Ixekizumab: A Review of Its Use for the Management of Moderate to Severe Plaque Psoriasis.

OBJECTIVE: To review the efficacy, safety, and place in therapy of ixekizumab for the treatment of moderate to severe plaque psoriasis. DATA SOURCES: PubMed (1966 to July 2018) and clinicaltrials.gov were searched using the terms ixekizumab, LY2439821, interleukin-17, and psoriasis. STUDY SELECTION AND DATA EXTRACTION: Human studies published in peer-reviewed medical journals in English were used. DATA SYNTHESIS: The efficacy and safety of ixekizumab has been primarily reported by 4 phase III trials (UNCOVER-1, UNCOVER-2, UNCOVER-3, and UNCOVER-J) and multiple post hoc analyses. The average proportions of patients achieving a 75%, 90%, and 100% reduction in their Psoriasis Area and Severity Index (PASI) were 89%, 70%, and 38%, respectively, after 12 weeks of therapy. PASI75 was maintained for up to 3 years in 80.5% of participants. Ixekizumab was statistically significantly more effective than ustekinumab, with 76.5%, compared with 59%, of patients achieving PASI90 in 52 weeks. The most common adverse events include nasopharyngitis (14.1%), upper respiratory tract infections (7.9%), and injection-site reactions (6.8%), which are similar to that for other biological agents. The risk of inflammatory bowel disease may be increased with ixekizumab. Relevance to Patient Care and Clinical Practice: This review summarizes and evaluates clinical data regarding the efficacy and safety of ixekizumab and discusses relevant differences compared with other biological agents used for the management of chronic plaque psoriasis. CONCLUSIONS: Ixekizumab is a highly efficacious and well-tolerated treatment option for patients with moderate to severe plaque psoriasis.

Memantine for the prevention of primary headache disorders.

OBJECTIVE: To describe the current data evaluating the efficacy and safety of memantine for the prevention of primary headache disorders. DATA SOURCES: A literature search using MEDLINE (1966-July 2014) and EMBASE (1973-July 2014) was conducted using the search terms memantine, headache, migraine, glutamate, and NMDA. References of identified articles were reviewed for additional, relevant citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles dealing with the use of memantine for prevention of primary headache disorders were included. DATA SYNTHESIS: Data from several retrospective reports and 2 prospective clinical trials suggest that memantine may be a useful treatment option for the prevention of primary headache disorders. The majority of available literature focuses specifically on chronic migraine prevention in refractory patients who had failed multiple previous prophylactic therapies. In these patients, 10 to 20 mg of memantine daily reduced the frequency and intensity of migraine headaches and was generally well tolerated, with few adverse events. Data regarding the efficacy of memantine for other primary headache disorders such as chronic tension type and cluster headaches are limited. CONCLUSION: Although further studies evaluating the efficacy of memantine for prevention of primary headache disorders are warranted, memantine may be a reasonable option, used either as monotherapy or adjunctive therapy, in the refractory chronic migraine prophylaxis setting.

Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease.

OBJECTIVE: To describe the current data evaluating the efficacy and safety of ipratropium used in combination with tiotropium in patients with chronic obstructive pulmonary disease. DATA SOURCES: A literature search using MEDLINE (1966-August 2012) and EMBASE (1973-August 2012) was conducted using the search terms ipratropium, tiotropium, combination drug therapy, and chronic obstructive pulmonary disease. References of identified articles were reviewed for additional relevant citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles regarding the concomitant use of ipratropium and tiotropium were reviewed. DATA SYNTHESIS: Two prospective randomized controlled trials have demonstrated increases in bronchodilation with ipratropium when added to maintenance tiotropium therapy, suggesting potential benefits during short-term, combined use. One study reported significantly higher peak forced expiratory volume in 1 second (FEV(1)) responses with both ipratropium (230 mL) and fenoterol (315 mL) compared to placebo (178 mL) when added to maintenance tiotropium. The peak response with fenoterol was significantly higher than with ipratropium (FEV(1) difference = 84 mL). Another study reported a mean difference in FEV(1) of 81 mL (95% CI 27 to 136) with albuterol versus placebo and a mean difference in FEV(1) of 68 mL (95% CI 3 to 132) with ipratropium versus placebo. The difference between albuterol and ipratropium when added to maintenance tiotropium was not significant. One large observational study reported a significantly higher risk of acute urinary retention in individuals receiving combination therapy with a short- and long-acting anticholinergic agent compared to those receiving monotherapy (OR 1.84; 95% CI 1.25 to 2.71). Individuals at highest risk were men and those with evidence of benign prostatic hypertrophy. CONCLUSIONS: While ipratropium may provide spirometric improvements in lung function for patients receiving tiotropium maintenance therapy, the clinical significance of these improvements has not been documented and the risk of anticholinergic adverse effects is increased with combination therapy. Further studies evaluating the safety and efficacy of concomitant ipratropium and tiotropium are warranted before combination use can be recommended for select patients.

