Lisa M. Lundquist

Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis.

Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type I cytokine receptors family and γ-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinbs mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials.

A comparison of students' self-assessments with faculty evaluations of their communication skills.

Objective. To compare students’ self-assessment of their communication skills with faculty members’ formal evaluation of their skills in a therapeutics course. Methods. Over a 3-year period, faculty members evaluated second-year pharmacy students’ communication skills as part of a requirement in a therapeutics course. Immediately following an individual oral assessment and again following a group oral assessment, students self-assessed their communication skills using the same rubric the faculty members had used. Students’ self-assessments were then compared with faculty members’ evaluation of students’ communication skills. Results. Four hundred one (97.3%) students consented to participate in this study. Faculty evaluation scores of students for both the individual and group oral assessments were significantly higher than students’ self-assessment scores. Students’ self-assessment scores of their communication skills increased from the individual to the group oral assessment. Conclusion. Students’ self-assessments of communication skills were consistently lower than faculty members’ evaluations. Greater use of oral assessments throughout the pharmacy curriculum may help to improve students’ confidence in and self-assessment of their communication skills.

Abatacept: a novel therapy approved for the treatment of patients with rheumatoid arthritis.

An enhanced understanding of the immunopathology of rheumatoid arthritis (RA) has led to the development of novel therapies that target specific events occurring in the immune cascade that underlies the disease. In December 2005, abatacept became the first therapy to be approved by the US Food and Drug Administration for the treatment of adult patients with moderately to severely active RA who have exhibited an inadequate response to traditional disease-modifying antirheumatic drugs or tumor necrosis factor antagonists. This article summarizes the characteristics and clinical profile of abatacept. Abatacept is a fully human soluble recombinant fusion protein that acts by binding to CD80/CD86 on antigen-presenting cells and inhibiting interaction with CD28 on T cells, thus preventing one of the co-stimulatory signals needed for full T-cell activation. It is indicated for reducing signs and symptoms of the disorder, inducing a major clinical response, slowing the progression of structural damage, and improving physical function in this patient population. Data on abatacept compiled to date demonstrate significant efficacy, combined with a consistent safety profile and tolerability, in a wide range of patients with RA, including those with an inadequate response to methotrexate or to tumor necrosis factor antagonists.

Icatibant for the Treatment of Hereditary Angioedema

OBJECTIVE To review the pharmacology, pharmacokinetics, clinical trials, and safety of icatibant, a recently approved bradykinin B2 receptor antagonist for treatment of acute attacks of hereditary angioedema (HAE). DATA SOURCES Articles indexed in MEDLINE (1948-June 2012), International Pharmaceutical Abstracts(1970-May 2012), and Cumulative Index to Nursing and Allied Health Literature (1981-June 2012) were identified using the search terms icatibant, bradykinin B2 receptor antagonist, and hereditary angioedema. Additional references were identified from the reference lists of the articles identified. STUDY SELECTION AND DATA EXTRACTION English-language articles were reviewed. DATA SYNTHESIS Icatibant was evaluated in 3 Phase 3 clinical trials and found to be a safe and effective option for treatment of acute HAE. Icatibant was compared to placebo in 2 clinical trials (FAST-1 and FAST-3) and to tranexamic acid in the FAST-2 trial. Patients receiving icatibant in FAST-1 did not experience a significant improvement in median time to clinically significant relief of the index symptom (p = 0.14), whereas patients receiving icatibant in FAST-3 experienced a significant improvement in median time to at least 50% reduction in symptom severity (p < 0.001). When icatibant was compared to tranexamic acid in FAST-2, the median time to clinically significant relief of the index symptom was shorter for patients receiving icatibant (p < 0.001). The most common adverse events associated with the administration of icatibant were injection-site reactions, which were mild to moderate and transient. These data suggest that icatibant is a safe and effective treatment for acute attacks of HAE. Although direct comparisons of recently approved alternatives for treatment of acute attacks are lacking, there are administration advantages of icatibant over other agents. Additionally, the cost of icatibant is comparable to that of the C1 esterase inhibitor Berinert and less expensive than ecallantide. CONCLUSIONS Available efficacy data support that icatibant should be considered a safe and effective treatment for acute attacks of HAE. Additionally, limited treatment options for this rare condition, ease of administration, and comparable cost profile support its consideration for formulary inclusion.

Abatacept: a novel treatment for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, autoimmune disease that has traditionally been treated with non-biologic and biologic disease-modifying antirheumatic drugs (DMARDs). Although these agents have become firmly established as effective RA treatments, some patients do not have an adequate response. The recent approval of abatacept, a first-in-class agent that selectively modulates the activation of T cells, offers an alternative therapeutic option. As reflected in pharmacokinetic analyses, abatacept 10 mg/kg has been shown to be effective in treating patients with established RA. Demonstrating safety, efficacy and quality of life improvements in a wide range of RA patients, including those with inadequate response to methotrexate or tumor necrosis factor antagonists, abatacept is seen as a valuable addition to the RA treatment armamentarium.

