Pregnancy and Crohn's disease.

Crohn's disease commonly affects women of childbearing age. Available data on Crohn's disease and pregnancy show that women with Crohn's disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn's disease during pregnancy is similar to pharmacological therapy for non-pregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Most drugs, including sulfasalazine, mesalazine, corticosteroids, and immunosuppressors such as azathioprine and 6-mercaptopurine, are safe, whereas methotrexate is contraindicated.

Maintenance of remission in Crohn's disease.

When remission of Crohn's disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission.

Syndrome de Cogan : à propos d'un cas et brève revue de la littérature [Cogan's Syndrome]

We report the case of a 20-year-old woman, with no medical history, who in a short period of time developed the association of a bilateral vestibulocochlear deficit and a nonsyphilitic interstitial keratitis, the usual clinical presentation of Cogan's syndrome. This rare disease was named after David Cogan, the ophthalmologist to whom we owe the description of the first series of cases. The precise aetiology of Cogan's syndrome has yet to be defined, but clinical and biological evidence point toward an immunopathological process. Some authors distinguish between a typical and an atypical form of Cogan's syndrome, the former being associated with interstitial keratitis, the latter with other forms of ocular involvement. The diagnosis of Cogan's syndrome is mainly a clinical one, the association of a bilateral vestibulocochlear deficit and a non-syphilitic keratitis being almost specific. Cogan's syndrome is frequently associated with general signs and cardiovascular, neurological, rheumathological and digestive involvement. Laboratory data usually show nonspecific inflammatory signs (elevation of the white cell count and of the erythrocyte sedimentation rate). The mortality of the disease is essentially determined by its cardiovascular involvement, mostly aortic insufficiency, which should therefore actively be sought for in every patient. It is useful to emphasise that the typical form of Cogan's syndrome carries a higher risk regarding the development of aortic insufficiency, whereas the atypical form is more often associated with a systemic vasculitis. Treatment is mandatory, based upon corticosteroids, and must sometimes be intensified by the administration of a steroid-sparing immunosuppressive drug. Although our patient perfectly met the diagnostic criteria of Cogan's syndrome, the vestibular symptoms preceded the visual complaints, the reverse temporal sequence being more often reported in the literature. Systemic signs and cardiovascular involvement are frequently seen in Cogan's syndrome, but were notably absent in our patient. Blood samples showed inflammatory signs, whereas both lumbar puncture and cerebral MRI were normal, which is the usual pattern encountered in Cogan's syndrome. Following the rapid initiation of immunosuppressive therapy (Prednisone), the visual symptoms due to the bilateral keratitis resolved in a matter of days, whereas the vestibulocochlear deficit was only partly - but dramatically - reduced. This is in accordance with literature data, showing that a severe and permanent auditory deficit occurs at some time in the majority of patients suffering from Cogan's syndrome. Tapering off Prednisone unfortunately reactivated the audiovestibular and ocular symptoms of the disease in our patient so that a steroid-sparing immunosuppressive drug had to be added (azathioprine, followed by mycophenolate mofetil because the patient developed hepatic intolerance). Only after these therapeutic measures could the disease be stabilised. With this case report, we would like to emphasise the importance of rapidly identifying the clinical picture of Cogan's syndrome, so that immunosuppressive therapy can be started without delay, which may significantly reduce both morbidity and mortality of this disease.

Unsatisfactory outcomes in myasthenia gravis: influence by care providers.

Myasthenia gravis (MG) can be difficult to treat despite an available therapeutic armamentarium. Our aim was to analyze the factors leading to unsatisfactory outcome (UO). To this end we used the Myasthenia Gravis Foundation of America classification system. Forty one patients with autoimmune MG were followed prospectively from January 2003 to December 2007. Outcomes were assessed throughout follow-up and at a final visit. 'Unchanged', 'worse', 'exacerbation' and 'died of MG' post-intervention status were considered UOs. During follow-up, UO rates reached 54% and were related to undertreatment (41%), poor treatment compliance (23%), infections (23%), and adverse drug effects (13%). The UO rate at final study assessment was 20%. UO during follow-up was significantly (P = 0.004) predictive of UOs at final assessment. When care was provided by neuromuscular (NM) specialists, patients had significantly better follow-up scores (P = 0.01). At final assessment UO rates were 7% and significantly better in patients treated by NM specialists, compared to other physicians where UO rates reached 27%. UO was a frequent finding occurring in more than half our patients during follow-up. Nearly two-thirds of the UOs could have been prevented by appropriate therapeutic adjustments and improved compliance. The differential UO rates at follow-up, their dependency on the degree to which the management was specialized and their correlation with final outcomes suggest that specialized MG care improves outcomes.

