Five-year Safety Data From OPUS, a European Observational Safety Registry for Adults With Ulcerative Colitis Treated With Originator Infliximab [Remicade®] or Conventional Therapy.

Background And Aims: The Observational Postmarketing Ulcerative colitis Study [OPUS] was conducted to obtain the first long-term [5 years] safety data assessing treatment with originator infliximab versus conventional therapies in patients with ulcerative colitis [UC] in real-world clinical practice.

Methods: The OPUS registry was a prospective, non-randomised, observational study that measured adverse events in nine prespecified categories of interest in UC patients whose treatment with either originator infliximab or conventional therapy [defined as initiation or dose-increase of corticosteroids and/or immunosuppressants] was determined by their treating physician.

Results: Data for 2239 patients were available: N = 1180 enrolled to conventional therapy [including N = 296 who switched to originator infliximab during follow-up] and N = 1059 enrolled to originator infliximab.

A randomized, clinical trial to assess the relative efficacy and tolerability of two doses of etoricoxib versus naproxen in patients with ankylosing spondylitis.

Background: This study evaluated two doses of etoricoxib (60 and 90 mg) vs. naproxen 1000 mg in subjects with ankylosing spondylitis (AS).

Methods: This was a 2-part, double-blind, active comparator-controlled non-inferiority study in subjects ≥18 years of age with AS.

Effectiveness of Elbasvir and Grazoprevir Combination, With or Without Ribavirin, for Treatment-Experienced Patients With Chronic Hepatitis C Infection.

Background & Aims: Patients infected with hepatitis C virus (HCV) genotype 1, 4, or 6, with or without cirrhosis, previously treated with peg-interferon and ribavirin, are a challenge to treat. We performed a phase 3 randomized controlled open-label trial to assess the effects of 12 or 16 weeks of treatment with once-daily elbasvir (an HCV NS5A inhibitor, 50 mg) and grazoprevir (an HCV NS3/4A protease inhibitor, 100 mg), in a fixed-dose combination tablet, with or without twice-daily ribavirin, in this patient population.

Methods: We analyzed data from 420 patients (35% with cirrhosis, 64% with a null or partial response to peg-interferon and ribavirin) who were randomly assigned (1:1:1:1) to groups given elbasvir and grazoprevir once daily, with or without twice-daily ribavirin, for 12 or 16 weeks, at 65 study centers in 15 countries in Europe, Asia, and Central and North America.

Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), in the treatment of Rheumatoid Arthritis in a double-blind, randomized controlled trial.

Background: Treatment with non-steroidal anti-inflammatory drugs (NSAID) is a common component of treatment regimens for rheumatoid arthritis (RA). Etoricoxib is a COX-2 selective NSAID that has demonstrated efficacy in the treatment of RA at a dose of 90 mg. The current study further evaluated the efficacy of etoricoxib 60 mg and 90 mg in RA patients with active disease.

CXCR2 Antagonist MK-7123. A Phase 2 Proof-of-Concept Trial for Chronic Obstructive Pulmonary Disease.

Rationale: An antagonist (MK-7123) of the cytokine receptor CXCR2 reduces neutrophil chemotaxis and thus may alleviate airway inflammation in chronic obstructive pulmonary disease (COPD).

Objectives: To assess the efficacy, safety, and tolerability of three dose levels of MK-7123, compared with placebo, in patients with moderate to severe COPD.

Methods: This 6-month, double-blind study randomized patients with moderate to severe COPD (already on standard therapy) to daily MK-7123 at 10, 30, or 50 mg or placebo.

Humoral immunity and delayed-type hypersensitivity in healthy subjects treated for 30 days with MK-7123, a selective CXCR2 antagonist.

Antagonism of the chemokine receptor CXCR2 inhibits neutrophil trafficking and may thus be therapeutic in patients with chronic obstructive pulmonary disease and other lung disorders in which there is substantial infiltration by neutrophils. Here, we report the findings from a randomized, placebo-controlled, double-blind clinical trial of the small-molecule CXCR2 antagonist MK-7123 (formerly SCH 527123) that evaluated potential downstream effects of CXCR2 antagonism on immunogenic competency (B cell antibody response) in the adaptive immune system and delayed-type hypersensitivity (DTH) in healthy subjects (ages 34-65 years) dosed once daily for 30 days either with 30 mg MK-7123 (n=24) or placebo (n=7). Eligible subjects were seronegative for anti-hepatitis A virus (HAV) immunoglobulin G (IgG) and positive for DTH response to intradermal injection of Candida albicans antigen at screening.

