Effectiveness of golimumab in rheumatoid arthritis patients with inadequate response to first-line biologic therapy: Results from a Japanese post-marketing surveillance study.

OBJECTIVES: To assess the real-world effectiveness of golimumab in Japanese patients with rheumatoid arthritis who had previously received first-line biologic therapy. METHODS: A post-hoc analysis of post-marketing surveillance was performed. The effectiveness of golimumab was assessed in 731 patients with an inadequate response to first-line biologic therapy stratified by their prior biologic agents. Outcome variables included DAS28-CRP, DAS28-ESR, SDAI and CDAI, and medication persistence. Logistic regression analyses were conducted to identify factors associated with the likelihood of achieving a DAS28-CRP response (good/moderate) after 24 weeks of golimumab treatment. RESULTS: Patients demonstrated significant improvement in the clinical signs and symptoms of rheumatoid arthritis at 24 weeks, as indicated by the reduction of DAS28-CRP (Δ0.87), DAS28-ESR (Δ0.85), SDAI (Δ7.32), and CDAI (Δ6.98) scores. This result was consistent across the subgroups stratified by previous biologic therapy. Multivariate analysis failed to identify any factors associated with response to golimumab. CONCLUSION: In the real-world clinical setting, switching to golimumab was effective for Japanese patients with an inadequate response to first-line biologic therapy regardless of the biologic agent, including both TNF and non-TNF inhibitors.

Clinical response among golimumab-treated Japanese patients with rheumatoid arthritis by number of previous biologic therapies: Real-world evidence from post-hoc analysis of post-marketing surveillance data.

OBJECTIVES: To assess the real-world effectiveness of golimumab in Japanese patients with rheumatoid arthritis who had previously received one or more biologic therapies. METHODS: A post-hoc analysis of post-marketing surveillance was performed. The clinical response to golimumab was analyzed in 1216 patients who had previously received one or more biologic agents including non-TNF inhibitors with stratification by the number of previous biologic agents. Logistic regression analyses were conducted to identify factors associated with DAS28-CRP response to golimumab. RESULTS: While treatment persistence is comparable, the response to golimumab declined with an increasing number of previous biologic therapies. When stratified by golimumab dose, patients receiving golimumab at 100 mg had higher disease activity at baseline with an increasing number of previous bDMARDs, but they still achieved comparable disease activity at 24 weeks regardless of how many bDMARDs had been previously used. Univariate and multivariate analyses both identified concomitant oral corticosteroid therapy as a factor negatively associated with the likelihood of achieving a DAS28-CRP response. CONCLUSION: Switching to golimumab was effective regardless of how many biologic agents had been previously used, but the response declined with an increasing number of prior biologic agents. A golimumab dose of 100 mg was also effective for those who previously received three or more bDMARDs.

Correction to: Effect of Golimumab Dose Escalation in Japanese Patients With Rheumatoid Arthritis: Post-Hoc Analysis of Post-Marketing Surveillance Data.

Under Results section, heading: Effectiveness of GLM Stratified by the Time to Dose Escalation, the remission based on values of DAS28, SDAI, and CDAI was published incorrectly. The correct values are: 16.1%, 5.0% and 4.3.

Effect of Golimumab Dose Escalation in Japanese Patients With Rheumatoid Arthritis: Post-Hoc Analysis of Post-Marketing Surveillance Data.

INTRODUCTION: While dose escalation of golimumab has been used for patients with rheumatoid arthritis who demonstrate an inadequate response to the standard dose, its effectiveness has not been fully evaluated. The aim of this study was to assess the clinical outcome observed by dose escalation of golimumab for patients with rheumatoid arthritis in the daily clinical setting. METHODS: A post hoc analysis was performed of data from the 24-week post-marketing surveillance conducted in Japan (n = 5154). A total of 301 patients with moderate or high disease activity at baseline who underwent dose escalation of golimumab were assessed for effectiveness at 24 weeks based on several variables, such as DAS28-CRP, SDAI, and CDAI, as well as for medication persistence through 24 weeks. In addition, the study population was stratified by the time to dose escalation, and effectiveness was likewise evaluated. Logistic regression analysis was performed to identify factors associated with a moderate/good EULAR response to golimumab at 24 weeks. RESULTS: Patients with golimumab dose escalation showed significant improvement of the clinical signs and symptoms of rheumatoid arthritis at 24 weeks, as indicated by reduction of the DAS28-CRP (∆0.89), SDAI (∆8.64), and CDAI (∆8.28) scores. This result was relatively consistent across the subgroups stratified by the timing of dose escalation. According to Kaplan-Meier analysis, 78.1% of the patients continued to receive golimumab at 24 weeks, and this was also similar among the subgroups stratified by the time to dose escalation. Multivariate analysis identified male sex and previous biologic therapy as factors that were significantly associated with the clinical response at 24 weeks. CONCLUSION: In real-world clinical practice, improvement of disease activity was observed after uptitration of golimumab from 50 to 100 mg regardless of the timing. Male patients and biologic-naive patients were more likely to respond to dose escalation of golimumab. TRIAL REGISTRATION: UMIN-CTR, Identifier: UMIN000015895.

Safety, Effectiveness, and Treatment Persistence of Golimumab in Elderly Patients with Rheumatoid Arthritis in Real-World Clinical Practice in Japan.

