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Introduction: This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). Methods: Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months' (primary) or 12/18 months' (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months' post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). Results: The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months' GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months' GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. Conclusion: Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. Clinical Trial Registration: ClinicalTrials.gov, NCT02959177 and NCT02959190. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of galcanezumab as a preventive treatment in Japanese patients with episodic migraine was demonstrated in a phase 2, randomized, placebo-controlled trial (conducted December 2016–January 2019). This post hoc analysis assessed the consistency of galcanezumab efficacy through the monthly dosing interval. Methods: Patients with 4–14 migraine headache days/month were randomized (2:1:1, stratified by baseline migraine frequency) to subcutaneous placebo (n = 230), 120-mg galcanezumab (with 240-mg loading dose; n = 115) or 240-mg galcanezumab (n = 114) once monthly for 6 months. Outcomes included change from baseline in weekly migraine headache days, proportion of patients with migraine headache on each day, and proportion of patients with worsening migraine headache days during each month ([average of weeks 3–4] − [average of weeks 1–2] > 0). Results: In the 120-mg (approved dose) galcanezumab group, mean change from baseline in weekly migraine headache days was consistent and significantly greater (p < 0.05) than placebo for weeks 1–4; efficacy was consistent when averaged across months 1–6 and in most individual months. Averaged across months 1–6, the proportion of patients with migraine headache was significantly lower with galcanezumab than placebo on every day in both dose groups and was not significantly different between days 2 and 28 with 120-mg galcanezumab (p = 0.161). Within each month, the proportion of patients with migraine headache was generally consistent from days 2–28. The proportion of patients with worsening during the dosing interval did not significantly exceed 50% in any group during any month. Conclusions: This post hoc analysis supports the consistency of efficacy of galcanezumab across 6 months of treatment and suggests that wearing-off within the dosing interval does not occur on a population level in Japanese patients with episodic migraine. Trial Registration: ClinicalTrials.gov identifier, NCT02959177. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal antiinflammatory drugs (NSAIDs) are commonly used for pain disorders such as low back pain and exist in multiple formulations; however, no systemically acting transdermal formulations are available for low back pain. Transdermal formulations can be safely administered even to patients with trouble swallowing or at risk of aspiration, and without regard to the effect of food on drug absorption. Unlike locally acting formulations, systemically acting transdermal formulations need not be applied at the target site, so dosing is simple and the burden is not on one area of the skin. A patch with the systemically acting NSAID diclofenac sodium is approved in Japan for treatment of cancer-related pain, and we hypothesized that it would be useful for controlling low back pain. Methods: This randomized, double-blind, placebo-controlled study aimed to evaluate the efficacy and safety of diclofenac sodium patch in Japanese patients with low back pain. Eligible patients were randomized to receive diclofenac sodium patch 75 mg or 150 mg or placebo once daily for 2 weeks. The primary endpoint was pain intensity assessed on a visual analog scale (VAS). Results: Primary analysis of the primary endpoint showed that both doses of the diclofenac sodium patch (150 mg and 75 mg) were superior to placebo in terms of absolute change from baseline in mean 3-day VAS score after 2 weeks' treatment; the mean difference between the active and placebo treatments in this variable was −5.67 [95% confidence interval (CI) −9.34 to −2.00] mm in the 150 mg group and −5.68 (95% CI −9.34 to −2.01) mm in the 75 mg group. Most adverse events were mild. No serious adverse events occurred. Conclusion: In Japanese patients, diclofenac sodium patch is effective for the relief of low back pain and is well tolerated. Trial Registration: JPRN number, JPRN-JapicCTI-205134. [ABSTRACT FROM AUTHOR]

