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.     

Disease activity score 28 may overestimate the remission induction of rheumatoid arthritis patients treated with tocilizumab: comparison with the remission by the clinical disease activity index

We evaluated the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) by the clinical disease activity index (CDAI) and disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR). Thirty-two RA patients received 8?mg/kg of TCZ intravenously every 4?weeks for 48?weeks. The therapeutic response was also evaluated in 30 RA patients treated with 3?mg/kg of infliximab (IFX) for 46?weeks. We compared the therapeutic course of TCZ with IFX in order to evaluate the efficacy of TCZ therapy. A strong positive correlation between CDAI and DAS28-ESR was observed at baseline, whereas their associations dropped significantly within the first 2?months. The association recovered to the baseline by IFX, but still remained low in TCZ. Although a decrement of DAS28-ESR was prominent in TCZ as compared with IFX, that of CDAI was significant in the early phase and even in the latter in patients treated by IFX. The present study revealed that DAS28-ESR may not be sufficient to estimate RA disease activity treated by TCZ, probably due to the significant effect toward inhibition of acute phase reactants by TCZ. CDAI is suggested to be an important alternate of composite measure in these cases.     

Evaluation of disease activity indices in Korean patients with rheumatoid arthritis

The aim of this study is to examine the validity of the rheumatoid arthritis (RA), disease activity score (DAS), 28-C-reactive protein (CRP), the simplified disease activity index (SDAI), and the clinical disease activity index (CDAI) against the DAS28-erythrocyte sedimentation rate (ESR) and determine cut-off values for each tool in Korean patients with RA. A total of 223 RA patients were consecutively recruited from the Hanyang University Hospital for Rheumatic Diseases in Seoul, Korea. DAS28-CRP, SDAI, and CDAI were measured and compared with DAS28-ESR. The correlation coefficients of DAS28-ESR with DAS28-CRP, SDAI, and CDAI were 0.93, 0.85, and 0.84, demonstrating strong linear relationships. The cut-off values of DAS28-CRP classifying RA patients into four categories of disease activity were defined as 2.19, 2.60, and 4.07. SDAI cut-off values were defined as 3.75, 7.50, and 16.88. CDAI cut-off values were defined as 3.62, 7.38, and 16.50. DAS28-CRP, SDAI, and CDAI are valid and sensitive assessment indices of disease activity that are comparable to DAS28-ESR. The cut-off values of each tool derived in this study might be useful for routine monitoring and therapeutic decision-making in Korean RA patients.     

Comparison of composite disease activity indices for rheumatoid arthritis

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.     

Changes in serum interleukin-6 levels as possible predictor of efficacy of tocilizumab treatment in rheumatoid arthritis

Objectives: We aimed to evaluate the association between the change in serum IL-6 during the clinical course of tocilizumab (TCZ) therapy and rheumatoid arthritis (RA) disease activity or occurrence of adverse events.

Methods: General laboratory data including serum IL-6 levels and physical findings were obtained every 4 weeks, and, in addition, at the time when any adverse events occurred.

Results: The proportion achieving Clinical Disease Activity Index (CDAI) remission at 52 weeks was significantly lower in 20 patients with serum IL-6?≥?30?pg/ml at 12 weeks than 24 patients with serum IL-6?Conclusion: Serum IL-6 levels from 12 to 24 weeks after TCZ initiation better reflect the efficacy of TCZ at 52 weeks.     

Reexamination of the assessment criteria for rheumatoid arthritis disease activity based on comparison of the Disease Activity Score 28 with other simpler assessment methods

Objective

To explore simpler and possibly more appropriate tools than the conventional Disease Activity Score 28 (DAS28) for assessing rheumatoid arthritis (RA) and to derive more reliable DAS28-based criteria.

Methods

The capabilities of assessing disease activities in 250 RA patients were compared between DAS28 and other methods, including the Simplified DA Index (SDAI), Clinical DA Index (CDAI), and Routine Assessment of Patient Index Data-3 (RAPID-3).

Results

SDAI and CDAI showed a good correlation and consistency with DAS28, whereas RAPID-3 yielded inferior results. In terms of remission criteria, DAS28 was less stringent than SDAI or CDAI; when RA remission was reexamined based on more stringent SDAI or CDAI criteria, cut-off values for DAS28-C-reactive protein of <1.72 were considered to be appropriate. The conventional DAS28 was considered to be appropriate for assessing low, middle and high disease activities because it provides criteria similar to or more stringent than those of other methods, while SDAI and CDAI were considered to be simpler and more appropriate criteria for assessing remission.

Conclusion

For assessing remission, DAS28-CRP provides the most appropriate criterion of the methods compared when the currently used cut-off value of 2.3 is lowered to a new value of 1.72.     

