Withdrawal Of Maintenance Therapy Research Articles

Эффективность эзофагопротекции при коротких периодах отмены поддерживающей терапии ингибиторами протонной помпы у пациентов с пищеводом Баррета

Aim. Evaluation of the effectiveness of esophagoprotection in covering up short periods of withdrawal of maintenance therapy with proton pump inhibitors (PPIs) in patients with Barrett's esophagus (BE). Materials and methods. A retrospective analysis of the data of patients with histologically verified BE who received outpatient PPI therapy for at least 12 months was carried out. This cohort was divided into two groups to compare depending on the treatment regimen received. The first group included only patients who take PPIs constantly, while the second group included patients who had periodic interruptions in taking PPIs. In the second group, we analyzed only cases where to cover up the periods of PPI withdrawal the patients used the esophagoprotector Alfasoxx (10 ml 4 times a day, after each meal and at night). In the cohort, demographic data (age, gender), risk factors, length of the BE segment, degree of dysplasia, number of relapses of erosive esophagitis, and the data of high-resolution manometry on movement disorders of the thoracic esophagus (ineffective motility and lack of contractility) were analyzed. Results. The study included 39 patients (28 men and 11 women) with histologically verified BE. The average age was 57,1538 years (95% confidence interval 53.4269–60.8808). The gender structure was dominated by men (n=28). The duration of BE history in the analyzed cohort was 5.6769 years (95% confidence interval, 4.6161–6.7378). The first group consisted of 23 patients who take PPIs constantly. The second group consisted of 16 patients who had periodic interruptions in taking PPIs, which were covered by the esophagoprotector Alfasoxx. In the analyzed cohort, there were no significant differences between the groups in the average length of the BE segment, the number of patients with a long BE segment, the degree of dysplasia, the number of relapses of erosive esophagitis, and the rate of movement disorders of the thoracic esophagus. Conclusion. In routine practice, there are reasons for the temporary withdrawal of PPIs in patients with BE, which requires the administration of course esophagoprotection to cover up the risks. The results of this retrospective comparative study demonstrate the effectiveness of this strategy.

Atteintes rénales du lupus

Systemic lupus erythematosus is the most characteristic of auto-immune disorders that can lead to tissue damage in many organs, including kidney. Lupus nephritis occurs in 10 to 40% of lupus patients. Its clinical hallmark is the appearance of a proteinuria as soon as a 0.5 g/g or 0.5 g/d threshold, which calls for a renal histological evaluation in order to determine the lupus nephritis severity and the need for specific therapy. More than half of renal biopsies lead to the diagnosis of active lupus nephritis–class III or class IV A according to the ISN/RPS classification–that are the most severe in regards to renal prognosis and mortality. Their treatment aims to their clinical remission and to the prevention of relapse with minimal adverse effects for eventually the preservation of renal function, the prevention of other irreversible damage, and the reduction of risk of death. The remission is obtained through induction therapies of which the association of high dose steroids and cyclophosphamide is the most experienced. When this association must be challenged by the prevention of side-effect, in particular infertility, mycophenolate can be given instead of cyclophosphamide. Maintenance therapy, for the prevention of relapse, consists in mycophenolate or in azathioprine, mycophenolate being the most efficient however associated with a high risk of teratogenicity. Withdrawal of maintenance therapy is possible after two to three years in absence of high risk factors of relapse of lupus nephritis, however a reliable assessment of the risk of relapse is still lacking. Only pure membranous lupus nephritis (pure class V) associated with high level proteinuria requires specific therapies that usually associates steroids and an immunosuppressive drug. However, their choice hierarchy and even the use of less immunosuppressive strategies remain to be determined in terms of benefice over risk ratios. In spite of its trigger effect on lupus activity, pregnancy can be safe and successful if scheduled in the lowest risk periods with close multidisciplinary monitoring before, during and after. When necessary, renal replacement therapy does not require specific adaptation, renal transplantation is the best option when possible, as early as possible.

A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy

One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.

