Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: A 52-week analysis of a postmarketing surveillance study in Japan.

Adalimumab is a human monoclonal antibody against tumor necrosis factor-α that was approved in Japan for the treatment of hidradenitis suppurativa (HS), a chronic recurrent inflammatory skin disease. We report the results of the final analysis of the postmarketing surveillance (PMS) study (ClinicalTrials.gov: NCT03894956), which evaluated the 52-week safety and efficacy of adalimumab for HS treatment in real-world clinical practice in Japan. This multicenter, prospective, open-label, observational study (March 2019 to May 2021) included patients with HS treated with subcutaneous adalimumab at doses following the package insert. The primary endpoint was safety, and the secondary endpoints were effectiveness, including HS clinical response (HiSCR), C-reactive protein (CRP), skin pain, and Dermatology Life Quality Index (DLQI). Of the 84 patients registered at 65 sites, 83 patients were included in the analyses. Adverse drug reactions (ADRs) were reported by 10 (12.0%) patients; two patients reported a serious ADR, including one patient with serious infection. Other safety events of special interest reported were liver disorder and dermatitis psoriasiform (one patient each). Almost all patients with ADRs were recovering or had recovered, except for one patient who experienced a serious ADR of liver disorder and died. At 12 weeks, 55.4% of patients achieved HiSCR; this increased to 60.5% and 62.8% at 24 and 52 weeks of adalimumab treatment, respectively. Significant reductions from baseline in CRP (P < 0.05), skin pain (P < 0.0001), and DLQI (P < 0.0001) were observed at all time points. The results from this PMS study demonstrated that long-term adalimumab treatment is well tolerated and effective in patients with HS in real-world clinical practice in Japan.

Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: 12-week interim analysis of post-marketing surveillance in Japan.

Hidradenitis suppurativa (HS) is a painful chronic skin disease characterized by abscesses, nodules, and tunnels in the skin. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, is approved for the treatment of HS in Europe, the USA, and Japan. This multicenter, open-label, post-marketing, observational study (ClinicalTrials.gov: NCT03894956) evaluated the safety and effectiveness of adalimumab in routine clinical practice in Japan (March 2019-May 2021). Patients with HS were treated with s.c. doses of adalimumab according to the dosage described in the package insert. The primary end-point was safety (data cut-off, December 2020). Secondary end-points assessed effectiveness, including HS Clinical Response (HiSCR), skin pain, Dermatology Life Quality Index (DLQI), and C-reactive protein (CRP). Here, we report 12-week interim effectiveness results. A total of 84 eligible patients from 65 sites were enrolled; 83 patients were included in this analysis. Mean age was 42.0 years, mean body mass index was 26.9 kg/m2 , 78.3% of patients were male, 61.4% had Hurley stage III disease, 39.8% had a disease duration ≥10 years, and 7.2% had a family history of HS. The most common affected sites were the axilla (60.2%), buttocks (59.0%), and the inguinal and femoral regions (47.0%). Mean abscess and inflammatory nodule count was 13.0 (standard deviation, 12.0). Among patients with a comorbidity (57.8%), the most common were diabetes mellitus, hypertension, and chronic kidney disease. No patient reported a serious infection or any safety event of special interest. One patient died from a serious adverse event of cardiac failure unrelated to adalimumab. At week 12, 57.4% of patients achieved HiSCR, and significant reductions from baseline in skin pain, DLQI (both p < 0.0001), and CRP (p = 0.0029) were observed. These results support the administration of adalimumab as a well-tolerated and effective treatment for Japanese patients with HS in real-world clinical practice.

Real-World Postmarketing Study of the Impact of Adalimumab Treatment on Work Productivity and Activity Impairment in Patients with Psoriatic Arthritis.

INTRODUCTION: This study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan. METHODS: This 24-week, single-arm, postmarketing surveillance study (2014-2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates. RESULTS: In the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, - 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7-67.8) and 39.0% (29.4-49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6-93.9), 70.7% (57.3-81.9), and 53.4% (39.9-66.7), respectively. No new safety signals were observed in the safety population (n = 148). CONCLUSION: Adalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02414633. FUNDING: AbbVie GK and Eisai Co., Ltd.

Real-world effectiveness and safety of adalimumab for treatment of ankylosing spondylitis in Japan.

Objective: To evaluate the real-world effectiveness and safety of adalimumab for the treatment of ankylosing spondylitis (AS) in Japan.Methods: All AS patients initiated on adalimumab from 27 October 2010 to 28 May 2015, were enrolled. Patient characteristics at baseline, changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, and adverse drug reactions (ADRs) for 24 weeks from the first adalimumab treatment were evaluated.Results: Of 403 enrolled patients, 396 and 374 comprised the safety and effectiveness analysis sets, respectively. In the safety analysis set, 266/396 (67.2%) were males, with a mean ± standard deviation (SD) age of 46.3 ± 15.6 years and mean ± SD disease duration of 9.8 ± 9.8 years. Of 236 patients examined for human leukocyte antigen (HLA)-B27, 131 (55.5%) were HLA-B27-positive. In the effectiveness analysis set, the mean ± SD BASDAI score was 4.9 ± 2.3 at baseline (n = 292). Overall, 216 patients had BASDAI data pre- and post-baseline. At 24 weeks, 143 patients had BASDAI scores, and the mean ± SD decrease was -2.0 ± 2.6 (p < .0001). Fifteen serious ADRs occurred in 15 (3.79%) patients; 30 (7.58%) ADRs of infections were reported, of which, five (1.26%) were serious.Conclusion: Safety and effectiveness of adalimumab in this postmarketing observational study were similar to that in previous clinical trials.