INTRODUCTION: Golimumab has been proven as an effective treatment for rheumatoid arthritis in clinical trials. However, there is a scarcity of data regarding its use in elderly patients in a real-world setting. This study aims to evaluate the safety, effectiveness, and treatment persistence of golimumab in elderly Japanese patients (≥ 75 years) with rheumatoid arthritis. METHODS: This study was a post hoc analysis of post-marketing surveillance data on 5137 Japanese patients with active rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided into two age groups (younger: < 75 years and elderly: ≥ 75 years), and the safety, effectiveness, and treatment persistence of golimumab were assessed. Also, the reasons for discontinuing golimumab treatment were analyzed by multi-logistic regression. RESULTS: During golimumab treatment over 24 weeks, younger and elderly groups exhibited comparable improvement of disease activity as measured by EULAR response criteria with similar overall rates of adverse events. However, the survival curve of golimumab for elderly patients was significantly different from that for younger patients due largely to the discontinuation at 4 weeks. The most common reason for discontinuation in elderly patients was patient choice, while it was disease progression in younger patients. Analysis of elderly patients who discontinued treatment by their own decision identified EULAR good response as a factor associated with continuation of golimumab treatment whereas no predictive factor associated with discontinuation was identified. CONCLUSIONS: The safety and effectiveness of golimumab treatment in elderly Japanese patients aged 75 years or older were comparable to those in younger patients in real-world clinical practice. Analysis of the survival curves suggested that continuous use of golimumab might further improve clinical benefit of golimumab in elderly patients, underpinning the importance of effective communication between physicians and elderly patients based on the treat-to-target strategy. FUNDING: Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.

Real-World Treatment Patterns for Golimumab and Concomitant Medications in Japanese Rheumatoid Arthritis Patients.

INTRODUCTION: The aim of this study was to investigate real-world treatment patterns for use of golimumab and concomitant medications in Japanese patients with rheumatoid arthritis. METHODS: This study was a post hoc retrospective analysis from post-marketing surveillance data on 2350 Japanese patients with moderate/severe rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided based on initiation treatment or dose adjustment patterns with golimumab, methotrexate, or oral glucocorticoids. RESULTS: Logistic regression analysis revealed that the baseline factors associated with administration of golimumab (100 mg) were higher body weight, failure of prior biological therapy (bio-failure), no previous methotrexate use, and respiratory disease, while previous methotrexate use and absence of renal impairment or respiratory disease were associated with concomitant methotrexate therapy, and previous glucocorticoid use was associated with concomitant glucocorticoid therapy. The following associations were identified with regard to dose adjustment during treatment: bio-failure, no previous methotrexate use, previous csDMARDs use, presence of respiratory disease, allergy history, and higher CRP for golimumab dose escalation; shorter disease duration, previous GC, and no previous methotrexate use for methotrexate dose escalation; no prior biological therapy and renal impairment for methotrexate dose reduction; no previous GC use for glucocorticoid dose escalation; and absence of Steinbrocker's stage II/III/IV, absence of Steinbrocker's class II, no bio-failure, and no previous csDMARDs use for glucocorticoid dose reduction. CONCLUSIONS: This study revealed that various baseline factors were associated with initiation of treatment and dose adjustment of golimumab, methotrexate, or oral glucocorticoids, reflecting both the treatment strategies of physicians for improving RA symptoms and/or reducing adverse events. FUNDING: Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.

Postmarketing surveillance evaluating the safety and effectiveness of golimumab in Japanese patients with rheumatoid arthritis.

OBJECTIVES: The purpose of this study was to evaluate the real-world safety and effectiveness of golimumab (GLM) in Japanese patients with rheumatoid arthritis. METHODS: A postmarketing surveillance of 5154 patients was conducted with a follow-up duration of at least 24 weeks. Patients were divided into four groups based on the initial treatment: 50 mg or 100 mg of GLM with concomitant use of methotrexate (MTX) and 50 mg or 100 mg of GLM monotherapy. Patient characteristics at baseline, safety and effectiveness were assessed for each group. RESULTS: Over 70% of patients received 50 mg of GLM with concomitant MTX, and approximately, 20% received monotherapy. The incidence rate of adverse events was 45.40 per 100 patient-years. The incidence of adverse events including serious adverse events was comparable across all groups. The proportion of patients showing remission or low disease activity increased from 13.69% to 46.21% at the final evaluation, and no differences were observed in the percentage of remission across the four groups. Concomitant MTX use was associated with higher probability of continuing therapy. CONCLUSIONS: GLM showed effectiveness in Japanese rheumatoid arthritis patients with an acceptable safety profile.

Determination of hypnotic benzodiazepines (alprazolam, estazolam, and midazolam) and their metabolites in rat hair and plasma by reversed-phase liquid-chromatography with electrospray ionization mass spectrometry.

Sensitive determination of benzodiazepines i.e., alprazolam (ALP), estazolam (EST), and midazolam (MDZ), and their metabolites, was carried out by reversed-phase liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS). The chromatography separations were achieved using a semi-micro HPLC column (3 microm particle size; 100 x 2.0 mm, i.d.) with acetonitrile-water containing 1% acetic acid as eluent. The mass spectrometer was operated in selected-ion monitoring mode at protonated-molecular ions [M+H](+) of parent drugs and the metabolites. The proposed procedure was applied to the determination in hair shaft of Dark Agouti rats after intraperitoneal (i.p.) administration of benzodiazepines twice a day for 5 days. Various metabolites together with parent drugs were identified in the hair shaft, 1-hydroxyalprazolam (1-HA) and 4-hydroxyalprazolam (4-HA) from ALP administration; 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine-4-one (K-EST) from EST administration; 1-hydroxymidazolam (1-HM) and 4-hydroxymidazolam (4-HM) from MDZ administration. A few unknown metabolites were also detected in the hair samples. These structures were elucidated with acetylation using acetic anhydride and pyridine. The time course studies of parent drugs and the metabolites in both hair root and plasma were also carried out after single i.p. administration of benzodiazepines. The results suggested that the concentrations of parent drugs and the metabolites in the hair samples were mainly dependent upon those in the plasma.