Judith Haas

Mycophenolate-mofetil in the treatment of refractory multiple sclerosis.

Sirs: Multiple sclerosis (MS) is thought to be an autoimmune disease stimulated by activated lymphocytes, and the entry of T and B cells into the central nervous system [1]. Despite the use of a variety of immunomodulatory and immunosuppressive agents including interferon beta, glatiramer acetate, intravenous immunoglobulins, azathioprine and escalating chemotherapy with mitoxantrone and cyclophosphamide, MS remains progressive in a large number of patients and there is an ongoing need for further rescue therapy [2, 3]. Mycophenolate-mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase, which is necessary for de novo purine biosynthesis in lymphocytes. The drug is being successfully and increasingly used for prevention of organ transplant rejection [4]. Beneficial effects in the treatment of autoimmune diseases have been shown in Crohn’s disease [5]. The inhibition of lymphocytes by the drug may therefore result in improvement in patients with refractory MS. In this open surveillance trial, we treated seven patients with chronic progressive or relapsing MS (table). The patients were informed about the drug and its attendant risks, and all gave informed consent before initiation of treatment. Entry criteria in this trial included the diagnosis of MS, disease-progression in terms of EDSS despite established treatment (table), and no other diseases such as infections or liver or kidney disorders. All patients received the usual dose employed in the treatment of transplanted patients (2 g per day). The administration of MMF led to improvement or stopped progression in five cases (table). Three of the five patients emphasized improved movement, although EDSS did not change. One of the five patients (no. 7) had to reduce the dose from 2 to 1.5 gr per day because of frequent infections, one (no. 2) discontinued the treatment owing to uncontrolled nausea. Two patients without beneficial effects stopped the drug through nausea and/or non-response (nos. 3 and 5). MRI findings before and at least 6 months after treatment start were available in two patients (no. 1 and 7) and showed fewer lesions and no change, respectively. The four patients, who still receive MMF, are feeling well without progression and would like to continue this therapy. In all seven treated patients there was no deterioration concerning EDSS. Although the beneficial effects in five patients demonstrate that MMF may be of value in the treatment of MS, this open-label study does not allow a final conclusion. The question of whether more responsive patients would be found in an unselected group requires further study. LETTER TO THE EDITORS

Multiple Sclerosis Registry in Germany: Results of the Extension Phase 2005/2006

INTRODUCTION In 2001, a nationwide multiple sclerosis (MS) registry was initiated in Germany under the auspices of the German MS Society, (DMSG Bundesverband e.V.). The project aimed at collecting epidemiological data and information on health care provision for MS patients in Germany. METHODS After a 2-year pilot phase, the original entry mask was modified, and new centers were recruited, resulting in the registration of a total of 5821 patients in 2005 and 2006. Following a 2 stage quality control process, standardized data sets for 5445 patients (93.5%) were able to be analyzed. RESULTS Mean duration from onset of disease to diagnosis was 3.5 years. More than 70% of patients received immunomodulatory drugs, whereas symptomatic treatments were less commonly administered. The number of participating centers as of 31 December 2006 was 57 (29 neurological hospitals, 11 rehabilitation units, 13 specialized practitioners, and 4 regional MS centers). DISCUSSION The MS registry provides valuable data on patterns of care for MS patients in Germany, and may help to improve service provision and overall quality of life for these patients.

Current issues in immunomodulatory treatment of multiple sclerosis--a practical approach.

Immunomodulatory treatment of multiple sclerosis (MS) has been widely available for the last decade; however, treatment recommendations are not uniform. Many situations and questions arising in everyday practice are not reflected in clinical trials and can not be answered on the basis of evidence based research. The purpose of this review is to critically discuss such situations and to suggest some answers applicable to daily patient care. In particular, the following aspects relevant for the immunomodulatory treatment of MS are discussed: – Implication of diagnostic criteria for early immunomodulatory treatment – Identification of non-responders to treatment – Escalation and deescalation of immunomodulatory treatment – MRI for treatment follow-up – Pregnancy and immunomodulatory treatment

IVIG trials in MS. Is albumin a placebo

JO N 2 89 3 unexpected results in RRMS has not been presented so far. We therefore critically reviewed all published RDBPC trials of IVIG in MS. Fifteen studies were identified. Eight studies used albumin as a placebo (Table 1). These trials did not show a difference between verum and placebo, except for the PP/SP study [3] in which the PP subgroup (n = 18) showed some benefit of active treatment. In two studies the primary end-point was MRI. One study was positive ([4]; Table 1). Six of seven RDBPC studies with saline, dextrose or vehicle (SDV) as the placebo arm showed a positive effect of IVIG (Table 2). Four studies in RRMS were positive, three with clinical endpoints [5–7] and one with MRI endpoints [8]. One study in clinically isolated syndrome (CIS) patients showed significant postponement of conversion to definite MS [9]. One study in acute optic neuritis, with both arms receiving IFB, did not show an IVIG effect [17]. The remaining single cross-over study in stable motor deficit received placebo for 5 days, followed by 6 weeks observation, then IVIG for 5 days and 6 weeks observation. The primary endpoint, central motor conduction time, did not show a difference. The Scripps Neurological Rating scale showed a significant improvement after IVIG [10]. Eight RDBPC trials comprising around 900 patients did not show a difference between placebo and verum (Table 1). Seven RDBPC trials with a total of 315 patients with SDV as placebo were clearly positive for IVIG (Table 2). The chance of a positive outcome in RDBPC IVIG trials is far higher in SDV than in albumin-controlled trials. The trials reviewed here are quite different in design, patient number, endpoints and exposure to treatment. Equal weight of evidence cannot be given to each trial. Otto Hommes Judith Haas Per Soelberg-Sorenson Mieke Friedrichs

MS in Deutschland: Symptome und Behandlungsdefizite

Über die Situation der Menschen mit Multipler Sklerose war lange wenig bekannt. Verlässliche Daten zur Häufigkeit der Erkrankung und ihren Unterformen gab es nicht. Auch Versorgungsaspekte, wie verlaufsmodifizierende beziehungsweise medikamentöse und nicht medikamentöse symptomatische Therapien der Erkrankung waren nur für einzelne Einrichtungen und ihre Patienten bekannt. Das MS-Register wurde 2001 initiiert, um standardisierte Daten zu diesen Punkten, aber auch über den Einfluss der Erkrankung auf die Berufstätigkeit oder Arbeitsunfähigkeit der Betroffenen zu erhalten. Der nachfolgende Artikel gibt einen Einblick in die aktuelle Versorgungssituation MS-Kranker und gestattet erstmals einen historischen Vergleich.