Cessation Of Long-term Therapy Research Articles

Clinical and Radiological Disease Reactivation After Cessation of Long-Term Therapy With Natalizumab

ABSTRACTNaitalizumab is a potent monoclonal antibody approved for the treatment of relapsing–remitting multiple sclerosis (MS); however, little is known about the course of disease after cessation of therapy. The few existing reports describe different courses of disease after treatment discontinuation. Here we report on four MS patients who experienced clear clinical and radiological reactivation of the disease several months after cessation of therapy with natalizumab (15–29 months). In all cases, there was almost no clinical or radiological disease activity during natalizumab therapy. Three patients experienced a severe clinical relapse between 3 and 9 months after therapy cessation. The fourth patient developed cerebral magnetic resonance imaging (MRI) activity showing multiple new gadolinium-enhanced lesions. Due to these observations, it is recommended to weigh up the risk of disease reactivation against the risk of progressive multifocal leukoencephalopathy.

Platelet Function Analysis with PFA-100® in Patients Medicated with Acetylsalicylic Acid Strongly Depends on Concentration of Sodium Citrate Used for Anticoagulation of Blood Sample

Our data from 214 patients after cessation of long-term therapy with 100 mg/d ASA demonstrate that the determination of platelet-related primary hemostasis in citrated whole blood with PFA-100 is a reliable and sensitive method for the detection of ASA-induced platelet dysfunction. However, the sensitivity of the method is strongly dependent on concentration of sodium citrate used as anticoagulant. The results of PFA-100 testing show a clearly enhanced sensitivity for ASA when blood samples were collected with 0.129 M rather than 0.106 M sodium citrate. According to sample stability, PFA-100 results can only be confirmed up to 1 hour postcollection when blood was anticoagulated with 0.129 M but not with 0.106 M sodium citrate. Therefore, we recommend that testing with PFA-100 in patients with suspected ASA-induced platelet dysfunction should be performed exclusively in blood collected in buffered 0.129 M sodium citrate.

Pharmacokinetics and drug interactions of etretinate and acitretin

Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years.

Redevelopment of essential hypertension after cessation of long term therapy; preliminary findings.

We have previously found that the vascular hypertrophy that accounts for the maintenance of a substantial fraction of the elevation of the total peripheral resistance index (TPRI) in essential hypertension can be almost completely reversed by one years antihypertensive treatment (1). On ceasing treatment, blood pressure returns rapidly to pretreatment values suggesting that the original cause of the hypertension is still present. In the present study, 7 patients stopped a standard regimen for 10 weeks after at least 2 years of normotension. In the first week, standing and lying blood pressure increased related to rise in supine cardiac index and TPRI. Thereafter standing pressures, supine systolic blood pressure and cardiac index (CI) increased further, but supine diastolic blood pressure and TPRI did not alter. Changes in measurements of resting sympathetic activity, plasma volume or renin-angiotensin did not account for these observations. The return of hypertension after stopping effective therapy has some features previously described in borderline hypertension, particularly increasing systolic blood pressure, CI and postural blood pressure responses. Some of the changes may reflect the relative preponderance of cardiac and vascular amplifiers.

Withdrawal of long-term therapy with atenolol in hypertensive patients.

1 The offset of effects on blood pressure and heart rate after cessation of long-term therapy (19 +/- 3.6 months) with atenolol (200 mg once/daily) was studied in six hypertensive patients. 2 Withdrawal of atenolol resulted in a gradual return of lying, standing and post-exercise systolic and diastolic blood pressure levels and heart rate towards the baseline value. The offset of effect greatly exceeded the time for elimination of atenolol. 3 No significant differences in the pharmacokinetic profile of atenolol were evident between the values obtained following chronic dosing and an acute single-dose study. 4 The lack of clinical evidence of increased cardiac adrenergic sensitivity or rebound hypertension following withdrawal of atenolol contrasts with reports of a withdrawal syndrome following cessation of therapy with propranolol. Nevertheless until the mechanism of the propranolol-withdrawal syndrome is better understood caution is required when stopped therapy with atenolol in patients with severe coronary artery disease.