Bryan L. Love

Regulatory and clinical considerations for biosimilar oncology drugs

Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

Urate-lowering therapy for gout: focus on febuxostat.

Gout is a common, painful, and often debilitating rheumatologic disorder that remains one of the few arthritic conditions that can be diagnosed with certainty and cured with appropriate therapy. Allopurinol is the most frequently prescribed agent for gout in the United States. Unfortunately, most patients treated with allopurinol do not achieve target serum uric acid (sUA) levels, possibly due to a perceived intolerability to allopurinol in doses above 300 mg and the need for reduced doses in patients with renal insufficiency. Febuxostat, an orally administered, nonpurine inhibitor of xanthine oxidase, was recently approved by the U.S. Food and Drug administration for chronic management of hyperuricemia in patients with gout. Patients treated with febuxostat achieve rapid and substantial reductions in sUA levels. Compared with allopurinol‐treated patients, patients receiving febuxostat 80 mg/day were more likely to achieve sUA concentrations less than 6 mg/dl. In long‐term studies (up to 5 yrs), febuxostat demonstrated sustained reductions in sUA levels, nearly complete elimination of gout flares, and a frequency of adverse effects comparable to allopurinol. The most commonly reported adverse effects were liver function abnormalities, rash, nausea, and arthralgias. The recommended starting dose of febuxostat is 40 mg/day, which may be increased to 80 mg/day after 2 weeks if patients do not achieve sUA levels less than 6 mg/dl. Dosage adjustment in mild‐to‐moderate renal insufficiency is unnecessary; however, data are lacking on the safety of febuxostat in patients with severe renal impairment. Although more costly than allopurinol, febuxostat appears to be an acceptable alternative for the treatment of gout and hyperuricemia, and may be advantageous in patients with renal impairment, intolerance to allopurinol, or the inability to attain sUA levels less than 6 mg/dl despite adequate therapy with available agents.

Linaclotide: A novel agent for chronic constipation and irritable bowel syndrome

PURPOSE The pharmacology, pharmaco-kinetics, and clinical efficacy and safety of linaclotide in the management of chronic constipation (CC) and constipation-predominant irritable bowel syndrome (IBS-C) are reviewed. SUMMARY Linaclotide (Linzess, Forest Pharmaceuticals) is a 14-amino acid peptide indicated for the treatment of adults with CC and IBS-C. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation. Linaclotide is approved by the Food and Drug Administration (FDA) for oral once-daily administration at doses of 145 μg for CC and 290 μg for IBS-C. In placebo-controlled Phase III clinical trials, linaclotide significantly increased weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with CC. In patients with IBS-C, linaclotide was demonstrated to be effective in meeting FDA-recommended endpoints such as reductions of at least 30% from baseline in abdominal pain scores and CSBM frequency. The most common adverse effect of linaclotide is diarrhea, which was reported in 16-20% of clinical trial participants. CONCLUSION Linaclotide is an important advance in the treatment of CC and IBS-C, with a novel mechanism of action resulting in accelerated intestinal transit. In clinical trials, linaclotide demonstrated efficacy relative to placebo for treatment of both CC and IBS-C. Linaclotides adverse effects are generally mild and confined to the gastrointestinal tract.

Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: Joint opinion of the GI/liver/nutrition and infectious diseases practice and research networks of the American College of Clinical Pharmacy

The objective of this opinion paper was to identify and describe potential clinical pharmacists’ services for the prevention and management of patients infected with the hepatitis C virus (HCV). The goals of this paper are to guide the establishment and development of pharmacy services for patients infected with HCV and to highlight HCV research and educational opportunities. Recommendations were based on the following: a review of published data on clinical pharmacist involvement in the treatment and management of HCV‐infected patients; a consensus of clinical pharmacists who provide direct patient care to HCV‐infected patients and practice in different pharmacy models, including community‐based and academic settings; and a review of published guidelines and literature focusing on the treatment and management of HCV infections. The recommendations provided in this opinion paper define the areas of clinical pharmacist involvement and clinical pharmacy practice in the treatment and management of patients with HCV. Clinical pharmacists can promote preventive measures and education about reducing HCV transmission, improve medication adherence, assist in monitoring clinical and adverse effects, recommend treatment strategies to minimize adverse effects and drug interactions, and facilitate medication acquisition and logistics that positively improve patient outcomes and reduce the health care system costs.