Student Pharmacists’ Clinical Interventions in Advanced Pharmacy Practice Experiences at a Community Nonteaching Hospital

Objective. To assess student pharmacists’ clinical interventions in advanced pharmacy practice experiences (APPEs) at a community nonteaching hospital and evaluate completed interventions based on the type of documentation method used. Methods. Clinical interventions of 120 fourth-year (P4) student pharmacists in advanced institutional, medication safety, or internal medicine APPEs were collected over a 3½-year period. Clinical interventions were analyzed for cost savings, intervention type, and acceptance rates. A secondary analysis of paper-based vs electronic-based documentation of completed interventions was performed. Results. There were 2,170 clinical interventions attempted with an acceptance rate of 97%. The estimated cost savings was

Spinosad for Treatment of Head Lice Infestation

280,297. A comparable number of interventions and cost savings per student was observed between paper-based and electronic-based documentation methods. Conclusion. Student pharmacists at a community nonteaching hospital have many opportunities for participation in patient-centered activities, and for interaction and collaboration with other healthcare professionals. They can significantly benefit patient care through clinical interventions, while also contributing to cost savings for the institution.

A review of the advances in chronic obstructive pulmonary disease treatment.

Objective: To review the pharmacology, pharmacokinetics, clinical trials, and safety profile of spinosad 0.9% topical lotion, a recently approved pediculicide for treatment of head lice infestation. Data Sources: English-language articles indexed in MEDLINE (1948-May 2011), Toxline, Google Scholar, International Pharmaceutical Abstracts (1970-May 2011), and Cumulative Index to Nursing and Allied Health Literature (1981-May 2011) were identified, using the search terms spinosad, head lice, and pediculosis capitis. Study Selection and Data Extraction: Available English-language articles were reviewed. Data Synthesis: In the studies that were reviewed, the percentage of patients who were lice free 14 days after the last treatment was significantly higher in the spinosad groups compared to the permethrin groups (84.6% vs 44.9% and 86.7% vs 42.9%, respectively; p < 0.001 for both studies). Additionally, the proportion of all primary and nonprimary participants determined to be lice free following only 1 treatment with the study medication was higher among patients in the spinosad groups compared with those in the permethrin groups. Application-site erythema was observed in patients in both treatment groups; however, it was more common in patients in the permethrin groups compared with those receiving spinosad (6.8% vs 3.1%, respectively; p = 0.007). No serious adverse effects were reported by patients receiving spinosad. Adherence was higher in the spinosad groups compared with the permethrin groups, although adherence overall was high in both studies. These data suggest that spinosad is a safe and effective treatment for the eradication of head lice, and the ease of administration and improved adherence with spinosad could offer an advantage over currently available treatment options. Conclusions: Because of its established efficacy, favorable safety profile, and ease of application, spinosad can be considered a convenient and effective treatment for head lice in patients aged 4 years and older.

Ciprofloxacin-Induced Hepatotoxicity Resolved With Levofloxacin: A Case Report and a Review of the Literature

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality across the globe and within the United States. Although several medication classes are used for COPD treatment, none of these medications have been shown to significantly improve long-term lung function or mitigate overall disease progression. This review describes the pharmacologic treatment options for COPD and highlights recent studies evaluating the impact of bronchodilators and combination therapy on lung function, mortality, quality of life, and exacerbations. Additionally, indacaterol and roflumilast, 2 new COPD treatment agents approved by the Food and Drug Administration in 2011, are discussed. Pharmacists play an important role in managing and educating patients with COPD and should utilize new evidence to make recommendations.

Critical appraisal of efficacy and safety of abatacept in the treatment of refractory rheumatoid arthritis

Objective To report a case of elevated hepatic transaminases in a patient receiving ciprofloxacin that resolved upon discontinuation and initiation of levofloxacin. Summary A 45-year-old white woman was initiated on ciprofloxacin and gentamicin after a blood culture revealed gram-negative rods. On day 2 of antibiotic therapy, the patients aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased to 2,352 units/L and 783 units/L, respectively, and remained elevated for the following 4 days. Baseline AST and ALT were within normal limits. On day 5 of therapy, ciprofloxacin was discontinued and levofloxacin was initiated. On the following day, the hepatic transaminases decreased (AST, 192 units/L; ALT, 582 units/L) and continued to normalize prior to hospital discharge. On a subsequent admission later in the month, levofloxacin was again administered for treatment of a gram-positive bacteremia, with no subsequent elevation of hepatic transaminases. Discussion An objective causality assessment revealed that the adverse drug reaction (ADR) was probable. Although reports of this ADR have been noted, there is no previously documented occurrence of resolution of elevated hepatic transaminases on therapeutic modification to another fluoroquinolone. Conclusion Ciprofloxacin may significantly elevate hepatic transaminases. The clinician should be aware of the unique ADR profiles of the different fluoroquinolones because hepatotoxicity may not be a class effect.