Exposition aux immunosuppresseurs in utero [Exposure in utero to immunosuppressives]

The number of pregnant women receiving immunosuppressive therapy is increasing. Use of immunosuppressants during pregnancy is indicated for anti-rejection therapy in transplantation patients and treatment of autoimmune diseases. Despite the maternal and fetal risks of these pregnancies, the proportion of surviving infants is improving and the possibility that a pregnancy could occur in these women during their childbearing years should be considered. All immunosuppressant drugs and their metabolites cross the placenta, raising questions about the long-term outcome of the children exposed to these agents in utera. There is no increased risk of congenital anomalies. However, there is an elevated incidence of prematurity, intrauterine growth retardation (IUGR) and therefore low birthweight, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporin, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes. The follow-up of these infants should be carefully organized and multidisciplinary, taking the perinatal context into account.

Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report.

INTRODUCTION: Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. CASE PRESENTATION: We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. CONCLUSIONS: Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

Stratégies thérapeutiques dans les myopathies inflammatoires [Therapeutic strategies in idiopatic inflammatory myopathies]

Idiopathic inflammatory myopathies, such as polymyositis and dermatomyositis, share common clinical features such as progressive, symmetrical muscle weakness prevailing in the lower limbs, associated sometimes with muscle pains. High CK and typical biopsy insure the diagnosis. Possible causes for secondary myopathies and associated diseases should be actively investigated. The search for autoantibodies helps to better classify inflammatory myopathies and to better define the prognosis of the myopathy. Glucocorticoids are the cornerstone of the early phase therapy. Glucocorticoid-sparing agents, such as azathioprine and methotrexate, are second line agents but can be readily prescribed. In case of therapeutic resistance, a rescue treatment (ciclosporine, immunoglobulins, rituximab, cyclophosphamide) could be considered.

Retrospective analysis of complications of immunosuppressive therapies (steroidsand immunosuppressive therapies) in pediatric uveitis

Purpose¦The purpose of this study is to analyze the incidence rate of side effects occurring during systemic therapy (corticosteroids, methotrexate, azathioprine, cyclosporine A or biologic agents) of auto-immune uveitis.¦Material and methods¦Retrospective study including 23 / 71 patients aged between 0-16 years old presenting with a chronic non-infectious uveitis. All children were treated in the Jules-Gonin Eye Hospital and paediatric rheumatology unit of the CHUV (Centre Hospitalier Universitaire Vaudois) between January 2000 and December 31st 2010. Side effects were reported as minor (without subsequent change in systemic medication), moderate (associated with a change in systemic dosage or class of immunosuppressive therapy or in the presence of Cushingoid face or weight gain) or severe (hospitalization or life threatening).¦Results¦52% of boys and 48% of girls are present in the cohort with a mean age at the first visit of 8.1 years (1.7-15.6). Intermediate uveitis consisted of the commonest aetiology with 8 patients (35%), juvenile idiopathic arthritis (JIA) in 7 (30%), Behçet's disease in 3 (13%) and others in 5 (22%). The overall length of therapy was longer for prednisone (26.6 ± 5.4 patient / year), but was similar between methotrexate (22.1 ± 5.4 patient / year) and azathioprine (15.2 patient / year). Moderate side effects were respectively 64% for corticosteroids therapy, 54% with methotrexate and 14% with azathioprine. One severe and one moderate side effect were observed with anti-TNFα respectively stage III anaphylactic shock and pain during injection associated with a redness of the site of injection and limping after the injection.¦Discussion¦Immunomodulating agents allow a rapid decrease in corticosteroid therapy, but one severe side effect was observed with anti-TNFa agents. These agents are considered in most countries as third line therapeutic agents.

