Hi- and, can anyone post or send me the ECTRIMS abstracts on IVIg?

[Lazarus]

My system is quite primitive and I have tried but can not access anything. There were 2 papers presented on the first day--wednesday. (I think)

I'm off to my 8 hours of infusion! Thanks to anyone who posts any abstracts.
Linda Lazarus

[cricket52]

Hi Lazarus:

There is a session on Wednesday entitled "IVIG in relapsing-remitting multiple sclerosis - A solution for the predicament", however, there are no abstracts posted in any of the sessions underneath it.

I scanned the other days, didn't find anything. Could have overlooked something though. Sorry.

[xo++]

Hi Linda,

As Cricket mentioned a few of the IVIg abstracts have yet to be posted, but several were available.

The different commercial preparations seem to differ in effectiveness, with the suggestion that preparations of IVIg enriched with IgM are more effective.

Although the trials reported in these abstracts were open label (i.e. neither patient nor examiner were blinded), both trials reported stable or improved disability scores in the patient groups receiving IVIg.

Mark

Long-term therapy with IV-immunoglobulins in multiple sclerosis. Evaluation of a prospective documentation of 668 patients

E. Maida (Vienna, A)

Multiple sclerosis (MS) can neither be cured nor stopped completely, but by immunomodulating therapies the occurrence of severe incapacities can be delayed in the majority of patients, especially, when introducing the treatment during the first years after the onset of the disease. The immunomodulating properties of i.v.-immunoglobulins (ivIG) refer to both T-helper- and B-cells and and they serve for treatment in several autoimmune diseases.

Trials in MS already have been performed since more than 20 years. Although from many studies encouraging results had been obtained, the use of i.v.-immunoglobulins in MS is still controversial.

The actual presentation is based on datas obtained from an open prospective documentation, which started in 1993, of relapse rates, EDSS-scores and MRI observations of relapsing-remitting MS-patients, who had received 200mg/kg body weight of 7S-immunoglobulines every 21-28 days for at least 2 years (earlier withdrawals included). 668 patients were evaluated.

In 10% therapy was stopped earlier (mostly because of problems with veins and allergy). Before starting ivIG the mean duration of MS was 7,6 years, the mean relapse rate was 2,8 per 24 or less months, the mean EDSS was 3,5. The mean duration of ivIG-treatment until the actual evaluation was 35 months.

Results: 51 % of the patients remained relapse-free, a mean reduction of relapse rates of –2,2 was observed, the mean EDSS-score showed a reduction of –0,3. No further progression and/or Gd+ activity was seen in the majoroty of MRI scans of both brain and cervical spine. An additional evaluation of subgroups of the patients showed a positive correlation of ivIG effects on relapse rates, EDSS-scores and stability in MRI respectively and the duration of MS at the time of starting the treatment.

Conclusion: The evaluation of a large number of patients points out the high effectiveness on reducing the progression of MS both clinically and in MRI by ivIG-therapy. Furthermore it was excellently tolerated. The rather low dosage, which was used for the present documentation showed similar good effects like studies with higher dosages of ivIG, beta-interferons and glatiramer-acetate, but was more economic. The acutal datas revealed the high therapeutic value of ivIG in relapsing-remitting MS.
__________________

Retrospective analysis of immunoglobulin therapy in a group of Portuguese multiple sclerosis patients

J. Guimarães, M.E. Rio, J. Reis, M.J. Sá (Porto, P)

Introduction: High-dose intravenous immunoglobulins (IVIg) became a successful new treatment regimen in neurological autoimmune diseases. As regards Multiple Sclerosis (MS), the clinical trials of IVIg showed that IVIg may have beneficial effects in different disease courses. Retrospective observational studies, like the present one, might further support these available results.

Purpose: In this retrospective study we aimed to evaluate the relapse rate and clinical disability of MS patients treated with IVIg, who fulfilled inclusion criteria for a second line immunomodulatory therapy.

Patients and Methods: A total of 22 MS patients (relapsing/remitting, 17; progressive, 5; mean age 40+-10years) were treated monthly with 0.2 g/kg body weight of IVIg for 24 months. The sample included 4 patients who had stopped a prior immunomoduladory drug (IMD) and started IVIg in monotherapy, and 18 patients in add-on therapy regimen with other IMD (Betaferon: 10 patients; Avonex: 2 patients; Rebif: 4 patients; Copaxone: 2 patients) due to treatment failure.

The outcome measures were: the effect on clinical disability measured by the change in Kurtzke`s expanded disability status scale (EDSS) score, as the proportion of patients with improved, stable or worse clinical disability (>=1.0 grade on EDSS score); Multiple Sclerosis Severity Score (MSSS, the relationship between EDSS and duration) and mean annual relapse rate (ARR) during 2 years of IVIg treatment, compared to MSSS and ARR values 2 years before IVIg treatment, irrespective of the previous therapy.

Results: The mean ARR decreased from 2.3 ± 2.1 during the 2 years prior to the start of IVIg to 1.1± 1.2 within the first two years after IVIg therapy. EDSS values remained stable throughout the observation period (mean EDSS before and after IVIg: 3.5); however, the severity improved in 17 patients (mean MSSS before IVIg: 5.1± 2.8; mean MSSS after IVIg: 4.6±3.1).

