Advances in Therapy

In this 2-week, randomized, crossover study, ophthalmic solutions of nedocromil sodium 2% and olopatadine hydrochloride 0.1% were compared for effectiveness and acceptability in 28 patients with perennial allergic conjunctivitis and previous olopatadine experience. Patients received nedocromil twice daily or olopatadine twice daily for 1 week, then were crossed over to the alternate medication for 1 week. Outcome measures were patient satisfaction (questionnaire), severity of ocular symptoms (daily diary scores), clinical signs (physician assessments), quality of life (questionnaire), and global assessments of effectiveness. Both medications were well accepted. Of the 28 patients, 16 (57.1%) would request a nedocromil prescription, 10 (35.7%) an olopatadine prescription (P =.157); 22 patients (78.6%) would recommend nedocromil to other allergy sufferers, while 18 (64.3%) would recommend olopatadine (P =.480). Light sensitivity scores were significantly lower with nedocromil (P =.0125); other symptom scores were comparable between medications. Both drugs significantly (P< .01) and comparably decreased erythema, conjunctival injection, and overall conjunctival signs from baseline. Comparable improvement also occurred in quality-of-life scores. Both physicians and patients judged nedocromil and olopatadine to be similarly effective in preventing signs and symptoms. Nedocromil sodium 2% is an effective treatment for perennial allergic conjunctivitis. Patients receiving olopatadine can be switched to nedocromil with no loss in efficacy or satisfaction, but with a reduction in cost.

Conventional pharmaceutical interventions for inflammatory bowel disease (IBD) provide limited disease/symptom control and are associated with an increased risk of adverse events (AEs). These limitations increase patient morbidity, medical resource utilization (MRU), and costs. The IQVIA™ Real-World Data Adjudicated Claims–US database was leveraged to identify adult patients (> 18 years) with Crohn’s disease (Crohn’s) or ulcerative colitis (UC), who were new and chronic users (≥ 60 days) of oral corticosteroids (OCS), immunosuppressants (IS), anti-tumor necrosis factor agents (anti-TNF) or combinations thereof. Using aminosalicylate-treated patients as a reference, we compared AE incidence, MRU, and medical costs across drug classes. The analysis included 30,676 patients (Crohn’s: n = 14,528; UC: n  = 16,148). OCS monotherapy was the strongest predictor of any AE occurring [Crohn’s: hazard ratio 1.62 (1.51–1.73); UC: hazard ratio 1.57 (1.49–1.66)]. A similar pattern was observed for severe infection and bone-related conditions. Patients with UC or Crohn’s receiving OCS or IS plus OCS were more likely to have emergency department visits, IBD-related hospitalizations/visits/procedures, and gastrointestinal surgery than were patients receiving other therapies. Annualized total medical costs (pharmacy plus hospital service costs) were greatest for anti-TNF plus IS or anti-TNF therapy in both Crohn’s and UC. Annualized medical service costs (excluding IBD drug costs) were highest for patients initiating OCS-containing therapies [Crohn’s: OCS, $27,041 (24,882–29,200) and OCS plus IS, $23,332 (19,889–26,775); UC: OCS, $19,659 (17,977–21,340)]. Although biologic therapies have higher pharmacy costs, treatment decisions should consider the increased AE risks and long-term MRU costs associated with chronic use of OCS-containing therapies. This study was funded by F. Hoffmann-La Roche Ltd. The journal’s Rapid Service Fee and Open Access publication were paid for by ApotheCom on behalf of Genentech, a member of the Roche group who funded the study.