Rituximab treatment in non-malignant inflammatory sensory polyganglionopathy

Non-malignant inflammatory sensory polyganglionopathy (NISP) is the most common form of acquired ganglionopathies, a rare and distinct subgroup of peripheral nerve diseases characterized by a primary degeneration of sensory neurons in dorsal root ganglia. There is a rational for the use of immune modifying agents (IMA) in NISP since an underlying auto-immune process is demonstrated or suspected. However, commonly used IMA such as corticosteroids, azathioprine, methotrexate or IVIG do not prevent disease's progression in the majority of patients. The use of newer IMA, especially those directed against B-cells, may be a therapeutic alternative. An interesting candidate is rituximab, a mouse-human chimeric anti CD20 antibody that specifically eliminates B-cells and B-cells precursors.Objectives: This is a prospective open label pilot study to determine the efficacy of rituximab treatment in NISP patients, who did not respond to commonly used IMA.Methods: Five patients (40% male) with a mean age of 55 years (range 49-67), diagnosed with NISP after extensive work-up, were treated (schema used for one cure: 2 9 1gr within 15 days interval). Neurological scores (NIS, ISSS, ODSS) and B cell counts were assessed at baseline and during clinical follow-up at 2 and 6 monthsto assess treatment efficacy.Results: The treatment was generally well tolerated. Minor adverse events reported were transient arterial hypotension during the infusions in two patients and intermittent mild leucopenia in one patient. Clinical evolution during the follow-up period was characterized by a stability of the functional scores in four patients (80%) and the continuation of disability progression of one patient (20%). CD4 cells disappeared in all patients after the second infusion, an effect that lasted until the follow up at 6 months.Conclusion: The preliminary results of this pilot study indicate that rituximab is generally well tolerated and prevents progression of disability during the 6-month observation period in NISP patients. Inclusion of additional patients and extending of the follow-up period are intended to further investigate the efficacy of rituximab in NISP.

Syndrome des anti-synthétases et tacrolimus: efficacité et tolérance, à propos de 2 cas

Introduction. - Le traitement de la polymyosite et de l'atteinte pulmonaireassociées au syndrome des anti-synthétases peut serévéler difficile. Le tacrolimus est proposé en cas d'échec aux autresimmunosuppresseurs. Néanmoins, contrairement aux patientsgreffés, son utilisation dans cette indication est mal codifiée. Nousrapportons les cas de 2 patients traités efficacement par tacrolimus.Cas Clinique. - Cas 1. Il s'agit d'un homme de 44 ans originaire deMadagascar, chez qui le diagnostic de syndrome des anti-synthétasesest posé devant l'association mains de mécanicien, polymyosite,manifestation de raynaud et présence d'anticorps anti Jo1fortement positifs à 281U (norme < 50U). Les différents traitementsproposés (prednisone 1 mg/kg, méthotrexate, azathioprine,rituximab et Immunoglobulines IV) ne permettent pas de contrôlerla situation avec un pic des CK à 24 000 U/l au décours des Ig IV.Une IRM réalisée alors retrouve une activité inflammatoire intensedes compartiments antérieurs et postérieurs des cuisses des 2 côtés.Finalement un traitement de tacrolimus est proposé en augmentationprogressive. L'efficacité du traitement est mesurée par l'évolutiondes CK qui passent en quelques mois de 24 000 U/l à 300 U/lsous une dose de 6 mg/j de tacrolimus et d'une amélioration parIRM spectaculaire. Malheureusement, suite à un épisode de déshydratation,le patient développe une insuffisance rénale aigüemodérée (créatinine à 124 _mol/l contre 89 auparavant) non réversibleaprès réhydratation. Pour stabiliser la fonction rénale le tacrolimusest baissé à 4 mg/jour au prix d'une réapparition des douleursmusculaires et d'une ré-ascension des CK à 1 000 U/l. Cas 2. Il s'agitd'une patiente de 61 ans chez qui le diagnostic de syndrome desanti-synthétases est posé devant l'association atteinte articulaire,mains de mécanicien, atteinte musculaire, pneumopathie interstitiellediffuse et forte positivité des Ac anti JO1 à 252 U. Une associationtacrolimus et prednisone est rapidement proposée en raison del'atteinte pulmonaire. Malheureusement la patiente développe uneinsuffisance rénale progressive sous 9 mg/j de tacrolimus et malgréune réponse favorable sur le plan pulmonaire, le traitement estinterrompu avec amélioration de la fonction rénale.Discussion. - Le tacrolimus est un traitement immunosuppresseuranalogue à la ciclosporine, avec une action 100 fois supérieure. Ilinhibe l'activation et la prolifération des cellules T et sa principaletoxicité est rénale. Traitement puissant, il a montré son efficacitédans les atteintes pulmonaires sévères liées à un syndrome desanti-synthétases1.2. Les pneumologues le connaissent bien et chezles patients greffés, la surveillance de l'efficacité et de la toxicité dutraitement se fait grâce à des mesures du taux résiduel. Néanmoinsdans le cadre du syndrome des anti-synthétases les mesures de surveillancesont moins bien codifiées. Même si l'efficacité du tacrolimussemble excellente dans les formes musculaires etpulmonaires sévères, nos 2 cas nous rendent attentifs sur l'importanced'une surveillance rapprochée de la fonction rénale.Conclusion. - Le tacrolimus est un puissant immunosuppresseur quipeut être proposé aux patients souffrant de manifestations sévèresd'un syndrome des anti-synthétases. Une dose standard n'existe paset il faut être attentif à sa toxicité rénale.