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.     

Revising DAS28 scores for remission in rheumatoid arthritis

Current initiatives to treat rheumatoid arthritis (RA) to target remission have resulted in the widespread use of composite outcome measures to quantify disease activity. Simplified Disease Activity Index (SDAI) ≤3.3 is the gold standard of remission. Previous work has suggested that the remission threshold of DAS28-ESR or DAS28-CRP ≤2.6 is known to be not strict enough and should be revised. There is no previous study that looks at the equivalent DAS28-CRP value that best reflects SDAI remission in a real-life cohort. Consecutive cases fulfilling ACR/EULAR classification criteria for RA from one centre were included if they had an optimum number of visits with recording of all raw data to calculate DAS28-ESR, DAS28-CRP and SDAI. Data from seven visits each of 76 patients, providing 532 data points was examined. Spearman’s correlation between DAS28-ESR, DAS28-CRP and SDAI was 0.91–0.97 (p?<?0.001). A Bland-Altman plot demonstrated a mean difference of 0.37 units between DAS28-ESR and DAS28-CRP (p?<?0.001). ROC and kappa analysis provided values of 2.58 and 2.55 for DAS28-ESR4V and 2.09 and 2.05 for DAS28-CRP4V for SDAI value of 3.3, respectively. The two versions of DAS28 using ESR and CRP and SDAI correlate but are not equivalent or interchangeable for an individual patient. The DAS28-CRP overestimates remission and should be revised downwards to a proposed value of 2.1.     

Evaluation of switching from intravenous to subcutaneous formulation of tocilizumab in patients with rheumatoid arthritis

Objective: To evaluate the efficacy of switching the route from intravenous tocilizumab (TCZ) infusion (TCZ-IV) to subcutaneous TCZ injection (TCZ-SC) in a real-world setting through a comparison of the clinical response.

Methods: Fifty-eight rheumatoid arthritis (RA) patients, for whom TCZ-SC was initiated following TCZ-IV between June 2013 and August 2014, were consecutively enrolled. Disease activity score (DAS)28-ESR, simplified disease activity index (SDAI), and clinical disease activity index (CDAI) were examined at baseline and after switching from TCZ-IV to TCZ-SC for 3 months. We investigated whether body weight and body mass index (BMI) affected the efficacy of TCZ-SC.

Results: Most of the patients had achieved remission or low disease activity at baseline (77.6% examined by DAS28). Fifty-seven patients (98%) continued the TCZ-SC treatment, and the disease activity was well controlled after 3 months. ΔDAS28 tended to be worsened after switching to TCZ-SC in the high-body-weight groups (≥60?kg) as compared with the groups with body weight?<60?kg, although no statistical significance was found. BMI did not affect the efficacy of TCZ-SC.

Conclusions: Caution should be exercised in the high-body-weight subjects, but these data indicate that TCZ-SC maintains the favorable RA disease activity established using TCZ-IV.     

Shorter disease duration is important for tocilizumab to achieve Boolean remission

Objective

To determine the optimal conditions for inducing rheumatoid arthritis (RA) into disease remission by tocilizumab (TCZ), we analyzed the TCZ therapy carried out in our facility.

Method

The study group comprised 116 patients with RA who started TCZ therapy at Kobe University Hospital and Konan-Kakogawa Hospital. The clinical response to TCZ was evaluated by the 2011 Boolean definition and the disease activity score of 28 joints erythrocyte sedimentation rate 4 (DAS28-ESR4).

Results

After 24 weeks of TCZ therapy, 25.9 % of the patients achieved a Boolean-defined disease remission (Boolean remission). DAS28-ESR4 was improved from 5.25 ± 1.15 at week 0 to 2.75 ± 1.34 at week 24 (mean ± SD, P < 0.0001), and 57.8 % patients achieved DAS28 remission. Analysis of the relationship between disease duration and remission showed that this odds ratio peaked at 3.0 years. Univariate analyses showed that Boolean remission was associated with baseline ESR levels, Steinbrocker’s class and stage, and patient global assessment of disease activity (PGA). Accordingly, we categorized and compared the patient groups referring to the 3.0-year peak. We found significant differences in Steinbrocker’s class and stage.

Conclusion

TCZ therapy leading to Boolean disease remission is optimal when initiated less than 3.0 years after disease onset.     

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.     

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.     

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.     

