Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid arthritis

Abstract

Objective. Iguratimod (IGU) is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis (RA). We conducted a 24-week study on the efficacy of IGU in RA patients with daily clinical use.

Methods. Forty-one patients were enrolled in this study, and the improvement in RA was evaluated every 4 weeks during the 24 weeks.

Results. The patient's global assessment of the disease activity with a scale (Pt VAS) was significantly decreased beginning at week 4. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein (CRP), simplified disease activity index and clinical disease activity index all significantly decreased at week 24. The matrix metalloproteinase-3 level was significantly decreased by the combination treatment with methotrexate at week 24. According to a logistic regression analysis, the factor which was most associated with the achievement of low disease activity (DAS28-CRP < 2.7) at week 24 was the DAS28-CRP at week 0.

Conclusions. IGU had significant clinical effects on the RA patients within 24 weeks. IGU might therefore represent a new practical choice to treat RA patients.     

Efficacy and safety of mavrilimumab in Japanese subjects with rheumatoid arthritis: Findings from a Phase IIa study

Abstract

Objective. A phase IIa study investigated efficacy and safety/tolerability of ascending doses of mavrilimumab (anti-granulocyte-macrophage colony-stimulating factor receptor [GM-CSFR]α monoclonal antibody) in adult subjects with moderate to severe rheumatoid arthritis from Japan and Europe. Findings from the Japanese population are presented.

Methods. Fifty-one subjects received mavrilimumab (10–100 mg) or placebo subcutaneously every other week for 12 weeks, followed by a 12-week follow-up period. The primary endpoint was the proportion of subjects achieving a Disease Activity Score using 28 joints (DAS28)-C-reactive protein (CRP) response (decrease > 1.2 from baseline). Secondary endpoints included DAS28-CRP remission, Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR) response.

Results. By Week 12, more mavrilimumab- versus placebo-treated subjects achieved a DAS28-CRP response (50.0% vs. 23.5%, p = 0.081); a significant response was seen in the 30 mg and 100 mg dose groups (both 75.0% vs. 23.5%, p = 0.028). The 100 mg group also demonstrated statistically significant HAQ-DI and ACR20 responses at Week 12. Results were generally consistent between Japanese and European populations. Overall, adverse events (AEs) were mild to moderate in intensity with one serious AE of pneumonia, considered possibly treatment-related.

Conclusions. A rapid and clinically meaningful response was seen in subjects treated with GM-CSFRα blockade with mavrilimumab, supporting further investigation of mavrilimumab for the treatment of RA in Japanese subjects.     

Clinical efficacy,radiographic, and safety results of golimumab monotherapy in Japanese patients with active rheumatoid arthritis despite prior therapy with disease-modifying antirheumatic drugs: Final results of the GO-MONO trial through week 120

Objective: Evaluate the safety and efficacy of golimumab through week 120 in Japanese patients with active rheumatoid arthritis (RA) previously treated with DMARDs.

Methods: Japanese patients with active RA despite prior DMARDs were randomized to placebo (Group 1, n?=?105), golimumab 50?mg (Group 2, n?=?101), or golimumab 100?mg (Group 3, n?=?102). At week 16, Group 1 patients crossed over to golimumab 50mg; after week 52, a one-time golimumab dose reduction from 100 to 50?mg was permitted. Assessments included ACR20/50/70 responses and good/moderate DAS28-ESR responses. Radiographic progression was assessed with the van der Heijde-modified Sharp (vdH-S) score. Safety and efficacy were assessed through week 120.

Results: ACR20 response rates at week 52 in Group 1, Group 2, and Group 3 were 70.6%, 71.4%, and 81.9%, respectively, and maintained through week 104 (87.2%, 85.1%, 88.9%, respectively) and week 120 (86.1%, 87.0%, 89.5%, respectively). Similar trends were observed for ACR50, ACR 70, and DAS28-ESR. Median change in total vdH-S at weeks 52, 104, and 120 ranged from 0.0 to 1.5 across treatment groups. Through week 120, 93.8%/97.1% had an AE with golimumab 50?mg/100?mg, respectively, and 19.7%/11.8% had an SAE. Infections were the most common AE.

Conclusion: Clinical response to golimumab 50?mg and 100?mg was maintained over 2 years in Japanese patients with active RA despite prior DMARDs.     