Fibrose pulmonaire idiopathique: nouveautés diagnostiques et thérapeutiques [Idiopathic pulmonary fibrosis: recent diagnostic and therapeutic advances].

Idiopathic pulmonary fibrosis (IPF) is the most frequent of the idiopathic interstitial pneumonias. It is a progressive disorderwith a poor prognosis. Its diagnosis requires the careful exclusion of potential causes, and a pattern of usual interstitial pneumonia at high-resolution computed tomography or video-assisted surgical lung biopsy. Several recent randomized trials have profoundly modified the therapeutic management of IPF. The combination of prednisone and azathioprine, often prescribed until recently, has been shown to be harmful and is no longer indicated. N-acetylcystein, also used in the past decade, failed to show an efficacy. However, two new antifibrotic drugs, pirfenidone and nintedanib, have for the first time proven effective in slowing disease progression.

Idiopathic recurrent neuroretinitis: effects of long-term immunosuppression.

OBJECTIVE: To determine the efficacy of long-term immunosuppressive therapy in patients with recurrent idiopathic neuroretinitis. METHODS: A retrospective review of 30 patients with recurrent idiopathic neuroretinitis identified 7 who received ongoing immunosuppression with prednisone and/or azathioprine for whom adequate follow-up information was available. We calculated the number of attacks per unit of time for each patient before and after treatment to derive mean attack rates for the group. RESULTS: For the entire group, we found a rate of 0.58 attacks per year prior to the initiation of immunosuppressive treatment, which decreased to 0.16 attacks per year following immunosuppression. This represents a reduction in the attack rate of 0.41, or a 72% decrease in attack frequency. CONCLUSIONS: Our study suggests a possible role for long-term immunosuppressive treatment in patients with recurrent idiopathic neuroretinitis. A longer follow-up interval, more standardized treatment regimens, and additional outcome measures might reveal a greater benefit of treatment.

Therapy of steroid-resistant inflammatory bowel disease.

