Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control.

INTRODUCTION: Severe persistent asthma represents a major and costly public health issue. There is evidence that long-term treatment with omalizumab might have disease-modifying activity but data on the consequences of discontinuing treatment after a positive response are limited. The purpose of this study was to investigate-in real-life prescribing conditions-what happens when omalizumab is discontinued in patients with severe, persistent allergic asthma who have responded well to omalizumab treatment. METHODS: An observational, descriptive, cross-sectional, retrospective study to establish the time to loss of asthma control after the discontinuation of courses of omalizumab treatment of varying duration. RESULTS: 24 lung specialists reviewed data from 61 responder patients who had discontinued omalizumab after a mean duration of 22.7 ± 13.1 [range: 2.5; 59.5] months of treatment. Loss of asthma control was documented in 34 patients (55.7%) with a median interval between discontinuation and loss of control of 13.0 months (mean 20.4 ± 2.6 [95% CI: 8.3-28.1]). No correlation was detected between time to loss of control and duration of treatment, although control tended to be sustained for longer in patients whose response had been classified as "excellent" as opposed to "good" (median: 17.0 vs. 12.8 months; NS). DISCUSSION: The discontinuation of omalizumab was not associated with any rebound effect or exacerbation of the disease, and control was sustained throughout the follow-up period of at least 6 months in nearly half of all patients, including all of those who had been treated for 3.5 years or more. After the reintroduction of omalizumab, 4 out of 20 patients did not respond again.

Diagnosis of Alzheimer's disease patients with rapid cognitive decline in clinical practice: interest of the Deco questionnaire.

BACKGROUND: Patients with Alzheimer's disease (AD) who deteriorate rapidly are likely to have a poorer prognosis. There is a clear need for a clinical assessment tool to detect such a decline in newly diagnosed patients. OBJECTIVE: To identify the predictive factors of rapid cognitive decline (RCD) in a cohort of patients with mild to moderate AD ; and to validate a self-questionnaire for caregivers as a diagnostic tool for rapid decline. DESIGN AND ANALYSIS: An open-label, observational, 12-month, multicenter, French study. Physicians were asked to record data of three eligible rivastigmine naïve (or on rivastigmine for < 1 year) AD patients. Risk factors of RCD and the detection power of the Détérioration Cognitive Observée scale (Deco), a 19 item self-questionnaire for caregivers, were assessed at endpoint using regression analyses. RESULTS: Out of the 361 patients enrolled in the study, 91 (25.2%) were excluded due to loss of follow-up. Among subjects using cholinesterase inhibitors or memantine, 161 (59.6%) experienced a stabilization (29.2%) or an improvement (30.4%) in global functioning as measured by the CGI-C. Sixty of the remaining 204 patients retained for analysis (29.6%, CI 95% [23.4; 35.8]) lost three or more points on the MMSE score between the inclusion and one of the follow-up visit. In the multivariate logistic regression analysis, institutionalization, higher level of education and the loss of 3 points or more on the MMSE were found to be significant predictors of a rapid cognitive loss in this population. The threshold which maximizes the predictive values of the Deco score as a diagnostic tool of rapid cognitive decline was significantly different according to the age of the patient (below or over 75 years old). A score below 16 for patients < 75 years old and below 14 for patients ≥ 75 years old consistently predicted a RCD within the next year. CONCLUSION: The Deco test appears to be a simple tool to alert the physician to the possibility of an aggressive course of the disease which warrants particular management.

Levodopa/DDCI and entacapone is the preferred treatment for Parkinson's disease patients with motor fluctuations in routine practice: a retrospective, observational analysis of a large French cohort.

