibodies are useful for detecting NTM pulmonary disease in RA patients.     

Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review

Objectives: To identify, describe and summarize evidence on residual symptoms and disease burdens in rheumatoid arthritis (RA) patients qualified as being in remission or low disease activity (LDA).

Methods: A systematic literature review (SLR) was conducted according to Cochrane collaboration guidelines. The population of interest was adult patients with RA in remission or LDA. The reported outcomes of interest were any symptoms or burdens.

Results: Fifty-one publications were identified through an eDatabase search. Together with 17 articles found through other sources, 68 were included for full text review. The most commonly reported residual symptoms were pain (number of studies?=?25), fatigue (n?=?21) and morning stiffness (n?=?5). Reported disease burdens included mental health (n?=?15), sleep disturbances (n?=?7) and work productivity (n?=?5), impairment in quality of life (n?=?21), and functional disability (n?=?34). Substantial residual symptoms and disease burdens were found to be present in patients in remission or LDA.

Conclusion: This is the first SLR to investigate residual symptoms and disease burdens in RA patients in remission or LDA. The results indicate that despite achieving conventional clinical targets, the disease continues to affect patients, suggesting the existence of unmet need under the current treatment paradigm.     

Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)

Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index?<5 in Crohn’s disease (CD) and Patient Simple Clinical Colitis Activity index?<3 in ulcerative colitis (UC).

Results: Two-hundred forty-six patients (147?CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone?≥1 surgical resection. After a median follow-up of 17 (IQR: 14–20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p?<?.0001 in both groups). Faecal-calprotectin decreased in CD (p?<?.0001) and in UC (p?=?.001), whereas CRP decreased in CD (p?=?.002) but not in UC (p?=?.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96–16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10–4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16–6.48).

Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.     

Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who were refractory or intolerant to anti-tumor necrosis factor therapy: Subgroup analysis of a randomized,double-blind,multicenter, phase 3 study (SIRROUND-T)

Abstract

Objective: To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy.

Methods: This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed.

Results 116/878 patients received sirukumab 50?mg/4 weeks (q4w, n?=?35), 100?mg/2 weeks (q2w, n?=?44) or placebo (n?=?37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50?mg q4w:20 [57.1%]; p?<?.001, 100?mg q2w:24 [54.5%]; p?=?.001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50?mg q4w:29 [82.9%]; 100?mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs.

Conclusion: Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.     

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.