Outcomes 7 Years After Infliximab Withdrawal for Patients With Crohn’s Disease in Sustained Remission

Little is known about long-term outcomes of patients with Crohn's disease (CD) after infliximab withdrawal. We aimed to describe the long-term outcomes of patients with CD in clinical remission after infliximab treatment was withdrawn. We performed a retrospective analysis of data from the 115 patients included in the infliximab discontinuation in patients with CD in stable remission on combined therapy with antimetabolites (STORI) study, performed at 20 centers in France and Belgium from March 2006 through December 2009. The STORI cohort was a prospective analysis of risk and factors associated with relapse following withdrawal of maintenance therapy with infliximab, maintained on antimetabolites, while in clinical remission. We collected data from the end of the study until the last available follow-up examination on patient surgeries, new complex perianal lesions (indicating major complications), and need for and outcomes of restarting therapy with infliximab or another biologic agent. The de-escalation strategy was considered to have failed when a major complication or infliximab restart failure occurred. Of the 115 patients initially included, data from 102 patients (from 19 of the 20 study centers) were included in the final analysis. The median follow-up time was 7 years. Twenty-one percent of the patients did not restart treatment with infliximab or another biologic agent and did not have a major complication 7 years after infliximab withdrawal (95% CI, 13.1-30.3). Among patients who restarted infliximab, treatment failed for 30.1% 6 years after restarting (95% CI, 18.5-42.5). Overall, at 7 years after stopping infliximab therapy, major complications occurred in 18.5% of patients (95% CI, 10.2-26.8) whereas 70.2% of patients had no failure of the de-escalation strategy (95% CI, 60.2-80.1). Factors independently associated with major complications were upper-gastrointestinal location of disease, white blood cell count ≥ 5.0× 109/L, and hemoglobin level ≤12.5 g/dL at the time of infliximab withdrawal. Patients with at least 2 of these factors had a more than 40% risk of major complication in the 7 years following infliximab withdrawal. In a long-term follow-up of the STORI cohort (7 years) one fifth of the patients did not restart infliximab or another biologic agent and did not develop major complications. Seventy percent of patients had no failure of the de-escalation strategy (no major complication and no failure of infliximab restart).

Persisting Bone Marrow Aplasia Following Interferon-Alpha Combined with Ara-C for Chronic Myelogenous Leukemia

A 37-year-old man with a newly diagnosed chronic myelogenous leukemia received induction therapy with hydroxyurea and interferon-alpha, and maintenance therapy with low-dose ara-C and interferon-alpha. Subsequent to a rapid hematological remission, a continuously aggravating pancytopenia with bone marrow aplasia developed which persisted after withdrawal of maintenance therapy. Bone marrow examination exhibited aplastic areas and residual hematopoiesis with impaired maturation; cytogenetically, there was a 100% persistence of Philadelphia chromosome-positive metaphases. By allogeneic bone marrow transplantation, a complete reconstitution of hematopoiesis was achieved.

Adrenalectomy of the Calf and Its Effects on Various Blood Constituents

Summary Surgical adrenalectomy was successfully performed in calves without suturing the wall of the vena cava, by using a special forceps to facilitate removal of the gland. Maintenance of adrenalectomized calves was possible under controlled conditions, with the intramuscular injection of 25mg. cortisone acetate or 5mg. prednisone plus 5mg. desoxycorticosterone acetate per 100lb. body weight, daily or every other day. Calves were also maintained in an apparently normal state without steroid therapy by the free-choice feeding of salt, which was consumed at a rate about four times that of the normal calf. The outward symptoms of adrenal deficiency, manifested during the period when no therapy was given, began with lethargy and weakness in the legs. This was followed by anorexia, extreme apathy, a completely prostrate position, and extreme depression and arrhythmia of the heart beat shortly before death ensued. Loose, foul-smelling feces and a rapid, labored respiration were sometimes observed. The calves survived about six to seven days following withdrawal of maintenance therapy. In three adrenal-deficient calves there was a decrease in the serum Na:K ratio, a decrease in serum chlorides, and an increase in serum potassium, all of which were highly significant (P less than 0.01). In two of the three animals there was a reduction in serum sodium, total neutrophils, and mature neutrophils, and an increase in RBC and eosinophils. The influence of adrenalectomy on serum calcium, blood hemoglobin, hematocrit, and neutrophil levels varied considerably between calves. No significant differences were found in WBC, lymphocyte, and monocyte levels following adrenalectomy. One calf was found to have an adrenal remnant which prevented it from succumbing completely to the effects of adrenalectomy.