Background and Aims: Although systemic corticosteroids are successfully administered for the induction of clinical response and remission in the majority of patients with inflammatory bowel disease (IBD) presenting with a flare, a proportion of these patients demonstrate a primary nonresponse to steroids or in the case of an initial response, they develop a resistance or a steroid dependence. Long-term therapy with corticosteroids for treatment of IBD should be avoided, given the high frequency of adverse treatment effects. Knowledge about treatment strategies in case of steroid nonresponse is therefore highly relevant. Methods: A systematic literature research was performed using Medline and Embase to summarize the currently recommended treatment strategies for steroid-resistant IBD. Results: Treatment of steroid-resistant Crohn's disease is based on the introduction of immunomodulators such as azathioprine, 6-mercaptopurine or methotrexate, the anti-TNF drugs infliximab, adalimumab and certolizumab pegol. In the case of steroid resistance in ulcerative colitis, aminosalicylates, the above-mentioned immunomodulators, infliximab, adalimumab or calcineurin inhibitors such as ciclosporin or tacrolimus may be administered. Conclusion: This review summarizes the current evidence for treating steroid-resistant IBD.

Appropriate maintenance treatment for Crohn's disease: results of a multidisciplinary international expert panel - EPACT II

Introduction: Biological. therapy has dramatically changed management of Crohn's disease (CD). New data have confirmed the benefit and relative long-term safety of anti-TNF alpha inhibition as part of a regular scheduled administration programme. The EPACT appropriateness criteria for maintenance treatment after medically-induced remission (MIR) or surgically-induced remission (SIR) of CD thus required updating. Methods: A multidisciplinary international expert panel (EPACT II, Geneva, Switzerland) discussed and anonymously rated detailed, explicit clinical indications based on evidence in the literature and personal expertise. Median ratings (on a 9-point scale) were stratified into three assessment categories: appropriate (7-9), uncertain (4-6 and/or disagreement) and inappropriate (1-3). Experts ranked appropriate medication according to their own clinical practice, without any consideration of cost. Results: Three hundred and ninety-two specific indications for maintenance treatment of CD were rated (200 for MIR and 192 for SIR). Azathioprine, methotrexate and/or anti-TNF alpha antibodies were considered appropriate in 42 indications, corresponding to 68% of all appropriate interventions (97% of MIR and 39% of SIR). The remaining appropriate interventions consisted of mesalazine and a "wait-and-see" strategy. Factors that influenced the panel's voting were patient characteristics and outcome of previous treatment. Results favour use of anti-TNF alpha agents after failure of any immunosuppressive therapy, while earlier primary use remains controversial. Conclusion: Detailed explicit appropriateness criteria (EPACT) have been updated for maintenance treatment of CD. New expert recommendations for use of the classic immunosuppressors as well as anti-TNF alpha agents are now freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Retrospektive Analyse der Mixantron-Behandlung bei Multipler Sklerose von Juli 2000 bis Juni 2007