Patient-centered rheumatoid arthritis disease activity assessment by a modified RADAI

OBJECTIVE: To evaluate the psychometric properties and validity of a modified version of the Rheumatoid Arthritis Disease Activity Index (RADAI) without joint counts in order to facilitate rapid and easy RA activity assessment in daily routine. METHODS: One hundred sixty-nine outpatients with RA completed the original RADAI and the modified RADAI-5. Simultaneously, the Disease Activity Score-28-erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI) and Clinical DAI (CDAI) were applied. Cronbach's alpha, as a measure for internal consistency, and Spearman's rho, to evaluate the linear relationship of the different disease activity scales, were calculated. Rho was determined for the RADAI-5 and the core set measures to assess convergent validity. For agreement analysis, kappa statistics were calculated. An attempt was made to estimate the modified questionnaire's sensitivity to change. RESULTS: Means for the RADAI and the RADAI-5 were 2.8 (range 0.0-9.12) and 3.07 (0-10), respectively. Other means were as follows: DAS28-ESR 3.51 (0.28-6.67), DAS28-CRP 3.19 (1.12-5.83), CDAI 11.53 (0.0-44.6), and SDAI 12.36 (0.1-44.9). Cronbach's alpha was highest for the RADAI-5 (0.917) and lowest for the DAS28-CRP (0.510). The RADAI-5 was highly significantly correlated (all p < 0.0001) to all other instruments. However, kappa was < 0.65 for the relation of the RADAI-5 and all other scores except the RADAI. Changes of the RADAI-5, DAS28-ESR, and CDAI were significantly correlated (p < 0.001). CONCLUSION: The RADAI-5, refraining from joint counts, was shown to be capable of measuring RA activity. Reliability and convergent validity could be proven.     

Comparison between different disease activity scores in rheumatoid arthritis: an Egyptian multicenter study

The aim of our work was to assess the performance of different Disease Activity Score (DAS) other than DAS-ESR in daily clinical practice in our Egyptian outpatient clinics and also to evaluate the accuracy of European League Against Rheumatism Classification (EULAR) proposed cutoffs for these scores to stratify Egyptian patients into different categories of disease activity. This study is a cross-sectional Egyptian multicenter study. It included 130 rheumatoid arthritis (RA) patients who visited our Rheumatology and Rehabilitation outpatient and inpatient clinics; 80 patients from Cairo University Hospitals and 50 patients from Zagazig University Hospitals. The patients fulfilled the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism Classification criteria for rheumatoid arthritis. Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) were calculated. A significant positive correlation was found between all three scores and morning stiffness, ESR, Modified Health Assessment Questionnaire (MHAQ), and DAS-ESR. Also, there was a significant negative correlation between DAS-CRP and hemoglobin and a significant positive correlation with CRP. Also, there was a highly significant moderate agreement between DAS-ESR and DAS-CRP using Fleischmann et al. thresholds and also between DAS-ESR and SDAI. While a highly significant fair agreement was found between DAS-ESR and DAS-CRP using DAS-ESR thresholds and between DAS-ESR and CDAI. We conclude that DAS-CRP, SDAI, and CDAI are very useful in representing disease activity in RA patients in our outpatient clinics being well correlated with many markers of disease activity. We recommend huge multicenter studies in Egypt and in different populations to define new cutoff values to optimize their use in clinical setting.     

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.     

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.     

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.     

Interleukin‐6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute‐phase reactants

Objective

To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute‐phase reactants.

Methods

Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease‐modifying antirheumatic drugs. The CDAI does not contain an acute‐phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used.

Results

Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute‐phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab‐treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab‐treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission.

Conclusion

Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

     

Visualization of DAS28, SDAI,and CDAI: the magic carpets of rheumatoid arthritis

There has been continuous debate regarding the applicability of various composite measures for the assessment of disease activity in rheumatoid arthritis (RA). In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. We wished to graphically visualize the relative contribution of various elements in the three activity indices to each other. We calculated DAS28 (3 variables), SDAI, and CDAI by the standard equations. We plotted 3D “carpets” showing all combinations of the corresponding variables yielding to DAS28?=?5.1, DAS28?=?3.2, DAS28?=?2.6, SDAI?=?26, SDAI?=?11, and SDAI?=?3.3. We also plotted the 3D carpet for CDAI. In patients with high or moderate disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was not a major confounding factor when calculating DAS28 and SDAI, respectively. In contrast, ESR and CRP highly overshadowed changes in joint counts and global assessments in patients with low disease activity (LDA) or those in remission. No reliable assessment of LDA can be performed in cases where ESR >54 mm/h or CRP >20 mg/dl. Similarly, remission cannot be determined if ESR >19 mm/h or CRP >5 mg/dl. As CDAI does not include acute phase reactants, CDAI may be a useful tool even in states of remission or LDA. Our results suggest that acute phase reactants are indeed major confounding factors and should be omitted when assessing RA disease activity at least in special cases.