Correction to: Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

"Newborns, infants, or young children aged 24 months and under who have Down syndrome, and children ≤ 24 months of age without a current hs-CHD if they had experienced persistent respiratory symptoms or regular outpatient treatment due to a respiratory tract infection in previous RSV seasons were also eligible for the study."

Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan.

OBJECTIVE: The aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome. METHODS: In this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged ≤24 months with immunocompromised conditions or Down syndrome (without hemodynamically significant congenital heart disease) receiving palivizumab immunoprophylaxis during two RSV seasons were observed until 30 days after the final palivizumab injection. Safety [adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs)] and effectiveness (frequency, incidence, and duration of hospitalization due to RSV infections) were assessed. RESULTS: Of 304 patients receiving palivizumab, 167 (54.9%) had immunocompromised conditions, and 138 (45.4%) had Down syndrome; 260 (85.5%) completed palivizumab immunoprophylaxis. The annual mean (±standard deviation) number of doses was 5.3 (±2.4) per season. Overall, 220 AEs occurred in 99 patients (32.6%), including 89 SAEs in 53 patients (17.4%). Of these, 33 AEs in 25 patients (8.22%) were considered ADRs, and 13 ADRs in 11 patients (3.62%) were considered SADRs. In four patients, five SADRs (nephroblastoma and asthma in the same patient, septic shock, device-related infection, and drug-induced liver injury) were previously unreported; however, none were considered drug-related. During the observation period, five RSV infections occurred and two patients required hospitalization. CONCLUSION: Palivizumab was generally safe and effective for the prevention of LRI caused by RSV in newborns, infants, and children with immunocompromised conditions or Down syndrome up to the age of 24 months.

Smallpox and season: reanalysis of historical data.

Seasonal variation in smallpox transmission is one of the most pressing ecological questions and is relevant to bioterrorism preparedness. The present study reanalyzed 7 historical datasets which recorded monthly cases or deaths. In addition to time series analyses of reported data, an estimation and spectral analysis of the effective reproduction number at calendar time t, R(t), were made. Meteorological variables were extracted from a report in India from 1890-1921 and compared with smallpox mortality as well as R(t). Annual cycles of smallpox transmission were clearly shown not only in monthly reports but also in the estimates of R(t). Even short-term epidemic data clearly exhibited an annual peak every January. Both mortality and R(t) revealed significant negative association (P < .01) and correlation (P < .01), respectively, with humidity. These findings suggest that smallpox transmission greatly varies with season and is most likely enhanced by dry weather.

[Infectious diseases that people should be informed: a Delphi survey of clinicians engaged in practice of infectious diseases in Japan].

OBJECTIVE: To identify specific infectious diseases about which the Japanese public should be informed. MATERIALS AND METHODS: A Delphi survey was conducted, recruiting 26 physicians who are engaged in clinical practice of infectious diseases and working at designated medical institutions of infectious diseases in Japan. RESULTS: Following HIV/AIDS (first ranked), tuberculosis (second) and influenza (third), 24 diseases in total were identified based on "knowledge, awareness and behavior of inhabitants" or "social and clinico-epidemiological circumstances". Scores for the top three ranked diseases were more than two-folds of those for following diseases. Among the top 10 ranked diseases, 9 were in common with the previous survey result among public health physicians and veterinarians working for governmental agencies. DISCUSSION: Our findings of scores for specific diseases most likely reflect an importance of performing preventions and early diagnoses of severe diseases and promoting prophylaxis for travelers' diseases which tend to be factors for prioritizing infectious diseases among clinicians. The top-scored diseases among clinicians were consistent with those among public health officers, indicating the critical need to inform the public about these diseases. Nevertheless, both clinicians and public health experts have already attempted to promote preventions and/or treatment for these diseases in the previous time, and thus, the previous experience must be critically reviewed and reconsidered for improvements. In future, the similar surveys to ours should target specific subjects of experts and investigate more specific types of infectious diseases. Following such an expert survey, concrete action plans to inform the public about prioritized diseases are also called for.

Lactobacillus nodensis sp. nov., isolated from rice bran.

Gram-positive, rod-shaped, non-motile lactic acid bacteria, strains iz4b-1T, iz4b-2 and iz4c-1, were isolated in an attempt to study the composition of the Lactobacillus flora of Japanese pickles. Analysis of their 16S rRNA gene sequences revealed that the strains clustered in the Lactobacillus alimentarius group, and comparatively high similarities were shown to 'Lactobacillus tucceti' CECT 5920 (97.0 %), Lactobacillus versmoldensis KU-3T (96.4 %) and Lactobacillus nantensis LP33T (94.4 %). DNA-DNA hybridization assays clearly revealed that the isolates represented a novel taxon. The DNA G+C content was 40.6 mol% and the peptidoglycan type was L-Lys-D-Asp. Thus, these isolates represent a novel Lactobacillus species, for which the name Lactobacillus nodensis sp. nov. is proposed. The type strain is iz4b-1T (=DSM 19682T =JCM 14932T).

Synthesis of a newly peptide nucleic acid that contains tertiary amino groups.

A thymine monomer of pyrrolidine-based peptide nucleic acid that contains a tertiary amino group in the backbone has been synthesized for use in the synthesis of novel peptide nucleic acid.