Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

[Use of oral drugs and short bowel syndrome: an analysis of practices]. / Utilisation des médicaments par voie orale et syndrome de grêle court : analyse des pratiques.

OBJECTIVE: To describe drug prescription patterns in patients with short bowel syndrome (SBS). METHODS: The drug prescriptions of patients suffering from SBS type 1 to 3 were compared. RESULTS: Seventy-nine percent of the drugs were prescribed by oral route, and this proportion was significantly higher in patients with type 3 compared to tose with type 1. Twenty-nine percent of prescriptions were dietary supplement-drugs, 14.3% were gastrointestinal drugs and 11.4% were cardiovascular drugs. Oral prescription medications for SBS concerned many drug categories. The number of gastrointestinal or dietary supplement drugs was comparable between the 3 types. Drug doses were not increased compared with the recommendations, except for gastrointestinal drugs. CONCLUSION: The oral administration is common and at usual dosage in patients with SBS despite a lack of studies on absorption that may help to individualize drug prescription.

Efficacy and safety of three ophthalmic inserts for topical anaesthesia of the cornea. An exploratory comparative dose-ranging, double-blind, randomized trial in healthy volunteers.

BACKGROUND: Cataract surgery requires prolonged anaesthesia, concomitant with permanent hydration and lubrication of the cornea, in order to provide a clear view of the operation area. AIMS: The primary objective of the study was to assess several formulae of a soluble ophthalmic insert: TOPICSERT [bupivacaine (Bupi) + hyaluronic acid (HA) or sodium hyaluronate] in terms of complete and long-lasting anaesthesia of the cornea. The hydration properties of HA were not assessed in this study. METHODS: In a prospective double-blind, cross-over, randomized study, with latin-square allocation of treatments, 16 healthy volunteers received a single dose of each formula (A, 1 mg Bupi and 0.1 mg HA; B, 0.5 mg Bupi and 0.1 mg HA; C, 1 mg Bupi and 0 mg HA, and D acting as a placebo) via the ocular route with 1 week of wash-out between each period. Corneal anaesthesia was measured using a Cochet-Bonnet esthesiometer. RESULTS: There was a statistically significant difference between treatments with regard to the main criterion (complete anaesthesia lasting at least 20 min) when general association statistics were used (Mantel-Haenzel test, P < 0.0001): 68.75% (n = 11) of subjects receiving treatment A, 37.5% (n = 6) receiving treatment B, and 87.5% (n = 14) on treatment C reached complete and satisfactory anaesthesia, while this was not achieved in any of the subjects receiving placebo. Ninety-five percent confidence intervals of the difference between treatments were as follows: treatment A vs. B (-0.03, 0.66), treatment A vs. C (-0.47, 0.10), treatment B vs. C (-0.84, - 0.16). Only the difference between B and C was statistically significant (adjusted probability by the method of Bonferroni, P < 0.001). When complete anaesthesia was reached, mean (+/-SD) duration of anaesthesia was as follows: 20.7 (+/-6.5), 15.3 (+/-11.4) and 24.7 (+/-7.6) min for treatments A, B, C, respectively. CONCLUSIONS: Bupivacaine 1 mg seems to be the efficient and safe dose. The value of hyaluronic acid as a corneal hydration agent and used in association with bupivacaine will be the subject of further studies.

Effects of the addition of high-dose vitamin C to polyethylene glycol solution for colonic cleansing: A pilot study in healthy volunteers.

BACKGROUND: Polyethylene glycol (PEG) solutions, with or without osmotic agents, are used to empty the large intestine before procedures such as colonoscopy or colonic surgery. Data concerning the effectiveness of vitamin C as an ingredient in colonic preparations are scant. OBJECTIVE: The aim of this article was to assess the effectiveness, acceptability, and tolerability of 6 preparations of a standard PEG electrolyte solution containing different doses of PEG, vitamin C (as an osmotic agent), and sodium sulfate in colonic cleansing. METHODS: This double-blind, randomized, 2-period crossover study was conducted at the Lariboisière Hospital, Paris, France. Healthy adult volunteers were randomly assigned to receive 2 of 6 colonic cleansing preparations, each containing different doses of PEG (100 or 125 g/L), vitamin C (0, 5, or 10 g/L, in the form of sodium ascorbate, ascorbic acid, or a mixture of both), and sodium sulfate (5 or 7.5 g/L), diluted in water to a volume of 2 L. Study drug administration was separated by a washout period of 7 to 15 days, after which the volunteers received an alternate preparation. Stools were collected for 10 hours after the start of solution ingestion. The primary efficacy end point was stool volume. Secondary end points included acceptability of taste, assessed using a 100-mm visual analog scale (VAS) (0 = excellent to 100 = execrable), taste criteria (saltiness, acidity, and sweetness, assessed on a 4-point Likert-type scale [0 = very pleasant to 3 = intolerable]) and tolerability (clinical effects [changes in body weight, blood pressure, heart rate, and nausea and vomiting] and biologic effects [changes in serum electrolytes, creatinine, hematocrit, and ascorbic acid]). RESULTS: Thirty volunteers (15 men, 15 women; mean [SD] age, 29.8 [8.2] years [range, 20-45 years]) were enrolled and completed the study. Mean (SD) stool volume obtained with preparations containing 10 g/L of vitamin C did not differ significantly from the volume obtained without vitamin C (2.54 [0.54] L vs 1.93 [0.62] L; 95% CI, -0.13 to 1.47). Mean (SD) VAS scores for acceptability of taste ranged from 54.4 (25.0) (preparation E) to 74.4 (20.1) (preparation C) (P = 0.03 preparation E vs all other preparations). The only significant difference in taste criteria was in acidity, with preparation A being the least acidic according to patients' ratings on the VAS (1.4 [0.7] vs 1.8 [0.4] [mean of the other 5 preparations combined]; P = 0.04 preparation A vs all other preparations). Mild dehydration occurred in 6 subjects (1 for each preparation). No clinical or biological adverse effects were found. CONCLUSIONS: In this study of 6 colonic cleansing preparations in healthy volunteers, the use of high-dose vitamin C as an osmotic agent in addition to PEG did not significantly increase stool output. All 6 preparations were well tolerated.

Interaction between cyclooxygenase and the renin-angiotensin-aldosterone system: rationale and clinical relevance.

Increased understanding of pathophysiological mechanisms of cardiovascular diseases has shown that the renin-angiotensin-aldosterone system (RAAS) is activated in this setting and suggests a central role for the angiotensin-converting enzyme (ACE). ACE transforms angiotensin I (Ang I) to angiotensin II (Ang II), and also promotes the degradation of bradykinin into inactive metabolites. These bradykinins stimulate nitric oxide synthesis and vasodilatator prostaglandin synthesis via a cyclooxygenase (COX) pathway. COX inhibitors may therefore be deleterious in cardiovascular disease and/or counteract part of ACE inhibitor (ACE-I) efficacy. This has been clearly demonstrated with non-steroidal anti-inflammatory drugs (NSAIDs), including high-dose aspirin, in hypertension, coronary artery disease and chronic heart failure (CHF); most guidelines recommend avoiding their use in such patients. Theoretically, this effect is dose-mediated and the existence of an identical deleterious effect with low-dose aspirin has been an area of intense debate. In this article, we review studies, most of them conducted in CHF, that pointed out such a possible deleterious effect and a counteraction of ACE-Is with low-dose aspirin, using various criteria of assessment. However, there are no prospective long-term studies that have validated such an effect, and the role of other anti-aggregating agents has not been evaluated. Until such studies are published, the use of low-dose aspirin (100 mg/day) in such patients can be recommended.