Hyponatremia is a frequent comorbid condition of patients hospitalized for cirrhosis and a predictor of disease severity and mortality. This study evaluated the healthcare burden of hyponatremia among patients hospitalized for cirrhosis in the real world. Hyponatremic (HN) patients (>-18 years of age) with cirrhosis were identified using the Premier Hospital Database (January 1, 2007 to March 31, 2010) and matched to non-HN patients with cirrhosis using a combination of exact patient characteristics and propensity score matching. Univariate and multivariate statistics were utilized to compare hospital resource utilization, cost, and 30-day hospital re-admission among patient cohorts. The study population included 21,864 subjects (HN 10,932; non-HN 10,932). The hospital length of stay (LOS) (7.63 ± 7.4 vs. 5.89 ± 6.2 days; P < 0.001), hospital cost ($13,842 ± $20,702 vs. $11,140 ± $20,562; P < 0.001), intensive care unit (ICU) LOS (4.58 ± 4.7 vs. 3.59 ± 4.4 days; P < 0.001), and ICU cost ($7,038 ± $7,781 vs. $5,360 ± $7,557; P < 0.001) were greater for the HN cohort, as was the 30-day re-admission rate (all cause: 31.1% vs. 24.8%; P < 0.001; hyponatremia related: 25.1% vs. 11.0%; P < 0.001). Multivariate analysis showed that hyponatremia was associated with a 29.5% increase in hospital LOS, a 26.6% increase in overall hospital cost, a 23.2% increase in S. ICU LOS, and a 28.6% increase in ICU cost. Additionally, hyponatremia was associated with an increased risk of 30-day hospital re-admission (all cause: odds ratio [OR] 1.37; confidence interval [CI] 1.28-1.46; P < 0.001; hyponatremia related: OR 2.68; CI 2.48-2.90; P < 0.001). Hyponatremia in patients with cirrhosis is a predictor of increased hospital resource use and 30-day hospital re-admission, and represents a potential target for intervention to reduce healthcare expenditures for patients hospitalized for cirrhosis.

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

Emerging evidence suggests psoriatic arthritis (PsA) with axial involvement (axPsA) and radiographic axial spondyloarthritis (r-axSpA) may possibly represent distinct disorders, with some differing clinical manifestations, genetic associations, and radiographic findings. Moreover, axPsA and r-axSpA may respond differently to therapies: guselkumab (interleukin [IL]-23p19 subunit inhibitor [i]) and ustekinumab (IL-12/23p40i) demonstrated improvements in axial symptoms in patients with PsA; however, neither risankizumab (IL-23p19i) nor ustekinumab demonstrated efficacy versus placebo in patients with r-axSpA. Current analyses aim to further understand potential molecular distinctions between axPsA and r-axSpA and examine the pharmacodynamic effects of guselkumab in patients with axPsA and those with PsA without axial involvement (non-axPsA). Post hoc analyses utilized biomarker data from blood and serum samples collected from a subset of participants in phase 3 studies of ustekinumab in r-axSpA and guselkumab in PsA (DISCOVER-1 and DISCOVER-2). Participants with axPsA were identified by investigator-verified sacroiliitis (imaging-confirmed) and axial symptoms. HLA mapping, serum cytokine analysis, and whole-blood RNA sequencing were conducted. Relative to r-axSpA, patients with axPsA had a lower prevalence of HLA-B27, HLA-C01, and HLA-C02 alleles and a higher prevalence of HLA-B13, HLA-B38, HLA-B57, HLA-C06, and HLA-C12 alleles. Compared with r-axSpA, patients with axPsA had elevated baseline levels of serum IL-17A and IL-17F cytokines, enrichment of IL-17 and IL-10 pathway-associated genes, and neutrophil gene markers. Across axPsA and non-axPsA cohorts, reductions in cytokine levels and normalization of pathway-associated gene expression with guselkumab treatment were comparable. The differences in HLA genetic associations, serum cytokines, and enrichment scores support the concept that axPsA and r-axSpA may be distinct disorders. The comparable pharmacodynamic effects of guselkumab on cytokine levels and pathway-associated genes observed in patients with axPsA and non-axPsA are consistent with demonstrated clinical improvements across PsA cohorts. These findings contribute to the understanding of potential genetic and molecular distinctions between axPsA and r-axSpA. ClinicalTrials.gov identifiers, NCT03162796, NCT0315828, NCT02437162, and NCT02438787.

For over 20 years, the World Health Assembly has recognized diabetes (type 1 and type 2) as a serious threat to national health and economic development and called for action regarding its prevention and control. However, the prevalence of type 2 diabetes continues to rise despite a significant percentage of cases being preventable. Furthermore, data suggest that in many patients diagnosed with type 2 diabetes, glycated hemoglobin (HbA1c) levels remain above the agreed international and national target levels, despite the availability of numerous antihyperglycemic agents, the best intentions of both patient and physician, and the support of the wider healthcare team. Part I of this two-part review considers evidence that seems to suggest there is a knowledge, attitude, and practice (KAP) gap in type 2 diabetes, and that although theoretical knowledge of how type 2 diabetes should be managed exists, the attitude of patients and healthcare professionals may influence the practicalities of implementing life-enhancing changes for patients living day-to-day with the condition. Here, we consider why there may be a KAP gap, how type 2 diabetes is currently being assessed and managed, and whether these current management approaches remain valid in the light of recent studies evaluating the impact of lowering current target HbA1c levels. This article also explores how encouraging patients to self-manage their disease, as well as engaging all stakeholders in the necessary behavioral changes, can positively influence the long-term treatment outcomes of patients with type 2 diabetes.