Résumé :Introduction : La mitoxantrone est un anthracénédione cytostatique aux ef¬fets immunosuppresseurs et -modulateurs qui est administré entre autre dans les évolutions graves de la sclérose en plaques (SEP). Peu d'études concernant l'efficacité et la tolérance de la mitoxantrone ont été publiées. Un travail de re¬cherche statistique s'imposait en raison du nombre de patients souffrant de SEP traités par ce médicament dans le service de neurologie de l'hôpital cantonal d'Aarau.Méthode : Au total, 66 patients souffrant de SEP ont été traités par la mi¬toxantrone dans la période 07/2000-06/2007. 48 d'entre eux avaient reçu préa¬lablement une autre substance modifiant l'évolution de la maladie (« prétrai¬tement » : interféron bêta-la/b, glatirameracétate, azathioprine). Dans cette étude rétrospective, nous avons comparé l'effet de la mitoxantrone par rapport au prétraitement mentionné ci-dessus. Les paramètres appliqués concernaient l'évolution de l'expanded disability status scale (EDSS) et le nombre annuel de poussées pendant la durée du traitement. Une influence du type de SEP, de l'âge au début du traitement par la mitoxantrone, du sexe, de la durée de la théra¬pie et de la maladie ainsi que de la dose cumulative de la mitoxantrone a été recherchée. Nous avons également discuté des éventuels effets indésirables surve¬nus. Nous n'avons pas différencié les substances du prétraitement, étant donné qu'elles avaient été appliquées dans des combinaisons multiples. L'évaluation sta¬tistique a été effectuée en respectant les indications du test de Mann-Whitney ainsi que du Wilcoxon signed-rank test.Résultats : En moyenne, l'EDSS s'est stabilisée (-0,05/année chez tous les 66 patients) tandis que la maladie avait progressé de 0,32/année sous le pré¬traitement (la différence est significative avec p=0,0004 au Wilcoxon signed- rank test bilatéral). Sous le prétraitement, les patients avaient subi en moyenne 1,72 poussées par année, sous la mitoxantrone 0,26 (différence significative avec p<0,0001). La thérapie a dû être arrêtée à cause d'effets indésirables chez quatre patients sous la mitoxantrone (deux avec une granulocytopénie, deux avec une diminution de la fraction d'éjection cardiaque).Discussion : La mitoxantrone s'est avéré une substance particulièrement ef¬ficace même dans les situations dans lesquelles le décours de la maladie n'a pas pu être influencé par d'autres médicaments. Ses effets indésirables doivent être pondérés par rapport à la progression de la maladie et aux effets indési¬rables des autres substances. Les schémas d'application varient beaucoup dans la littérature et doivent être mieux définis.Zusammenfassung :Einleitung: Mitoxantron ist ein zytostatisches Anthracenedion mit immunsup- pressiven und -modulatorischen Eigenschaften, das unter anderem bei schwe¬ren Verläufen der Multiplen Sklerose eingesetzt wird. Bisher befassten sich nur wenige randomisierte und plazebokontrollierte Studien mit Wirksamkeit und Tolerabilität des Medikamentes.Methoden: 66 MS-Patienten der neurologischen Klinik des Kantonsspitals Aar- au wurden zwischen Juli 2000 und Juni 2007 mit Mitoxantron behandelt. 48 davon erhielten zuvor eine MS-spezifische Behandlung mit Interferon ß-1 a oder b, Glatirameracetat oder Azathioprin. Anhand der Veränderung der Expanded Disability Status Scale (EDSS) und der jährlichen Schubrate und mit Hilfe von MRI-Aufnahmen zeichneten wir retrospektiv die Wirksamkeit der Behandlung nach und stellten sie in Beziehung zu einer eventuell erfolgten Vorbehandlung. Des weiteren wurde die Effektivität in Verhältnis zu den Faktoren Verlaufsform, Alter bei Behandlungsbeginn, Behandlungszeit sowie weiteren Parametern ge¬bracht. Wir verglichen die Wirkung von Mitoxantron bei den noch laufenden Behandlungen mit der bei den bereits abgeschlossenen und wir diskutierten die Veränderung von MRI-Aufnahmen des ZNS unter der Therapie mit Mitoxan¬tron. Nebenwirkungen wurden erwähnt.Resultate: Im Durchschnitt wurde der EDSS-Wert stabilisiert (-0, 05/Jahr bei allen 66 Patienten), während die Krankheit unter der verlaufsmodifizierenden Vorbehandlung um durchschnittlich 0,32/Jahr fortschritt (Unterschied signifi¬kant mit p=0,0004 im zweiseitigen Wilcoxon signed-rank test). Die Schubrate betrug 0,26 unter Mitoxantron gegenüber 1,72/Jahr unter Vorbehandlung (Un¬terschied signifikant mit p<0,0001). Bei vier Patienten musste die Therapie auf¬grund von Nebenwirkungen abgebrochen werden (zweimal Granulozytopenie, zweimal verminderte kardiale Auswurffraktion).Diskussion: Mitoxantron ist offensichtlich selbst dann eine äusserst effektive verlaufsmodifizierende Substanz, wenn die Krankheit durch andere Medikamen¬te nicht zu beeinflussen ist. Die Risiken des Medikamentes müssen gegen das Krankheitsfortschreiten und die Nachteile anderer verlaufsmodifizierender Sub¬stanzen abgewogen werden. Die Anwendungsalgorithmen für Mitoxantron vari¬ieren in der Literatur sehr und müssen besser definiert werden.