Levodopa is the gold standard drug for the symptomatic control of Parkinson's disease (PD). However, long-term treatment with conventional formulations [levodopa and a dopa decarboxylase inhibitor (DDCI)], is associated with re-emergence of symptoms because of wearing-off and dyskinesia. Treatment with levodopa/DDCI and entacapone extends the half-life of levodopa, avoiding deep troughs in levodopa plasma levels and providing more continuous delivery of levodopa to the brain. In this open-label, retrospective, observational study we investigated the effects of levodopa/DDCI and entacapone therapy in 800 PD patients with motor fluctuations. Levodopa/DDCI and entacapone treatment was assessed as good/very good in improving motor fluctuations (64%) and activities of daily living (ADL; 62%). The therapeutic utility was considered to be good/very good in 70% of cases. Moreover, there was a reduction in levodopa dose in 20% of patients. Neurologists preferred levodopa/DDCI and entacapone compared with increasing levodopa dosage, dose-fractionation or addition of a dopamine agonist (63%, 29% and 23% of patients respectively). Reasons included achieving more continuous dopaminergic stimulation (40%), reducing motor fluctuations (54%) and improving ADL (41%). This analysis reveals the preference of neurologists for levodopa/DDCI and entacapone over conventional levodopa-modification strategies for the effective treatment of PD motor fluctuations in clinical practice.

[Precoce survey: a new self-assessment patient card for early detection and management of Parkinson disease fluctuations]. / Etude Précoce: évaluation d'un autoquestionnaire de dépistage et prise en charge précoces des fluctuations dans la maladie de Parkinson.

It has been known for more than 30 years that the efficiency of the dopaminergic treatments can wear off. Currently, motor fluctuations and especially non-motor fluctuations (dysautonomic, cognitive/psychiatric or sensory/pain) remain often underdiagnosed in the first years of treatment. The patient self-questionnaire used in this study has been developed and validated in the United States. Its French version has been tested in daily practice in a study with 938 Parkinson's patients followed-up by movement disorders specialists. Use of this self-assessment patient card has resulted in the detection of fluctuations in 49% of patients, considered nonfluctuating by neurologists after a clinical assessment. The impact of these fluctuations unknown at first is significant, since these motor and/or non motor symptoms are considered troublesome or perturbing for daily life activities by 70% of fluctuating patients. The investigators have recognized the usefulness of this self-assessment in order to detect fluctuations in 81% of fluctuating patients, which lead them to modify the treatment in 76% of them.

Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment.

We investigated the efficacy and safety of rivastigmine alone and combined with memantine in Alzheimer's disease patients previously failing on donepezil or galantamine. This was a prospective, open-label, multicentre study. After stopping donepezil or galantamine, patients received rivastigmine 3-12 mg/day for 16 weeks. Non-responders to rivastigmine monotherapy at week 16 received memantine 5-20 mg/day plus rivastigmine for 12 weeks. The primary efficacy parameter was response (Mini-Mental State Examination equal or better than at week 16) to dual therapy at week 28. Secondary criteria were changes on cognitive and behavioural scales. Two hundred and two patients were included. Ninety-three (46.3%) patients responded to rivastigmine monotherapy. Of 86 patients receiving additional memantine for another 12 weeks, 67 (77.9%) responded. Combination therapy caused no apparent safety concerns. When patients fail on donepezil or galantamine, switching to rivastigmine may improve cognition and behaviour. Should they continue to deteriorate, the addition of memantine may be beneficial.

Octreotide (long-acting release formulation) treatment in patients with graves' orbitopathy: clinical results of a four-month, randomized, placebo-controlled, double-blind study.

There are few effective, safe modalities for the management of Graves' ophthalmopathy (GO), a cell-mediated immune comorbidity of thyroid disease. Somatostatin analogs inhibit lymphocyte proliferation and activation, and accumulate in the orbital tissue of patients with GO. A double-blind, placebo-controlled study of a long-acting somatostatin analog [16 wk of long-acting release formulation of octreotide (octreotide-LAR)] was conducted in 51 patients with mild active GO with the aim of preventing deterioration and precluding the need for more aggressive therapeutic modalities, such as glucocorticoids or radiotherapy. No treatment effect was observed for the primary end point (a composite parameter defining the outcome as either success or failure on the basis of changes in class/grade of the severity index and Clinical Activity Scale of GO). The Clinical Activity Scale score was reduced for patients treated with octreotide-LAR, but without any significant difference with respect to patients receiving placebo. However, octreotide-LAR significantly reduced proptosis (as measured by exophthalmometry). This was associated with nonsignificant differences in favor of octreotide-LAR in a series of proptosis-related parameters: class III grade, opening of the upper eyelid, the difference in ocular pressure between primary position and upgaze, and extraocular muscle involvement. By magnetic resonance imaging evaluation the extraocular muscle volumes appeared reduced, but nonsignificantly. No significant correlation between the initial uptake of the somatostatin analog indium-labeled and the response to treatment was observed. One patient in the octreotide-LAR group developed gallstones. In this study, octreotide-LAR did not seem suitable to mitigate activity in mild GO. Surprisingly, it significantly reduced proptosis, one of the most debilitating symptoms of GO. Additional studies are warranted to define the benefit to risk ratio of the somatostatin analogs in this indication.