An evidence-based systematic review of saffron (Crocus sativus) by the Natural Standard Research Collaboration.

An evidence-based systematic review including written and statistical analysis of scientific literature, expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

Prazosin treatment of nightmares related to posttraumatic stress disorder.

OBJECTIVE: To describe current data evaluating the use of prazosin in adults with posttraumatic stress disorder (PTSD) who are experiencing nightmares. DATA SOURCES: A literature search using MEDLINE (1966-March 2007) and the Published International Literature on Traumatic Stress database (1982-March 2007) was conducted using the search terms alpha-antagonist, alpha-blocker, prazosin, and posttraumatic stress disorder. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: All English-language articles regarding the use of prazosin in adults with nightmares related to PTSD were reviewed. DATA SYNTHESIS: PTSD is a psychiatric disorder that develops in some people after exposure to trauma. Sleep disturbances occur in up to 70% of patients with PTSD. Several neurotransmitters have been implicated in the pathophysiology of sleep disturbances in PTSD. Adrenergic agents that inhibit norepinephrine, such as prazosin, may decrease the arousal produced by norepinephrine in response to a stressor. Four open-label studies, 1 retrospective chart review, and 2 placebo-controlled trials reporting the use of prazosin for nightmares related to PTSD were reviewed. All studies included a small number of patients (4-59) and evaluated prazosin dosages ranging from 1 to 20 mg/day. Despite various limitations, all of the studies showed significant improvements in the sleep-related symptoms of PTSD following the addition of prazosin therapy, based on the Clinician Administered PTSD Scale recurrent distressing dreams item and the Clinical Global Impression of Change scale. CONCLUSIONS: Prazosin appears to be a promising and fairly well tolerated agent for the management of PTSD-related nightmares and sleep disturbances. Further well designed trials are warranted to establish its place in therapy.

Efalizumab for the treatment of moderate to severe plaque psoriasis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of efalizumab for the treatment of moderate to severe plaque psoriasis. DATA SOURCES: A MEDLINE search (1966-May 2005) using the key words hu1124, anti-CD11a, efalizumab, Raptiva, Xanelim, and psoriasis was conducted. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the pharmacology, efficacy, and safety of efalizumab for treatment of moderate to severe plaque psoriasis in adults were included in our review. DATA SYNTHESIS: Efalizumab's ability to inhibit the binding of CD11a, a subunit of leukocyte function-associated antigen type 1, to intracellular adhesion molecule 1 results in decreased T-cell activation and migration, 2 key steps in the immunopathogenesis of psoriasis. Results of clinical trials have demonstrated that efalizumab administered subcutaneously is a safe and effective treatment for moderate to severe plaque psoriasis. Efalizumab was well tolerated in trials, with the majority of adverse events arising with the first dose and decreasing with subsequent doses. The high cost of this agent and lack of head-to-head trials with other drugs will likely restrict its use to patients who have failed prior systemic therapy or phototherapy. CONCLUSIONS: Efalizumab is a safe and effective therapy for treatment of moderate to severe plaque psoriasis in patients who have failed prior systemic therapy or phototherapy.