Safety of mometasone furoate nasal spray in the treatment of nasal polyps in children.

Background: Mometasone furoate nasal spray (MFNS) improves nasal symptoms and reduces polyp size in adults with nasal polyposis. This 4-month, multinational, randomized, double-blind study was conducted to assess the safety of MFNS in pediatric subjects aged 6-17 yr.

Methods: Subjects aged 6-11 yr with bilateral nasal polyps received MFNS 100 μg once or twice daily or placebo; those aged 12-17 yr received MFNS 200 μg once or twice daily or placebo.

Effects of inhaled mometasone furoate on growth velocity and adrenal function: a placebo-controlled trial in children 4-9 years old with mild persistent asthma.

Objective: To assess the effects of long-term mometasone furoate delivered via a dry powder inhaler (MF-DPI) on growth velocity and hypothalamic-pituitary-adrenal axis function in children with asthma.

Study Design: Children aged 4-9 years with asthma (n = 187) were randomized to MF-DPI 100 μg (delivered dose; actuated dose is 110 μg) once daily in the morning (QD AM), 100 μg twice daily (BID), 200 μg QD AM, or placebo for 52 weeks followed by a 3-month follow-up period. The primary outcome was growth velocity calculated from stadiometric heights recorded at each visit.

One-year treatment with mometasone furoate in chronic obstructive pulmonary disease.

Many patients with chronic obstructive pulmonary disease (COPD) are treated with twice daily (BID) inhaled corticosteroids (ICS). This study evaluated whether daily PM mometasone furoate administered via a dry powder inhaler (MF-DPI) was equally effective compared to twice daily dosing.In a 52-week, randomized, double-blind, placebo-controlled study, 911 subjects with moderate-to-severe COPD managed without ICS received MF-DPI 800 microg QD PM, MF-DPI 400 microg BID, or placebo.

Onset of symptomatic effect of mometasone furoate nasal spray in the treatment of nasal polyposis.

Background: The efficacy of the intranasal corticosteroid mometasone furoate nasal spray (MFNS) for treatment of nasal polyposis was demonstrated in 2 large clinical trials.

Objective: To evaluate the onset of MFNS symptomatic effect, data from the 2 trials were pooled and analyzed to determine the first day subjects experienced significant symptom relief.

Methods: Subjects with nasal polyposis randomized to MFNS 200 microg twice daily or placebo scored symptoms on a 3-point scale (0 = none; 3 = severe) and measured peak nasal inspiratory flow immediately before the morning dose.

Challenge of multiple co-primary endpoints: a new approach.

There are many disorders where regulatory agencies have required a new treatment to demonstrate efficacy on multiple co-primary endpoints, all significant at the one-sided 2.5 per cent level, before accepting the treatment's effect for the disorder. This requirement, rooted in the intersection-union (IU) test, has led many researchers to increase the study sample size to make up for the reduction in the statistical power at the study level.

Efficacy and safety of mometasone furoate nasal spray in nasal polyposis.

Background: Studies have suggested that topical corticosteroids are effective in the treatment of nasal polyps; however, this has yet to be confirmed in a large, robust clinical trial.

Objective: To evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) for nasal polyposis.

Methods: A total of 354 subjects with bilateral nasal polyps and clinically significant congestion/obstruction participated in this multinational, randomized, double-blind, placebo-controlled study.

Comparative effects of desloratadine versus montelukast on asthma symptoms and use of beta 2-agonists in patients with seasonal allergic rhinitis and asthma.

Background: Asthma and seasonal allergic rhinitis (SAR) are recognized as manifestations of a single airway disease. Desloratadine has demonstrated efficacy in treating SAR symptoms, including nasal obstruction.

Methods: Safety and efficacy of desloratadine and montelukast each were assessed in a double-blind, placebo-controlled trial of patients with SAR and symptoms of asthma, who were assigned randomly to once-daily treatment with desloratadine 5 mg, montelukast 10 mg, or placebo for 4 weeks.