AIM:To compare the use of vildagliptin and sulfonylurea with or without metformin in Indian Muslim patients with type 2 diabetes mellitus, fasting during Ramadan. METHODS:This was a 4-wk, multicenter, non-interventional, open-label, observational study. Incidence of hypoglycemic events (HEs), adverse events, and changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, postprandial plasma glucose and body weight were measured pre-and post-Ramadan. RESULTS:Totally, 97 patients were recruited and all completed the study (vildagliptin group, n = 55; sulfonylurea group, n = 42). HEs were reported in low Key words: Dipeptidyl-peptidase 4 inhibitors; Fasting hypoglycemia; Sulfonylurea; Type 2 diabetes mellitus; Vildagliptin Core tip: Management of glycemic control in diabetes patients fasting during Ramadan has been recognized as a critically important health challenge worldwide. India has the world's second largest diabetes population and caters large Muslim community; however, there is limited data available exploring the effect of treatments

Background Ankylosing spondylitis (AS) is a chronic inflammatory condition with pain, stiffness and fatigue reported as the most troubling symptoms. Early and sustained relief of these symptoms is essential for effective management. Secukinumab provided sustained relief from pain and fatigue in AS patients over 2 years in the MEASURE 2 study. We report the effect of subcutaneous secukinumab 150 mg on key clinical symptoms (pain, morning stiffness and fatigue) in AS patients over 208 weeks in MEASURE 2. Methods This post-hoc analysis of MEASURE 2 assessed mean change from baseline to Week 208 in total and nocturnal back pain scores (by VAS [0-100]; ASAS outcome component), overall level of spinal pain (neck, back or hip) from BASDAI scores, and morning stiffness (overall level; mean of question 5 and 6 of BASDAI score). Additionally, the SF-36 physical component summary score, overall level of fatigue (BASDAI question 1), FACIT-Fatigue score and patients meeting minimal clinically important difference (MCID) criteria across multiple clinical domains were assessed. Data are shown for patients originally randomised to secukinumab 150 mg and placebo. Data are reported as observed for the overall population and by prior TNF inhibitor (TNFi) therapy status (naive vs inadequate response [IR]). Results Baseline characteristics were comparable across secukinumab 150 mg (N = 72) and placebo (N = 74) groups; total mean back pain score was 67.7±17.79, nocturnal back pain score was 64.9±19.58 and morning stiffness was 6.5±2.11. Secukinumab 150 mg-treated patients reported rapid and early reductions in pain scores by Week 4, which were sustained through Week 208 (Table 1). Improvements with secukinumab 150 mg were reported for all key clinical symptoms by Week 4, which were sustained at Week 208. A higher proportion of secukinumab 150 mg-treated patients met MCID criteria at Week 16 vs placebo across multiple clinical domains, which was sustained or further improved through Week 208. Improvements were observed in TNFi-naive and -IR patients, with a greater magnitude of improvement in TNFi-naive patients. Conclusion Secukinumab 150 mg was associated with rapid and clinically meaningful improvements in total and nocturnal back pain, morning stiffness and fatigue, with improvements sustained over 4 years of treatment. Disclosures H. Marzo-Ortega: Consultancies; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Member of speakers’ bureau; AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, UCB. Grants/research support; Janssen, Novartis. C. Miceli-Richard: Consultancies; Pfizer, Roche, UCB, Wyeth, Merck. Member of speakers’ bureau; Abbott, Bristol-Myers Squibb, Merck, Pfizer, Roche, Schering-Plough, Wyeth. Grants/research support; AbbVie, Bristol-Myers Squibb, Novartis, Merck, Pfizer, Wyeth. S. Gill: Consultancies; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. Other; AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Amgen, Sanofi-Genzyme. M. Magery: Consultancies; Eli Lilly, Novartis. Grants/research support; AbbVie, UCB, Amgen. P.G.P. Machado: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Shete: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. J. Wang: Other; Employee of Novartis. S. Rohrer: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Deodhar: Consultancies; AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Galapagos, Janssen, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, GSK, Novartis, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, UCB.

IMPORTANCE Approximately one-quarter of the global population have latent tuberculosis infection (LTBI), and tuberculosis (TB) is accountable for more than 1.5 million deaths annually. Methotrexate, cyclosporine, and tumor necrosis factor inhibitors may be associated with increased risk of TB and LTBI reactivation, although data are limited on the risks of TB with use of newer biologics. OBJECTIVE To assess the association of secukinumab with reporting of active TB development, TB reactivation, and LTBI activation as an adverse event (AE) in patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis. DESIGN, SETTING, AND PARTICIPANTS This qualitative study pooled data from 28 clinical trials of secukinumab used in psoriasis (17 phase 3 or 3b and 2 phase 4 trials), psoriatic arthritis (5 phase 3 trials), and ankylosing spondylitis (4 phase 3 trials). A search of the Novartis Secukinumab Compound Pool Database was conducted for the 28 trials. All trial participants who had received at least 1 approved subcutaneous dose of secukinumab (150 mg or 300 mg) were included. Before randomization in these trials, patients underwent screening for TB. Patients with active TB were excluded, and patients with LTBI were treated according to local guidelines. Data were analyzed from the start of treatment in the individual studies through December 25, 2018. MAIN OUTCOMES AND MEASURES Reporting of active TB or LTBI as an AE over a 5-year period using exposure-adjusted incidence rates (EAIR; incidence rates per 100 patient-years). RESULTS A total of 12 319 patients were included, of whom 8819 patients had psoriasis (71.6%; 5930 men [67.2%]; mean [SD] age, of 44.9 [13.5] years), 2523 had psoriatic arthritis (20.5%; 1323 women [52.4%]; mean [SD] age, 48.8 [12.1] years), and 977 had ankylosing spondylitis (7.3%; 658 men [67.3%]; mean [SD] age, 42.3 [11.9] years). In the total population, 684 patients (5.6%) had tested positive for LTBI at screening. Over 5 years, LTBI as an AE during secukinumab treatment was reported in 13 patients (0.1% of 12 319). Of these 13 patients, 6 had a prior positive LTBI test result, and 7 were newly diagnosed as having LTBI. Four of the 7 patients had psoriasis (EAIR, 0.03; 95% CI, 0.01-0.07), 1 had psoriatic arthritis (EAIR, 0.02; 95% CI, 0.00-0.11), and 2 had ankylosing spondylitis (EAIR, 0.08; 95% CI, 0.01-0.28). No cases of active TB were reported. CONCLUSIONS AND RELEVANCE This study found that LTBI reported as an AE after secukinumab treatment was uncommon and appeared to support the use of secukinumab in chronic systemic inflammatory conditions.

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was < 0.2/100 patient-years, the incidence of malignancy was ≤ 1/100 patient-years, and the incidence of major adverse cardiovascular events was < 0.7/100 patient-years, with no apparent increases over time. Secukinumab demonstrated a favourable safety profile for up to 5 years of treatment across the 3 indications, and no new safety signals were identified.

Background To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. Methods The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. Results Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. Conclusions Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients. Trial registration ClinicalTrials.gov, NCT02696031. Registered on 02 March 2016