Introduction: Bimekizumab treatment resulted in improved clinical outcomes in patients with moderate-to-severe plaque psoriasis in BE VIVID, a 52-week, phase 3, randomized, ustekinumab and placebo-controlled study. We present data from the BE VIVID Japan patient subpopulation. Methods: Globally, patients were randomized to receive bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16, then bimekizumab 320 mg Q4W). Efficacy endpoints included week 16 Psoriasis Area and Severity Index (PASI) 90 and Investigator's Global Assessment (IGA) 0/1, and other outcomes [PASI 100, PASI 75, IGA 0, Dermatology Life Quality Index (DLQI) 0/1, absolute PASI, scalp IGA, Psoriasis Symptoms and Impacts Measure (P-SIM) responses]. Safety analyses were conducted. Results: There were 108 Japanese randomized patients (bimekizumab: 62; ustekinumab: 29; placebo: 17). At week 16, bimekizumab-treated patients had a higher clinical response versus ustekinumab and placebo (PASI 90: 85.5% versus 51.7% and 5.9%; IGA 0/1: 82.3% versus 48.3% and 0.0%). Over 52 weeks, improved clinical response was maintained with bimekizumab, including patients switching from placebo at week 16. Overall, the safety profile in Japanese patients was consistent with that observed in the global population. Conclusion: Bimekizumab resulted in improved clinical response versus ustekinumab and placebo, and was well-tolerated in Japanese patients. Trial registration: NCT03370133. [ABSTRACT FROM AUTHOR]

Introduction: Galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, is a preventive migraine treatment. In global, randomized, placebo-controlled trials, galcanezumab reduced migraine headache severity and the frequency of migraine headaches associated with nausea and/or vomiting, photophobia and phonophobia, prodromal symptoms, or aura. We report secondary analyses from a Japanese phase 2 trial that assessed the effect of galcanezumab on migraine headache severity, frequency of migraine-associated symptoms, and frequency of migraine headaches during menstrual periods in Japanese patients with episodic migraine. Methods: Adults with migraine (International Classification of Headache Disorders, 3rd edition; 4–14 migraine headache days/month) were randomized (2:1:1) to a monthly placebo (n = 230), 120 mg galcanezumab (240 mg loading dose; n = 115), or 240 mg galcanezumab (n = 114) for 6 months (double-blind). Patients recorded migraine headache days, severity, and symptoms in an electronic diary. Changes from baseline were analyzed (mixed model for repeated measures). Results: Both galcanezumab doses significantly reduced the number of monthly moderate-to-severe and severe migraine headache days compared with placebo, overall (difference in least-squares mean change from baseline, 120 mg/240 mg versus placebo: moderate-to-severe, −1.9/−1.8 days; severe: −0.4/−0.4 days) and in each month; mean severity score was significantly reduced in the 240 mg group. Both galcanezumab doses significantly reduced the number of migraine headache days with nausea/vomiting (−1.1/−1.0 days), photophobia/phonophobia (−2.3/−1.7 days), prodromal symptoms (−0.7/−0.8 days), and aura (−0.7/−0.7 days). In most cases, the proportion of migraine headache days with these symptoms was reduced by galcanezumab. Both galcanezumab doses reduced the number of migraine headache days occurring during menstrual periods (n = 269; −0.8/−0.9 days). Conclusion: Once-monthly galcanezumab significantly reduced the frequency of migraine headache days with moderate-to-severe or severe headache, migraine headache days with migraine-associated symptoms, and migraine headache days during menstrual periods in Japanese patients with episodic migraine, consistent with results from global studies. Trial Registration: ClinicalTrials.gov (NCT02959177). [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor approved in Japan and the European Union for the treatment of atopic dermatitis (AD). The aim of this study is to report pooled safety data for baricitinib in the Japanese subpopulation of the clinical development program in moderate-to-severe AD. Methods: This analysis included participant-level safety data from five double-blind, randomized clinical studies and one double-blind, randomized, long-term extension study, reported in three datasets for the Japanese subpopulation: (1) placebo-controlled, (2) baricitinib 2 mg and 4 mg extended ("2-mg—4-mg extended"), and (3) all baricitinib doses ("All-bari-AD"). The data cutoff was 13 December 2019. Safety outcomes included treatment-emergent adverse events, adverse events of special interest, and abnormal laboratory changes. Proportions of participants with events and incidence rates were calculated. Results: Data were collected for 341 participants from Japan who received baricitinib for 371.7 participant-years (median duration 371.0 days). In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. No gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with exposure up to 2 years in the All-bari-AD dataset. There were no deaths in the Japanese subpopulation. Conclusions: This integrated safety analysis in the subpopulation of Japanese participants is consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe AD. Clinicaltrials.gov identifiers: NCT02576938, NCT03334396, NCT03334422, NCT03428100, NCT03733301, and NCT03334435. [ABSTRACT FROM AUTHOR]