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Relapse of neuromyelitis optica spectrum disorder occurred in 20% of patients who received satralizumab, a subcutaneous anti–interleukin-6 antibody, as compared with 43% of those in the placebo group. The drug may have been more effective in patients with anti–aquaporin-4 IgG antibody than in those without the antibody.

Background Abatacept (ABA) is a biological disease-modifying antirheumatic drug (bDMARD) for rheumatoid arthritis (RA). The aim of this study was to identify molecules that are associated with therapeutic responses to ABA in patients with RA. Methods Peripheral blood was collected using a PAX gene Blood RNA kit from 45 bDMARD-naïve patients with RA at baseline and at 6 months after the initiation of ABA treatment. Gene expression levels of responders ( n  = 27) and non-responders ( n  = 8) to ABA treatment among patients with RA at baseline were compared using a microarray. The gene expression levels were confirmed using real-time quantitative polymerase chain reaction (RT-qPCR). Results Gene expression analysis revealed that the expression levels of 218 genes were significantly higher and those of 392 genes were significantly lower in the responders compared to the non-responders. Gene ontology analysis of the 218 genes identified “response to type I interferon (IFN)” with 24 type I IFN-related genes. RT-qPCR confirmed that there was a strong correlation between the score calculated using the 24 genes and that using OAS3 , MX1 , and IFIT3 (type I IFN score) (rho with the type I IFN score 0.981); the type I IFN score was significantly decreased after treatment with ABA in the responders ( p  < 0.05), but not in the non-responders. The receiver operating characteristic curve analysis of the type I IFN score showed that sensitivity, specificity, and AUC (95% confidence interval) for the responders were 0.82, 1.00, and 0.92 (0.82–1.00), respectively. Further, RT-qPCR demonstrated higher expression levels of BATF2 , LAMP3 , CD83 , CLEC4A , IDO1 , IRF7 , STAT1 , STAT2 , and TNFSF10 in the responders, all of which are dendritic cell-related genes or type I IFN-related genes with significant biological implications. Conclusion Type I IFN score and expression levels of the nine genes may serve as novel biomarkers associated with a clinical response to ABA in patients with RA.

Abstract A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.

Abstract A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.

Background Sulfamethoxazole-trimethoprim (SMX/TMP) is a standard drug for the prophylaxis of Pneumocystis pneumonia (PJP) in immunosuppressed patients with systemic rheumatic diseases, but is sometimes discontinued due to adverse events (AEs). The objective of this non-blinded, randomized, 52-week non-inferiority trial was to quest an effective chemoprophylaxis regimen for PJP with a low drug discontinuation rate. Results at week 24 were reported. Methods Adult patients with systemic rheumatic diseases who started prednisolone ≥0.6 mg/kg/day were randomized into three dosage groups: a single-strength group (SS, SMX/TMP of 400/80 mg daily), half-strength group (HS, 200/40 mg daily), and escalation group (ES, started with 40/8 mg daily, increasing incrementally to 200/40 mg daily). The primary endpoint was non-incidence rates (non-IR) of PJP at week 24. Results Of 183 patients randomly allocated at a 1:1:1 ratio into the three groups, 58 patients in SS, 59 in HS, and 55 in ES started SMX/TMP. A total of 172 patients were included in the analysis. No cases of PJP were reported up to week 24. Estimated non-IR of PJP in patients who received daily SMX/TMP of 200/40 mg, either starting at this dose or increasing incrementally, was 96.8–100% using the exact confidence interval as a post-hoc analysis. The overall discontinuation rate was significantly lower with HS compared to SS ( p  = 0.007). The discontinuation rates due to AEs were significantly lower with HS ( p  = 0.006) and ES ( p  = 0.004) compared to SS. The IR of AEs requiring reduction in the dose of SMX/TMP ( p  = 0.009) and AEs of special interest ( p  = 0.003) were different among the three groups with significantly higher IR in SS compared to HS and ES. Conclusions Although there were no PJP cases, the combined group of HS and ES had an excellent estimated non-IR of PJP and both were superior in safety to SS. From the perspective of feasibility and drug discontinuation rates, the daily half-strength regimen was suggested to be optimal for prophylaxis of PJP in patients with systemic rheumatic diseases. Trial registration The University Hospital Medical Information Network Clinical Trials Registry number is UMIN000007727 , registered 10 April 2012.

Introduction The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice. Methods This prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry. We assessed types and incidence rates (IRs) of serious adverse events (SAEs) and serious infections (SIs) during the first year of treatment. Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis. Results Patients in the TCZ group had longer disease duration ( P  <0.001), higher disease activity ( P  = 0.019) and more frequently used concomitant corticosteroids ( P  <0.001) than those in the TNFI group. The crude IR (/100 PY) of SIs [TCZ 10.68 vs. TNFI 3.03; IR ratio (95% confidence interval [CI]), 3.53 (1.52 to 8.18)], but not SAEs [21.36 vs. 14.72; 1.45 (0.94 to 2.25)], was significantly higher in the TCZ group compared with the TNFI group. However, after adjusting for covariates using the Cox regression hazard analysis, treatment with TCZ was not associated with higher risk for SAEs [hazard ratio (HR) 1.28, 95% CI 0.75 to 2.19] or SIs (HR 2.23, 95% CI 0.93 to 5.37). Conclusions The adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs, indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice.

Objective To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). Method This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan–Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. Results The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. Conclusions Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.

A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.

A 64-year-old woman with rheumatoid arthritis (RA) began to complain of recurrent non-productive cough 5 months after starting adalimumab. The chest radiograph and high-resolution computed tomographic findings revealed diffuse ground-glass attenuation. Her clinical course suggested that interstitial pneumonia (IP) may have been induced by adalimumab, and she was successfully treated with a medium dose of corticosteroid. This case indicates that adalimumab-associated IP should be considered if a RA patient develops non-productive cough following adalimumab therapy.

BackgroundIn the treat-to-target strategy (T2T)1, simplified disease activity index (SDAI) has been proposed as one of measures to define remission2. Predictive ability of SDAI remission for functional and structural outcomes was shown by data from clinical trials, but has not been proven in a T2T implementing cohort.ObjectivesTo examine if achieving SDAI remission is a predictor of good functional and structural outcomes in a T2T implementing cohort.MethodsThe T2T Epidemiological Study is a multi-centre, prospective cohort study, in which RA patients with moderate to high disease activity were enrolled and treated with T2T for 72 weeks. The disease activity was assessed every 12 weeks and the treatment was adjusted accordingly. Primary outcomes were HAQ and ΔmTSS at week 72. Multivariate logistic regression analysis was used to examine association between SDAI remission at week 24 and the two primary outcomes. Missing data were imputed using the multiple imputation method. Statistical significance levels were adjusted for multiple comparison using False Discovery Rate and BH methods.ResultsOf total 318 enrolled patients, 244 patients followed up for 72 weeks were analysed. Patient characteristics were as follows: female, 77%; mean age, 61; mean disease duration, 57 months. At week 24, 33% achieved SDAI remission. At week 72, 50% achieved SDAI remission, 61% achieved HAQ remission (≤0.5) and 73% showed ΔmTSS

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