Clozapine in drug induced psychosis in Parkinson's disease: a randomised, placebo controlled study with open follow up.

OBJECTIVE: To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson's disease (PD). METHODS: A four week, randomised, double blind, parallel comparison of clozapine and placebo, followed by a 12 week clozapine open period, plus a one month period after drug discontinuation, in 60 patients with PD. The primary efficacy outcome was the "clinical global impression scale" (CGI); the positive subscore of the "positive and negative syndrome scale" (PANSS) was used as the secondary efficacy parameter and the "unified Parkinson's disease rating scale" (UPDRS) and the "mini mental test examination" (MMSE) as safety outcomes. RESULTS: The mean (SD) dosage of clozapine was 35.8 (12.5-50) mg at the end of the double blind period. The mean (SD) scores on the CGI improved by 1.8 (1.5) for the clozapine group compared with 0.6 (1.1) for the placebo group (p = 0.001). The mean (SD) positive subscore of PANSS improved by 5.6 (3.9) for the clozapine group (0.8 (2.8) for the placebo group; p < 0.0001). At the end of the open period, 25 patients had completely recovered from delusions and hallucinations, and 19 experienced a relapse within one month after the clozapine washout period. The UPDRS motor and MMSE mean scores did not change significantly in either group. Somnolence was more frequent with clozapine than with placebo. CONCLUSIONS: Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.

Efficacy and tolerability of entacapone in patients with Parkinson's disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations. A randomized, double-blind, multicentre study.

The efficacy and tolerability of entacapone was investigated in a randomized, double-blind, placebo-controlled, 3-month study of 162 patients with Parkinson's disease (PD) treated with levodopa and a dopamine agonist and experiencing wearing-off motor fluctuations. Patients were randomized in a 3 : 2 ratio to entacapone 200 mg or placebo, administered with each dose of levodopa. Efficacy was judged on the improvement of "on" and "off" time while awake (Patient Diary and UPDRS part IV Item 39), Investigators' Global Assessment, the SF-36 Health Survey, and changes in levodopa dosages. Patients were monitored for adverse events, laboratory safety and vital signs throughout the study. Improvements in "on" time as assessed using patient diary data showed a trend in favour of entacapone, however these did not reach statistical significance. "Off" time while awake (UPDRS part IV Item 39) showed an improvement of at least one category in 36% of entacapone-treated patients, compared with 22% in the control group (p = 0.0038). The proportion of patients showing an improvement at the Investigators' Global Assessment was significantly higher (p = 0.0006) in the entacapone-treated group of patients. Also, the proportion of patients with a reduction in their daily levodopa dose was significantly higher (p = 0.02) in the entacapone group (28%) compared with placebo (13%). As expected, the most frequent adverse events were dopamine-mediated (dyskinesia: entacapone 31% versus placebo 13%), and harmless urinary discoloration. The modest increase in dyskinesias could be readily managed by levodopa down-adjustment, and, at study end there was no significant difference for the UPDRS "overall dyskinesia score" between entacapone and placebo. In conclusion, although the primary efficacy variable did not reach statistical significance, the present results demonstrate that entacapone provides additional antiparkinsonian benefits to levodopa therapy and is well tolerated in levodopa-treated PD patients experiencing wearing-off motor fluctuations despite adjunct dopamine agonist therapy.

