Nov 202013
 
Related Articles

Eculizumab: A Review of Its Use in Atypical Haemolytic Uraemic Syndrome.

Drugs. 2013 Nov 19;

Authors: Keating GM

Abstract
The recombinant humanized monoclonal antibody eculizumab (Soliris(®)) is a complement inhibitor that is indicated for use in the treatment of atypical haemolytic uraemic syndrome (aHUS). This article reviews the clinical efficacy and tolerability of eculizumab in the treatment of patients with aHUS, as well as summarizing its pharmacological properties. Intravenous eculizumab inhibited complement-mediated thrombotic microangiopathy in patients aged ≥12 years with aHUS, according to the results of two noncomparative, multinational, 26-week, phase II trials. At 26 weeks, the platelet count was significantly increased in patients with progressing thrombotic microangiopathy despite plasma exchange/infusion, and thrombotic microangiopathic event-free status was achieved in 80 % of patients with a long disease duration and chronic kidney disease who received long-term plasma exchange/infusion. Renal function and health-related quality of life also improved with eculizumab therapy in both studies. Outcomes were maintained or further improved throughout 2 years of follow-up. Eculizumab was also effective in adult and paediatric patients with aHUS, according to the results of additional prospective or retrospective trials. Intravenous eculizumab was generally well tolerated in patients with aHUS. Eculizumab is associated with an increased susceptibility to meningococcal infection, so patients should be immunized with meningococcal vaccine. In conclusion, eculizumab is a valuable new agent for use in the treatment of aHUS.

PMID: 24249647 [PubMed - as supplied by publisher]

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Nov 202013
 
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Modified-Release Prednisone: in Patients with Rheumatoid Arthritis.

Drugs. 2013 Nov 19;

Authors: Henness S, Yang LP

Abstract
Prednisone is a well-established treatment option in rheumatoid arthritis. Low-dose glucocorticoid therapy alleviates disease signs and symptoms, is better tolerated than high-dose therapy, and its addition to disease-modifying anti-rheumatic drugs (DMARDs) inhibits radiographic disease progression. A low-dose, modified-release (MR) formulation of prednisone, administered in the evening, was developed to counter the circadian rise in pro-inflammatory cytokine levels that contributes to disease activity. In a 12-week, randomized trial (CAPRA-2) in adult patients with rheumatoid arthritis who were receiving stable DMARD therapy, the addition of MR prednisone reduced disease signs and symptoms by ≥20 % according to the American College of Rheumatology criteria (in 48 % of patients vs. 29 % with placebo; p < 0.002 [primary endpoint]). In another 12-week trial (CAPRA-1), addition of evening MR prednisone to stable DMARD therapy reduced the mean duration of morning stiffness to a greater extent than addition of morning immediate-release (IR) prednisone (22.7 vs. 0.4 %; p = 0.045 [primary endpoint]). The improvement in morning stiffness with MR prednisone was maintained for 9-12 months during the open-label extension of CAPRA-1. These findings were supported by data from observational studies in various adult populations with rheumatoid arthritis. Treatment with evening MR prednisone for up to 12 months was generally well tolerated, with an overall similar tolerability profile compared with evening placebo or morning IR prednisone, and no new safety concerns. MR prednisone was estimated to be cost effective relative to IR prednisone in patients with rheumatoid arthritis in a UK pharmacoeconomic model.

PMID: 24249648 [PubMed - as supplied by publisher]

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Nov 132013
 
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Riociguat: First Global Approval.

Drugs. 2013 Nov 12;

Authors: Conole D, Scott LJ

Abstract
Riociguat (Adempas(®)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). The drug directly stimulates sGC in a nitric oxide independent manner, thereby increasing the sensitivity of sGC to nitric oxide, leading to increased cyclic guanosine monophosphate generation (a key signalling molecule involved in regulating vascular tone, proliferation, fibrosis and inflammation). Riociguat is the world's first approved pharmacotherapy for CTEPH, with its first global approval in this indication occurring in Canada. It has subsequently been approved in the USA for the treatment of patients with CTEPH and also received its first global approval in patients with PAH in the USA. It is undergoing regulatory review for these indications in Europe and for use in patients with CTEPH in Japan. This article summarizes the milestones in the development of riociguat, leading to its first global approvals in patients with CTEPH and PAH.

PMID: 24218053 [PubMed - as supplied by publisher]

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Nov 122013
 

Should Mild COPD Be Treated? Evidence for Early Pharmacological Intervention.

