Can mycophenolate mofetil be tapered safely in myasthenia gravis? A retrospective,multicenter analysis

Introduction: Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well‐controlled patients. Methods: This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed. Results: Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months). Conclusions: Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended. Muscle Nerve 52 : 211–215, 2015     

Blood Pressure and Metabolic Effect of a Combination of Lercanidipine with Different Antihypertensive Drugs in Clinical Practice

The aim of this study is to assess the blood pressure (BP) and metabolic effects of lercanidipine when combined with other classes of first-line antihypertensive drugs in day-to-day clinical practice. For this study, we consecutively enrolled 162 patients with uncomplicated primary hypertension, who are partial responders to the treatment with lercanidipine over a period of 24 months. Patients were then allocated to the combination of lercanidipine (10–20 mg/day) with β-blockers, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor blockers according to compelling indications (if any) and/or suggestions of European Society of Hypertension–European Society of Cardiology (ESH–ESC) guidelines. All the enrolled patients completed the study and no adverse drug reaction was registered during the research period. The association of a second drug with lercanidipine determined an additional BP decrease of either systolic BP or diastolic BP independently from the type of drug added (P always <.05). The additional effect of lercanidipine appears widely distributed with no significant differences in the size of BP decrease. From the metabolic point of view, the addition of a second drug did not determine a significant variation in the serum levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (P always >.05). Conversely, a significant decrease in fasting plasma glucose and serum levels of triglycerides has been observed in patients where lercanidipine has been combined with an angiotensin-converting enzyme inhibitor or an angiotensin-II receptor blocker. In conclusion, in our study we observed that lercanidipine-based protocols are well tolerated and efficacious in reducing BP. Moreover, the association of lercanidipine with renin–angiotensin system blockers is also associated with significant improvements in triglycerides and fasting plasma glucose.     

Azathioprine-cyclosporin A (CyA) double therapy versus CyA alone after the first rejection episode in kidney-transplanted patients under CyA: A randomized study

Abstract. A controlled trial was carried out in 78 kidney transplant recipients under cyclosporin A (CyA) monotherapy who had experienced a first rejection episode. Thirty-nine were randomly selected to receive azathioprine (AZA; 2 mg/kg per day) in combination with CyA (group AZA+), while the others continued to receive CyA alone (group AZA"). Four of the patients in the study died; three were in group AZA +the cause of their deaths was cardiovascular. Graft survival rates were 97% at 6,12, and 24 months postrejection in group AZA+as compared to 97%, 90%, and 81%, respectively, in group AZA" ( P < 0. 05 at 12 and 24 months). Significantly more patients were free of rejection with the double therapy than with CyA monotherapy (75% vs 51% at 12 months; P < 0. 05). In spite of the addition of a second immunosuppressive drug, the CyA dosages given and the CyA trough blood levels maintained were similar in the two groups. Serum creatinine was similar in patients with and without AZA. Infectious complications were also similar in both groups. A significant macrocytosis was the only side effect of AZA therapy. On the whole, these data show the benefit of CyA-AZA double therapy in the prevention of rejection recurrence without exposing patients to either increased risk of infection or serious side effects of AZA. Whether this double therapy should be systematically administered to all recipients or only after a first rejection episode is discussed.     

Time course of physical and psychological responses to selegiline monotherapy in newly diagnosed,idiopathic parkinosonism

Rationale: Poor specificity of face-value endpoints and the poor sensitivity of gross clinical examination may have militated against demonstrating prophylaxis by selegiline. Methods: Objective measures of the four cardinal signs were used as primary outcome criteria in a randomised, double-blind, placebo-controlled, parallel group study of selegiline monotherapy in 25 newly diagnosed elderly sufferers from idiopathic parkinsonism, stratified for sex and Hoehn and Yahr functional staging. Results: There was a significant interaction between time and nature of treatment with respect to rigidity. The effect of time during active treatment was highly significant: rigidity decreased by 1.3 % per week. The worsening of rigidity on placebo was not statistically significant. Neuronal rescue is a possible explanation for the long term, progressive improvement produced by selegiline. No significant treatment effect was seen on the other cardinal signs. However, there was a significant quadratic time trend for arousal on active treatment suggesting tolerance to this effect. Conclusion: The difference in time course between the psychostimulant and physical effects suggests more than one mode of action. Received: 7 December 1994 /Accepted in revised form: 12 September 1995     

Comparing the Cognitive Effects of Phenytoin and Carbamazepine in Long-Term Monotherapy: A Two-Year Follow-Up

Summary: We compared the cognitive effects of randomly prescribed phenytoin (PHT) and carbamazepine (CBZ) therapy on newly diagnosed patients with epilepsy in a 2–year parallel group follow-up study. Fifteen patients were receiving PHT and 16 were receiving CBZ. Neuropsychological assessements were conducted before the treatment and after 6 and 24 months of steady-state drug therapy. Differential effects of PHT and CBZ during follow-up were observed in 3 of 32 measurements. PHT appeared to have negative effects on visually guided motor speed of both hands. In addition, the performance of the PHT group as compared with the CBZ group developed less positively in one visual memory task. The development of mood, as measured by Profile of Mood States (POMS), was quite similar in both drug groups; Tension, Depression, and Bewilderment decreased and Vigor increased during the follow-up. The results suggest that the long-term effects of PHT as compared with thoseof CBZ on cognition are few and restricted mainly to some visually guided motor functions. The effects of PHT on cerebellar function as a possible mechanism for these changes is discussed.     

Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.

Piribedil is a D2 dopamine agonist, which has been shown to improve symptoms of Parkinson's disease (PD) when combined with L-dopa. The objective of this study was to compare the efficacy of piribedil monotherapy to placebo in patients with early PD over a 7-month period. Four hundred and five early PD patients were randomized (double-blind) to piribedil (150-300 mg/day) or placebo. L-dopa open-label supplementation was permitted. Unified Parkinson Disease Rating Scale part III (UPDRS III) score as the last observation on monotherapy over 7 months was the primary outcome measure. Secondary outcomes were proportion of responders (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months, UPDRS III subscores, and UPDRS II. UPDRS III improved on piribedil (-4.9 points) versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% CI = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher for piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P < 0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II improved on piribedil by -1.2 points, while it deteriorated by 1.5 points on placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion of patients remaining on monotherapy after 7 months was greater in the piribedil group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that reported for other dopamine agonists, gastrointestinal side effects being the most common (22% of patients in piribedil group vs. 14% on placebo). Piribedil is effective and safe as early PD therapy.     

Clonazepam monotherapy for epilepsy in childhood

Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +/- 0.021 mg/kg/day in infants and 0.057 +/- 0.022 mg/kg/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%.     

Tolerability, efficacy and pharmacokinetics of bicalutamide 300 mg, 450 mg or 600 mg as monotherapy for patients with locally advanced or metastatic prostate cancer, compared with castration

OBJECTIVE: To evaluate the pharmacokinetics, tolerability and effect on endocrinology of bicalutamide given as once-daily monotherapy at doses of >150 mg to patients with locally advanced (M0) or metastatic (M1) prostate cancer, with efficacy as a secondary endpoint. PATIENTS AND METHODS: Patients were initially enrolled to receive bicalutamide 300 mg in a non-randomized phase, after which further patients were randomized to higher bicalutamide doses (in 150 mg increments) or castration. Overall, 248 patients received bicalutamide at 300 mg (21), 450 mg (95) or 600 mg (42), or castration (90). RESULTS: Systemic exposure to bicalutamide stabilised at a dose of approximately 300 mg, as determined by pharmacokinetic analysis. The tolerability of high doses of bicalutamide was similar to that of the 150 mg dose, with no increase in the incidence of adverse events. Patients receiving bicalutamide had early increases in the mean levels of oestradiol, testosterone and luteinizing hormone, which were maintained throughout the study. Levels of these hormones rapidly decreased in the castration group and remained low. From baseline (first day of treatment) to 12 weeks there was an equivalent reduction in prostate-specific antigen (PSA) levels across all four groups. At a median follow-up of 5 years, there was no significant survival difference between patients who received bicalutamide and those who received castration, either in M0 or M1 disease. CONCLUSION: The low median PSA level (180 ng/mL) of patients with M1 disease might account for the lack of survival difference between the treatment groups. Further studies are needed to assess whether high-dose bicalutamide monotherapy can provide equivalent efficacy to castration in patients with M1 prostate cancer.     

Empiric Treatment of Localized Infections in the Febrile Neutropenic Patient with Monotherapy

Empiric therapy is necessary for febrile, neutropenic patients in order to minimise morbidity and mortality. Certain agents are now available for monotherapy which offcrcomparable success to combinations of either an aminoglycoside with a β-lactam or two β-lactams. However, no regimen offers complete treatment under all circumstances in all patients. It is also apparent that febrile, neutropenic patients comprise a more heterogeneous group than just those with bacteraemia, clinically apparent infection and unexplained fever. Localized infections occur in just under a third of cases at the onset of fever and a similar number will develop during the course of fever. Mortality is higher in infections that are accompanied by bacteraemia and also those that develop subsequently, especially when related to the lung. The aetiological agent also differs with each type of infection as does the duration of fever and symptoms. Consequently modifications are required more often. The length of treatment may also differ. Therefore, during the first 3-4 days of empiric therapy, every effort should be made to identify incipient localized infections in addition to detecting bacteraemia. Changes in therapy can then be based on objective grounds rather than continued fever offering more patients individual treatment than is possible when relying only on the temperature chart.     

Long-term effectiveness of luteinizing hormone-releasing hormone agonist or antiandrogen monotherapy in elderly men with localizect prostate cancer （T1-2） ： a retrospective study

Aim： To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs （luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen） that were used individually to treat patients with localized prostate cancer （T1-2） at our institution. Methods： Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer （T1-2） received either LHRH agonist （leuprolide acetate 7.5 mg/month） monotherapy （group 1, n = 62） or antiandrogen monotherapy （group 2, n = 35; 18 received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.i.d, and 4 received flutamide 250 mg t.i.d.）. The mean age in both groups was 76 years. Results： The mean follow-up time was （50.8 ±8.5） months in group 1 and （43.1 ± 2.2） months in group 2. Prostate-specific antigen （PSA） levels rose in only 1 of the 62 patients （1.6%） in group 1, and in 20 of the 35 patients （57.1%） in group 2. In group 2, 10 of the 20 patients （50 %） with increasing PSA levels were treated with LHRH salvage therapy, and eight （80%） responded. Hot flashes （54.8%） and lethargy （41.9%） were the most common side effects in group 1. In contrast, nipple-tenderness （40%） and light-dark adaptation （17.1%） were more often seen in group 2. Only 1 of the 62 patients （1.6%） in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients （22.9%） in group 2 did so. Conclusion： Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer （T1-2）. It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.