Crohn’s disease (CD) is a chronic and progressive disease in which the long-term management is important. This study sought to assess treatment persistence and dose escalation in the maintenance phase with adalimumab (ADA) or infliximab (IFX) in a Japanese real-world setting. A retrospective analysis was conducted using the Japan Medical Data Center database. CD patients with either ADA or IFX prescriptions between January 2012 and February 2015 were included. Outcomes of interest were (1) failure in the induction phase (defined as switch or discontinuation) and (2) persistence in the maintenance phase (defined as the absence of switch or discontinuation over 12 months since maintenance initiation). Overall, 133 patients (53 ADA; 80 IFX) were included. Of them, treatment failed in 26 patients (19.6%) in the induction phase. During the induction phase, there was a trend towards fewer treatment failures with ADA than IFX (88.7% vs. 75.0%; p = 0.051). Of those who completed induction, 64 patients (33 ADA; 31 IFX) had at least 12 months of valid insurance enrolment after the initiation of maintenance and 13 (5 ADA; 8 IFX) had either switch or discontinuation within 12 months after the initiation of maintenance. Probabilities of switch or discontinuation over 12 months after the maintenance date were 15.2% and 20.9% for ADA and IFX groups, respectively (p-log rank = 0.7764). Japanese patients have a high primary response to anti-tumor necrosis factor therapy in the real-world setting, in line with the results of clinical trials. This initial therapeutic advantage can be lost during the maintenance phase, leading to dose escalation, treatment switch, or discontinuation. This study suggests that those events occurred in comparable proportions of patients treated with either ADA or IFX. However, these findings should be considered with caution given the retrospective nature and small size of the study. Abbvie GK, Tokyo, Japan.

Etrolizumab is a next-generation anti-integrin with dual action that targets two pathways of inflammation in the gut. A robust phase 3 clinical program in ulcerative colitis (UC) and Crohn’s disease is ongoing and will evaluate the efficacy and safety of etrolizumab in well-defined patient populations in rigorous trials that include direct head-to-head comparisons against approved anti-tumor necrosis factor alpha agents (anti-TNF). The etrolizumab phase 3 clinical program consists of six randomized controlled trials (RCTs; UC: HIBISCUS I and II, GARDENIA, LAUREL, HICKORY; Crohn’s disease: BERGAMOT) and two open-label extension trials (OLEs; UC: COTTONWOOD; Crohn’s disease: JUNIPER) evaluating patients with moderately to severely active UC or Crohn’s disease. In the UC RCTs, patients are randomly assigned according to each protocol to receive etrolizumab, adalimumab, infliximab, or placebo. In BERGAMOT, patients are randomly assigned to receive etrolizumab 105 mg, etrolizumab 210 mg, or placebo. The primary outcomes for the UC RCTs are Mayo Clinic score-based clinical response, remission, and clinical remission; for BERGAMOT, the co-primary outcomes are clinical remission (based on abdominal pain and stool frequency) and endoscopic improvement (based on the Simple Endoscopic Score for Crohn’s disease). The OLEs will primarily assess long-term efficacy and safety. Secondary and exploratory endpoints include endoscopy, histology, quality of life, and biomarkers at various timepoints. The etrolizumab phase 3 clinical program is the largest and most comprehensive in inflammatory bowel disease, enrolling more than 3000 patients. The program explores both induction and maintenance regimens. HIBISCUS I and II and GARDENIA are among the first head-to-head trials in UC against an anti-TNF and are the first registrational trials making that comparison. This program will also help address unanswered clinical questions on evaluation of treatment effects and treatment selection across a range of patients with varying treatment histories using an extensive repository of patient samples and data. ClinicalTrials.gov: HIBISCUS I (NCT02163759), HIBISCUS II (NCT02171429), GARDENIA (NCT02136069), LAUREL (NCT02165215), HICKORY (NCT02100696), COTTONWOOD (NCT02118584), BERGAMOT (NCT02394028), JUNIPER (NCT02403323).