Discussion: Our results are similar to the results of previous studies with IVIG in monotherapy that report beneficial effects of IVIG on relapse rate and in disease progression; in addition, in our population the clinical improvement was observed in MS severity evaluated by MSSS. In conclusion, IVIg as add-on therapy may be a valuable alternative treatment that can be considered in patients whose benefit of first line MS medications alone is modest.

_______________

Concentrations of cytokines and adhesion molecules in commercial immunoglobulin preparations: relevance for the treatment effect in MS patients

K. Retzlaff, C. Roth-Langer, R. Reuß, S. Vogel, C.V. Burger, M. Kaps, P. Oschmann (Giessen, D)

Introduction: Many studies have shown that intravenous immunoglobulin preparations (IVIG) are effective in the treatment of relapsing remitting multiple sclerosis (RRMS). Up to know the definite mode of action is still unknown. A wide spectrum of action is assumed, among other things the blockade of T-cell-receptors and the modulation of pro- and anti-inflammatory cytokines.

Commercial IVIG preparations are made from human blood. We investigated the existence of other immunological parameters (cytokines, adhesion molecules) in these preparations and a possible influence on the treatment effect of IVIG in MS patients.

Materials and Methods: At a single point in time we analysed IVIG preparations from seven different manufacturers, some of them from different charges. We measured the cytokine (TNF-b, sIL-4R, TNF-R I+II) and adhesion molecule (sICAM-1, sVCAM-1) concentration using commercialised ELISA-systems.

Additionally, two patient groups were treated with two different IVIG preparations (IVIG A: n=6; IVIG B: n=4) and were observed over a 12 months period. Blood sampling was done every 3 months for determining the serum concentrations of the cytokines and adhesion molecules.

Results: Comparing the seven commercial IVIG preparations varying concentrations of all parameters were shown, particularly remarkable for TNF-RI (values from 836,31 to 1536,76 pg/ml) and TNF-RII (values from 986,1 to 9240,36 pg/ml). Even in different charges of one IVIG preparation fluctuations of the concentrations could be proven (e.g. IVIG B; sIL-4R : range from 63,16 to 139,42 pg/ml).

Under treatment over 12 months we could prove an induction of the cytokines TNF-b and TNF-R I+II. A difference in the extent of the induction were shown with the two different IgG preparations (e.g. IVIG A; TNF-b (mean): range from 399,14 to 1100,18 pg/ml; IVIG B : range from 156,33 to 404,13 pg/ml).

Conclusions: Our results show varying concentrations of cytokines and adhesion molecules in different IVIG preparations. Under treatment over 12 months the different induction of some cytokines might be one mode of action of IVIG in MS-patients. The different extent of the induction could be due to the different influence of the cytokine concentration in the two IVIG preparations

[xo++]

And here's one more that I had to put into a different post because of the 10,000 character limit of the forum....

Mark

Predictors of intravenous immunoglobulins effectiveness in multiple sclerosis

G.N. Bisaga (St.Petersburg, RUS)

Introduction: Among immunomodulators for multiple sclerosis (MS) treatment intravenous immunoglobulins (IVIgs) are marked out not only low frequency of side effects and ability to reinforce remyelination in CNS, but also high clinical efficiency, which depends on a number of factors, which we had analized.

Methods: 45 clinically defined MS patients (F/M=29/16, aged 4 - 54 (35.4±11.2) years, EDSS 1.5 – 9.5 (4.4±2.2)) are surveyed. RRMS – 26 pts, SPMS -13, PPMS - 3 and RPMS - 3. The duration of IVIgs treatment was 3 - 72 (11.1+/-10.8) months. The patients received IVIg enriched IgM (Pentaglobin “Biotest”; n=24) and IVIgs, on 99% consisting from IgG (Intraglobin “Biotest”; n=21).

Doses: 0.4 g/kg within 3 days and then monthly 0.15-0.20 g/kg within 3-72 months. A positive clinical effect was fixed in case of reduction of relapse number at least on 50 % and/or decrease of EDSS on 0.5 or more points.

Results: Side effects (only slight and intermittent) were seen in 11% of the patients. The positive effect of IVIgs treatment is established in 54% of cases: at RRMS in 74%, SPMS - 39% (p<0.05), PPMS - 0%, RPMS - 0%. Among the patients with RRMS with a positive effect at 59% was revealed strong positive effect, at 41% - moderate; among the patients with SPMS only moderate positive effect (100%) was revealed.

The relapse rate before treatment was 1.4±1.2 per year, during treatment – 0.64±1.0, during a half a year after treatment – 0.65±0.95. Average reduction of EDSS during IVIgs treatment was 0.41±0.40. Higher clinical efficiency of IVIg enriched IgM is established in comparison with containing only IgG: 60% and 48% accordingly.

The efficiency of IVIgs did not depend on age of the patients and duration of disease. The weak positive correlations were revealed between efficiency of treatment and relapse rate before treatment (r=0.30; p<0.05), moderate - between effect from treatment and its duration (r=0.53; p<0.01) and weak negative correlations established between result from treatment and initial EDSS (r =-0.31; p<0.05).

[Lazarus]

The paper about different commercial preparations that you posted, Mark, was exactly the info I am interested in~~~~~Bluesky posted many articles about the subject.

I had become cocky with my wellness and had insisted that I would do infusions once a month. That has lasted 2 months and today my neurologist switched me to every 3 weeks. But I want to investigate the different preparations. I also want to investigate whether people can handle novantrone and IVIg.

Again, thanks.
Linda