Drugs. 2013 Nov 9;

Authors: Elbehairy AF, Webb KA, Alberto Neder J, O'Donnell DE

Abstract
Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways that is both preventable and treatable. It is well established that those with mild-to-moderate disease severity represent the majority of patients with COPD, yet this subpopulation is relatively under-studied. Because of an insidious pre-clinical phase, COPD is both under-diagnosed and under-treated. Recent studies have confirmed that even patients with mild, grade 1 COPD [i.e. those with a reduced forced expiratory volume in one second (FEV1)/forced vital capacity ratio but normal FEV1], have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with non-smoking healthy controls. Beyond the imperative of smoking cessation-the pivotal intervention in all COPD stages-the role of pharmacotherapy for prevention of disease progression has yet to be established. The main objective of this review is to provide a concise overview of the heterogeneous pathophysiology of COPD with only mild airway obstruction on spirometry and obstacles for early diagnosis. We emphasize that the absence of sufficiently powered trials involving a large number of patients precludes definitive recommendations in support of (or against) long-term pharmacological treatment in mild COPD. Despite these limitations, we present a rationale for earlier pharmacological intervention derived from recent physiological studies performed in symptomatic patients with mild COPD.

PMID: 24214364 [PubMed - as supplied by publisher]

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Nov 072013
 
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Prucalopride: A Review of Its Use in the Management of Chronic Constipation.

Drugs. 2013 Nov 6;

Authors: Keating GM

Abstract
The highly selective serotonin 5-HT4 receptor agonist prucalopride (Resolor(®), Resotran(®), Resotrans(®)) is indicated for the treatment of chronic constipation. In four randomized, double-blind, multicentre, 12-week trials in patients (predominantly women) with chronic constipation, oral prucalopride 2 mg once daily improved bowel function to a significantly greater extent than placebo, with a significantly greater proportion of prucalopride than placebo recipients achieving an average of ≥3 spontaneous, complete bowel movements per week (primary endpoint). Significantly greater improvements in health-related quality of life, patient satisfaction with treatment and bowel habit, and a range of constipation-related symptoms were also seen with prucalopride than with placebo. Satisfaction with treatment and bowel habit was maintained with prucalopride in the longer term. Prucalopride was generally well tolerated in patients with chronic constipation, with the most commonly reported adverse events (headache, nausea, abdominal pain, diarrhoea) primarily occurring on the first day of treatment. During the clinical trials, no cardiovascular safety issues have arisen in patients with chronic constipation receiving prucalopride. In conclusion, prucalopride is an important option for use in patients with chronic constipation who have not experienced adequate relief with laxatives.

PMID: 24194435 [PubMed - as supplied by publisher]

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Nov 072013
 
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Tobramycin Inhalation Powder: A Review of Its Use in the Treatment of Chronic Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis.

Drugs. 2013 Nov 6;

Authors: McKeage K

Abstract
Inhaled tobramycin, an aminoglycoside antibacterial, has been in widespread use in the form of a nebulized solution against Pseudomonas aeruginosa for many years. More recently, tobramycin inhalation powder (TIP; TOBI(®) Podhaler(™)) was formulated using PulmoSphere(™) technology for administration as a dry powder via the T-326 Inhaler. This technology enables the administration of an intrapulmonary drug dose that is similar to that achieved with nebulized tobramycin inhalation solution (TIS), but reduces the administration time for TIP to one-third of that for TIS. TIP is approved in several countries, including the EU and US, for use in cystic fibrosis (CF) patients aged ≥6 years with P. aeruginosa infection. In well designed clinical trials in CF patients, the antipseudomonal efficacy of intermittent twice-daily TIP 112 mg was greater than that of placebo in one trial (a second trial was unable to recruit sufficient patient numbers for meaningful analyses), and non-inferior to that of intermittent twice-daily nebulized TIS 300 mg/5 mL with regard to lung function and sputum density of P. aeruginosa. In addition, patients using TIP were more satisfied with their treatment than those using nebulized TIS, largely as a result of improved overall convenience. TIP is generally well tolerated, with a similar safety profile to that of TIS, except for a higher incidence of cough. In conclusion, TIP administered via the T-326 Inhaler is an effective antipseudomonal agent with non-inferior efficacy and generally similar tolerability to that of nebulized TIS in CF patients with chronic P. aeruginosa infection. Compared with nebulized TIS, TIP has a faster delivery and is more portable and convenient.

PMID: 24194436 [PubMed - as supplied by publisher]

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