Development of a Reliable, Valid Annual Skills Mastery Assessment Examination

Objective. To develop a methodology for a reliable, valid annual skills mastery assessment examination to provide formative student feedback, inform curricular review, and comply with the Accreditation Council for Pharmacy Education (ACPE) Standards 2007. Design. A sample of program-level ability-based outcomes skills were chosen for the examination. Test items were written, underwent quality control, and were scored for level of difficulty. Versions of the examination for first-, second-, third-, and fourth-year pharmacy students were developed and administered, the results were analyzed, reliability and validity were evaluated, and reports were generated. Item-writing guidelines, quality control procedures, and examination production steps were codified to create a criterion-referenced examination. Students and faculty advisors received detailed score reports and results were used to guide student performance and stimulate a review of curricular outcomes. Assessment. Content, criterion, and construct validity were analyzed as defined in the literature for the intended use of this assessment tool. Data suggest the Annual Skills Mastery Assessment (ASMA) examination is both reliable and valid. Students and faculty members were surveyed regarding the usefulness of the examination. Results indicate general satisfaction with the assessment program. Conclusion. A reasonably reliable, reasonably valid multiple-choice annual skills mastery assessment for selected outcomes statements providing formative feedback and informed curricular review was developed.

Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists

Hepatitis C virus (HCV) is the most common blood‐borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one‐time HCV screening for all patients born between 1945 and 1965, in addition to risk factor–based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct‐acting antivirals. The approval of ledipasvir‐sofosbuvir, ombitasvir‐paritaprevir‐ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment‐naïve and treatment‐experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance‐associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes.

Extended-Release Mesalamine Granules for Ulcerative Colitis

OBJECTIVE: To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). DATA SOURCES: Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. DATA SYNTHESIS: The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. CONCLUSIONS: Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

Systematic Approach to Pharmacovigilance beyond the Limits: The SouthernNetwork on Adverse Reactions (SONAR) Projects

As of 2013, the Southern Network on Adverse Reactions (SONAR) team described 50 significant adverse drug reactions (sADRs) associated with FDA approved drugs. The team also investigates policy issues surrounding pharmacovigilance. Herein we describe the systematic approach to pharmacovigilance taken by the Southern Network on Adverse Reactions and discuss major findings from the group. By 2015, the team hopes to have identified 20 additional sADRs focusing on biologics, biosimilars, and biobetters. The ultimate goal of SONAR is to decrease the timescale between ADR detection and the dissemination of information regarding the sADR

Topiramate: Safety and Efficacy of its Use in the Prevention and Treatment of Migraine

Migraine headaches are typically episodic in nature and may affect nearly 10% of the population. In addition to treatment, prevention of subsequent episodes or progression to a chronic migraine state is an important therapeutic area. Topiramate is a centrally acting medication approved for both the prevention of seizures and migraine headache. At this time, the exact mechanism of how topiramate assists in migraine prevention is unknown. Several large randomized, controlled trials have aided in establishing topiramates role in migraine prevention. Despite a favorable pharmacokinetic and adverse effect profile established in clinical trials, several additional studies, case reports and toxicology reports have demonstrated topiramate as a cause of cognitive and behavioural changes. The use of topiramate in migraine prevention can improve a patients quality of life and is a cost-effective option for migraine prevention.

The changing landscape of adverse drug events associated with chronic hepatitis C virus therapy

Treatment of chronic hepatitis C virus (HCV) therapy has rapidly changed since the approval of IFN in the 1990s. Early treatment brought about significant and therapy limiting adverse drug events (ADEs) such as anemia. Since the direct-acting antivirals were first approved in 2011 and then advanced in 2013, treatment-related ADEs and therapy discontinuations have rapidly decreased, while sustained virologic response rates have significantly increased. As the market for treating chronic HCV therapy has changed, so too has the ADE profile clinicians may need to manage.