Effectiveness and safety of initiating adalimumab plus ≥12 mg/week methotrexate with adjustable dosing in biologic-naïve patients with early rheumatoid arthritis: HAWK study postmarketing surveillance in Japan

Abstract

Objectives: This real-world study assessed the effectiveness and safety outcomes of initiating adalimumab and methotrexate (≥12?mg/week) with adjustable dosing in Japanese patients with early rheumatoid arthritis (RA).

Methods: This single-arm, prospective postmarketing observational study (conducted from September 2012 to March 2017 at 119 sites) enrolled biologic-naïve patients with early RA (≤2 years duration) and a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) >3.2 who were treated with methotrexate for ≥3 months and had initiated treatment with adalimumab and methotrexate (≥12?mg/week). This report presents 52-week data. The primary outcome was the proportion of patients who achieved DAS28-CRP scores <2.6 at week 52.

Results: Overall, 293 of 346 enrolled patients were included in the effectiveness population: women, 73%; mean (standard deviation) age, 54.3 (13.9) years; DAS28-CRP score, 4.51 (0.90); and modified total Sharp score (mTSS), 7.69 (9.98). At week 52, 77% of patients achieved clinical remission (DAS28-CRP <2.6), 92.3% achieved low disease activity (DAS28-CRP ≤3.2), and 86% of evaluable patients experienced structural remission (ΔmTSS ≤0.5).

Conclusion: Adalimumab plus methotrexate (≥12?mg/week) with adjustable dosing was well tolerated, and could be a beneficial treatment option for Japanese patients with early RA.

Trial registration: ClinicalTrials.gov identifier: NCT01736189.     

Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: A post hoc analysis of clinical trial data

Abstract

Objectives: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We investigated concomitant methotrexate (MTX) dose on tofacitinib efficacy/safety in Japanese RA patients.

Methods: This post hoc analysis pooled data from a 3-month phase 2 study (NCT00603512) and a 24-month phase 3 study (NCT00847613). Patients (N= 254) received tofacitinib (low-dose (1 or 3?mg), 5?mg, 10?mg) twice daily (BID) or placebo, with low-dose (>0 to 8?mg/week) or high-dose (>8?mg/week) MTX. Efficacy (ACR20/50/70 and DAS28-4 (ESR)<2.6 response rates; changes from baseline (CFB) in DAS28-4 (ESR) and HAQ-DI) and safety (adverse events (AEs), discontinuations due to AEs, serious AEs, and deaths) were assessed through month 3.

Results: At month 3, ACR20/50/70 response rates, mean DAS28-4 (ESR) CFB and HAQ-DI CFB were similar across MTX doses and generally greater for all tofacitinib doses versus placebo. AE rates with low-dose/high-dose MTX were: placebo, 28.6%/52.9%; tofacitinib low-dose, 50.0%/66.7%; 5?mg BID, 56.5%/64.3%; 10?mg BID, 73.8%/67.7%.

Conclusion: Tofacitinib efficacy in Japanese RA patients may be unaffected by background MTX dose. AE rates with low-dose versus high-dose MTX were lower with placebo, tofacitinib low-dose or 5?mg BID, but not 10?mg BID, with no apparent differences across system organ class/laboratory parameters.     

Efficacy,safety, pharmacokinetics and immunogenicity of abatacept administered subcutaneously or intravenously in Japanese patients with rheumatoid arthritis and inadequate response to methotrexate: a Phase II/III,randomized study

Abstract

Objective. To evaluate efficacy and safety of subcutaneous (SC) and intravenous (IV) abatacept and background methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).

Methods. Double-dummy, double-blind study (NCT01001832); 118 adults with ≥ 10 swollen joints, ≥ 12 tender joints and C-reactive protein (CRP) ≥ 0.8 mg/dL randomized 1:1 to SC abatacept (125 mg weekly) with IV loading (～10 mg/kg on Day 1), or IV abatacept (～10 mg/kg monthly) for 169 days, both also receiving MTX (6–8 mg/week). Primary endpoint was Day 169 American College of Rheumatology (ACR)20 response; other efficacy endpoints, safety and immunogenicity were assessed.