[Rivastigmine in current clinical practice in patients with mild to moderate Alzheimer's disease]. / Utilisation de la rivastigmine en pratique médicale courante chez des patients ambulatoires présentant une maladie d'Alzheimer.

Six hundred and sixty nine out patients with mild to moderate Alzheimer's disease were enrolled by 193 French neurologists, psychiatrists and gerontologists. The patients, 38p.cent males and 62p.cent females with a mean age of 75 years were progressively titrated from 3 to 12mg by day of rivastigmine, Exelon((R)), a day, and treated for 6 months. Mean Mini-Mental State (MMS) at baseline was 18.6. Concomitant pathologies and treatments were present in 89p.cent of the patients. Safety was good though 86p.cent reported an adverse event which was mild in most of the cases. The premature drop out rate was 29p.cent. Seventy-five patients showed no change or an improvement in their 4 Instrumental Activities of Daily Living (IADL) score with no change in the MMS at the end of treatment (18.8). Four items of the Neuro-Psychiatric Inventory (NPI): delusions, anxiety, apathy, and irritability were significantly improved at week 12 and the improvement in anxiety was still significant at the end of treatment. The total score frequency X severity showed a tendency to improvement. The correlations between the sum of the 4 IADL, MMS and NPI scores were strongly significant.

Rapid onset of bronchodilation in COPD: a placebo-controlled study comparing formoterol (Foradil Aerolizer) with salbutamol (Ventodisk).

Formoterol fumarate is a beta2-agonist bronchodilator that combines a fast onset of action with a long duration of action. Its fast onset of action is well documented in asthma but has not been directly compared with that of salbutamol in patients with chronic obstructive pulmonary disease (COPD). This randomized, double-blind, placebo-controlled study was conducted to assess the bronchodilatory effects over the first 3 h after inhalation of single doses of formoterol 24 microg delivered via the Aerolizer dry powder inhaler device (double-blind), or salbutamol 400 microg delivered by a Diskhaler dry powder inhaler (single-blind) in patients with COPD. A total of 24 patients with COPD were randomized [mean age 61.6 +/- 7.8 years, mean forced expiratory volume in 1 sec (FEV1) 1.38 +/- 0.32 l and 45.8 +/- 9.6% of predicted]. Inhalation of formoterol or salbutamol resulted in similar increases in FEV from 0 to 3 h post-dose. Both drugs produced similar bronchodilation by 5 min, which became almost maximal by 30 min. The primary efficacy variable, the area under the curve (AUC) of the FEV increase above predose baseline from 0 to 30 min (AUC(0-30 min)), demonstrated significant effects for formoterol (mean 5.89 +/- 4.67 l min(-1)), and salbutamol (mean 6.06 +/- 4.34 l min(-1)), which were not statistically different from each other but statistically significantly higher (P<0.0001) than that observed with placebo (-0.32 +/- 2.59 l min(-1)). In addition, both formoterol and salbutamol produced similar and rapid increases in forced vital capacity (FVC). In summary, this study confirms the rapid onset of action of formoterol and indicates that the onset of action of formoterol and salbutamol are similar in patients with COPD.

A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.

OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.

Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study.