Results. Similar proportions of patients achieved ACR20 responses at Day 169 with SC (91.5% [95% CI 81.3, 97.2]) and IV abatacept (83.1% [71.0, 91.6]). ACR50/70 responses, adjusted mean changes from baseline in Health Assessment Questionnaire–Disability Index scores and remission rates (28-joint Disease Activity Score [CRP] < 2.6) were also comparable between groups. Serious adverse event frequencies (5.1% vs. 3.4%) were similar with both formulations. One patient per group tested seropositive for immunogenicity. Weekly SC abatacept dosing achieved mean serum concentrations > 10 μg/mL (minimum therapeutic target).

Conclusions. SC abatacept demonstrated comparable efficacy and safety to IV abatacept, with low immunogenicity rates, in MTX-IR Japanese patients with RA.     

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

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

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

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

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

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.     

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan: one-year clinical outcomes (RECONFIRM-2)

Abstract

Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-α chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria—good, moderate, and no response to infliximab—were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria.     

Efficacy and safety of baricitinib in Japanese patients with active rheumatoid arthritis: A 52-week,randomized, single-blind,extension study

Objectives: The objective of this study is to evaluate the efficacy and safety of long-term (64 weeks; 52-week extension of a 12-week study) baricitinib treatment in Japanese patients with active rheumatoid arthritis (RA) despite methotrexate therapy.

Methods: Patients (N?=?145) with active RA were randomized to placebo, 1mg, 2mg, 4mg, or 8mg baricitinib for the first 12 weeks. During the 52-week extension period, patients on 4mg or 8mg baricitinib remained on the same dose and all other patients were re-randomized to 4mg or 8mg baricitinib. Most patients on 8mg baricitinib were switched to 4mg by week 64 (protocol amendment); data analysis was based on the treatment group at the beginning of the extension period.

Results: Increases in the American College of Rheumatology (ACR) response rates (ACR20, ACR50, and ACR70) observed during the first 12 weeks were maintained during the extension period, accompanied by improvements in ACR core components. At week 64, a large proportion of patients (>40%) had low disease activity. Most treatment-related adverse events were mild or moderate; herpes zoster was the most common reason (11/27 patients) for discontinuation.

Conclusions: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy.

Clinicaltrials.gov NCT01469013; Funding: Eli Lilly and Incyte     

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

Abstract

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

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

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

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

Exercise Self-Efficacy and patient global assessment were associated with 6-min walk test distance in persons with rheumatoid arthritis

Introduction

Low functional capacity is related to future loss of daily function and cardiovascular events. The present study explored the associations of patient-reported outcome measures (PROMs) and disease-specific measures with functional capacity as measured by the 6-min walk test (6MWT) in persons with rheumatoid arthritis (RA).

Methods

Seventy-nine participants from rheumatology outpatient clinics were included. The distance walked during the 6MWT (6MWD) was the dependent variable in multivariable regression analyses. Model 1 included the independent variables sex, age (in tertiles to improve model fit), and body mass index (BMI). Building on Model 1, Model 2 added smoking, patient global assessment (PGA), Exercise Self-Efficacy, Hospital Anxiety and Depression Scale’s Depression score, and Cohen’s Perceived Stress Scale score, whereas Model 3 added smoking, disease duration, present use of glucocorticosteroids, seropositivity, Disease Activity Score 28—C-Reactive Protein (DAS28-CRP), and a comorbidity variable.

Results

Median age was 65 years, 76% were female, and median 6MWD was 493 m. In Model 1, BMI and age were significantly associated with the 6MWD (R² = 0.42). In Model 2, PGA and Exercise Self-Efficacy were also significantly associated with the 6MWD, with standardized regression coefficients of − 0.21 (p = 0.03) and 0.26 (p = 0.004) respectively (R² = 0.54). The RA-specific variables in Model 3 were not significantly associated with the 6MWD (R² = 0.49).

Conclusion

The PROMs PGA and Exercise Self-Efficacy were significantly associated with functional capacity as measured by the 6MWT in persons with RA, whereas disease-specific measures such as DAS28-CRP and disease duration were not.

Long-term efficacy and safety of certolizumab pegol in Japanese rheumatoid arthritis patients with an inadequate response to methotrexate: 52-week results from an open-label extension of the J-RAPID study

Abstract

Objectives. To evaluate the long-term efficacy and safety of certolizumab pegol (CZP) plus methotrexate treatment and to assess the efficacy of two CZP maintenance dosing schedules in Japanese rheumatoid arthritis (RA) patients with an inadequate response to methotrexate.