Entacapone is a potent, reversible and orally active inhibitor of catechol-O-methyltransferase. This open multicenter study evaluated the efficacy, safety and tolerability of entacapone as adjunct therapy to levodopa/dopa decarboxylase inhibitor (> or = 3 daily doses) in patients with idiopathic Parkinson's disease and end-of-dose motor fluctuations. The 8-week study included 489 patients under conditions of typical daily medical practice. Patients were treated with a 200-mg fixed dose of entacapone administered with each scheduled dose of levodopa to a maximum of 10 doses per day. Other antiparkinsonian medication should have been stable for at least 1 month. The primary efficacy criteria were: (1) Part II (activities of daily living, ADL) of the Unified Parkinson's Disease Rating Scale (UPDRS), (2) the reduction of 'off' time during the daily waking period as assessed by the percentage of patients improving by at least one category at Item 39 of Part IV of the UPDRS. Secondary outcome measures included: (1) the investigator's global assessment of change, (2) quality of life (QoL) was assessed using the Parkinson's Disease Questionnaire (PDQ-39). Adverse events, vital signs and liver enzymes were monitored at weeks 2 and 8. The baseline mean score for ADL was 10.5 (+/-7.04), which decreased to 8.5 (+/-6.37) at the end of the study (p < 0.0001). Compared to baseline, 40.8% of patients experienced a reduction in 'off' time during the waking period; this improvement was highly significant (p < 0.0001). A reduction in the daily dose of levodopa was observed in 35.8% of patients (mean decrease 209 +/- 149 mg). QoL was improved by a mean of 10% in all categories of the PDQ-39 (p < 0.001), except social support and cognition. This improvement was statistically significant (p < 0.001). The dyskinesia score (UPDRS Item 32) was decreased significantly from 2.3 to 2.1 from baseline to end of study (p < 0.001), although 52.7% of patients reported levodopa-induced dyskinesia as an adverse event. There was no case of increased liver enzymes. The study results confirm that the excellent risk/benefit ratio seen in phase III controlled studies can be seen in daily neurological practice. Moreover, the study suggests that the benefits of entacapone are associated with a significant improvement in QoL.

Comparison between formoterol 12 microg b.i.d. and on-demand salbutamol in moderate persistent asthma.

Inhalation of on-demand salbutamol (ODS) several times daily is sometimes the only beta2-agonist prescribed in moderate persistent asthma, whereas a long-acting beta2-agonist should be added. This trial aimed to compare the efficacy of formoterol dry-powder capsule 12 microg b.i.d. (Foradil) and ODS in patients with moderate persistent asthma treated with inhaled corticosteroids, in the conditions of real practice. Two hundred and fifty-nine patients were randomized (formoterol; 130; ODS: 129) in this open, parallel-group trial. The mean increases in morning peak expiratory flow (PEF primary variable) and evening PEF over the 3-month treatment period were statistically significantly higher with formoterol: +25.7 and +24.1 l min(-1), respectively vs. +4.5 and +0.5 l min(-1) respectively with ODS. The increase in FEV1 was statistically significantly higher with formoterol at months 1 and 3. Formoterol reduced the use of salbutamol as rescue medication by two-thirds. The percentages of symptom-free days and nights statistically significantly increased with formoterol (+20% and +33% respectively), but did not significantly change with ODS. Clinically relevant and statistically significant improvement in the mean total score of the St George's Hospital Respiratory Questionnaire was observed in the formoterol group. Adverse events were similar in the two groups. The results show that treatment with formoterol has significant advantages over ODS in patients with moderate persistent asthma.

[Tolerance to valsartan in office practice in 3,197 hypertensive patients (the VALSE study)]. / Etude de la tolérance du valsartan en cardiologie de ville chez 3197 hypertendus (étude VALSE).

Valsartan, an angiotensin II antagonist with a potent and highly selective effect on AT1 receptors, has been found effective and safe in several randomized, controlled studies versus a placebo, other antihypertensive agents, or other angiotensin II antagonists. An eight-week, open-label, multicenter, prospective, pragmatic, phase IV trial was conducted by office-based cardiologists to evaluate the clinical safety and efficacy of valsartan 80 mg in everyday practice. The efficacy analysis included 3084 patients given valsartan alone for four weeks then, during the next four weeks, either valsartan alone or, if the diastolic blood pressure was still > or = 90 mmHg, valsartan in combination with another antihypertensive agent. The valsartan dosage was 80 mg/day. On day 28, 64% of patients were controlled and 78% were responders. The safety analysis included 3,108 patients. Of the 239 medical adverse events ascribed by the investigators to the study treatment, 72 led to premature study discontinuation. This figure translated into a 2.68% rate among treated patients, which is similar to the 2.3% rate recorded during the placebo-controlled trials performed as part of the valsartan clinical development program. These results confirm the outstanding safety profile of valsartan.

[The risk/benefit ratio of low-dose cyclosporin in the treatment of severe rheumatoid arthritis]. / Etude du rapport efficacité/tolérance de la ciclosporine à faibles doses dans le traitement de la polyarthrite rhumatoide sévère.

Although the efficacy of cyclosporine therapy in rheumatoid arthritis has been established, there have been no long term studies of the risk/benefit ratio of cyclosporine A in severe rheumatoid arthritis. A prospective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration, 11 years) with rheumatoid arthritis. Mean number of previous second-line treatments was four and 69% of patients had failed methotrexate therapy. The initial dosage of cyclosporine was 3 mg/kg/d and was increased if needed up to 5 mg/kg/d. The dosage was reduced in the event of serum creatinine elevation (by more than 30% versus baseline) or diastolic blood pressure elevation (above 95 mmHg). The statistical analysis was performed on an intention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were seen in all the clinical efficacy parameters. The mean reduction in corticosteroid dosage was 0.5 mg/d. The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 because of inefficacy). Twelve of the 56 patients with serum creatinine level elevation on at least one occasion and seven of the 35 patients with diastolic blood pressure elevation were taken off the study drug.

[Parlodel in early combination with levodopa in the treatment of Parkinson disease. Comparison of 2 dosage forms]. / Introduction du Parlodel en association précoce à la lévodopa dans le traitement de la maladie de Parkinson. Comparaison de deux progressions posologiques.

In order to compare two titrations of Parlodel in early combination with levodopa in the treatment of Parkinson's disease a multicentre randomized open study was performed with a fast titration in group A (15 mg/day for 3 weeks) and slow in group B (15 mg/day for 5 weeks). 153 patients were included: 77 in group A and 76 in group B. The recommended titration was observed in 76% in group A and 88% in group B, the difference was not significant. The efficacy assessed by the Webster Scale was remarkable and similar in the two groups. This study confirms the additive benefit of bromocriptine on the symptoms and long term complications of levodopa therapy, but no absolute conclusion can be drawn regarding the best titration.

IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study.

OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.

[Clozapine (Leponex) in France]. / La clozapine (Leponex) en France.

Leponex (clozapine) is an atypical neuroleptic indicated in severe schizophrenia, launched in France in December 1991. The safety and efficacy data pertaining to 1,062 patients treated on a compassionate needs basis between May 1989 and December 1991 constitute the first French experience on the drug. The results of an interim analysis pertaining to 602 patients, i.e. available data on 03-15-1992, generally collected on a retrospective basis, by means of a specific questionnaire are reviewed. The population included patients with severe and long-standing schizophrenia i.e. 15.71 +/- 9.3 years, resistant to usual neuroleptic therapy (90.86% of cases), and rarely with a history of intolerance to this class (2.49%). The indication was in the majority of the cases a paranoid schizophrenia (67.2%). The mean maintenance daily dose was 419 mg/d (+/- 152). Overall, with respect to associated drugs, neuroleptics were recorded in 16.4%, another psychotropic drug in 44.7% and symptomatic treatments for extrapyramidal disorders in 21.3% of patients. Of interest is the fact that, for those patients started on Leponex more recently, the drug is more often prescribed on a single basis. Leponex was stopped in 24.3% for the following reasons: adverse events 10.6%, lack of efficacy 6%, non compliance 3.8%, other reasons 3.8%. The adverse event profile is consistent with the literature data, taking into account the fact that certain adverse events were more commonly described: fatigue of lower limbs 11.8%, leucocytosis 19.8% and eosinophilia 4.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicardipine in the prevention of spasm-induced neurological deficits after subarachnoid hemorrhage: a dose-ranging study.

The tolerability of four doses of intravenous nicardipine (0.03, 0.08, 0.11, and 0.15 mg/kg/h) was assessed in this randomized multicenter, parallel-group study. Fifty-two patients with Hunt and Hess grade I-III aneurysmal subarachnoid hemorrhage were treated with intravenous nicardipine beginning within 4 days of bleeding, for a mean duration of 12.6 days; this treatment was followed by administration of oral nicardipine 90-120 mg until day 30. Hypotension was the main side effect, and it occurred only in the two groups that received the highest doses. However, it was possible to continue nicardipine in all cases at lower doses or even without modification, and hypotension was never responsible for any deleterious clinical effect.