Methods. J-RAPID double-blind patients were entered into an open-label extension (OLE) study. Patients withdrawn due to lack of efficacy at 16 weeks and double-blind completers without a week-24 American College of Rheumatology (ACR) 20 response received CZP 200 mg every other week (Q2W) plus methotrexate. Double-blind completers with week-24 ACR20 responses were randomized to CZP 200 mg Q2W plus methotrexate or CZP 400 mg every 4 weeks plus methotrexate.

Results. The ACR20/ACR50/ACR70 response rates of double-blind completers (n = 204) were 89.7%/67.2%/36.3% at OLE entry and 95.6%/84.8%/58.3% at 52 weeks, respectively. Other clinical, functional and radiographic outcomes were sustained with long-term CZP plus methotrexate. Long-term treatment with CZP was well-tolerated with no new unexpected adverse events observed. The efficacy and safety of CZP treatment were similar between the two dosing schedules.

Conclusions. Continued CZP administration with methotrexate maintained efficacy over 52 weeks and was well-tolerated for Japanese RA patients. No obvious differences in clinical efficacy and safety were observed between the two dosing schedules, giving flexibility in maintenance administration schedules.     

Prediction of DAS28-CRP remission in patients with rheumatoid arthritis treated with tacrolimus at 6 months by baseline variables

Abstract

We attempted to determine what baseline variables are responsible for the efficacy of tacrolimus at 6 months in Japanese patients with rheumatoid arthritis (RA). One hundred and six RA patients treated with tacrolimus for 6 months were entered in this study. The outcome was set as the achievement of Disease Activity Score 28 C-reactive protein (DAS28-CRP) remission at 6 months. We examined the association of gender, DAS28-CRP at baseline, concomitant use of methotrexate (MTX), and concomitant use of prednisolone with the achievement of DAS28-CRP remission at 6 months by logistic regression analysis. Twenty-three of 106 patients (21.7%) achieved DAS28-CRP remission at 6 months. There was concomitant use of MTX by 20 patients (18.9%), prednisolone by 93 (87.7%), and prednisolone >5 mg/day by 43 (40.6%) at baseline. Logistic regression analysis showed that male gender (first) and moderate disease activity at baseline (second) are independent predictors toward achieving DAS28-CRP remission at 6 months. Maximum tacrolimus dosage administrated for patients over a 6-month period appeared not to be predictive for the DAS28-CRP remission at 6 months. In conclusion, we revealed for the first time that good outcome in RA patients treated with tacrolimus can be predictive by some baseline variables. That is clinically valuable for daily practice in the choice of disease-modifying antirheumatic drugs (DMARDs), especially tacrolimus.     

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.     

Efficacy at 52 weeks of daily clinical use of iguratimod in patients with rheumatoid arthritis

Abstract

Objective. In recent years, the use of one or more conventional synthetic disease-modifying antirheumatic drugs has been recommended for the treatment of rheumatoid arthritis (RA). We performed a 52-week study on the efficacy and safety of iguratimod (IGU) against patients with RA in daily clinical use.

Methods. Forty-one patients were enrolled in this study, and the clinical course of RA was regularly evaluated during the 52 weeks of treatment.

Results. The survival rate at week 52 was 53.7%. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein, simplified disease activity index, and clinical disease activity index were all significantly decreased at week 52. The matrix metalloproteinase-3 level was significantly decreased at week 52 by combination therapy of IGU and methotrexate. There were one case of the onset of interstitial pneumonia (IP), one exacerbation of IP, and one case of the onset of Pneumocystis jiroveci pneumonia.

Conclusions. IGU is effective for RA patients when used for daily clinical treatment for 52 weeks.     

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.     

Safety and effectiveness of abatacept in Japanese non-elderly and elderly patients with rheumatoid arthritis in an all-cases post-marketing surveillance

Abstract

Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis patients.

Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2.

Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p?=?.021) and infections (4.8% vs. 7.2%, p?=?.002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline.

Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.     

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.     

Fractures lead to worsening of disease activity in rheumatoid arthritis

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

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

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

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