Pregnancy and immunomodulatory therapy in multiple sclerosis patients

Pregnancy and family planning issues are prominent concerns in the medical care of multiple sclerosis patients, since the disease onset often coincides with a period of life that is decisive in this regard. Multiple sclerosis is a chronic disorder with an unpredictable course and is widely treated with long-term immunomodulatory agents, raising questions regarding the complications and effects of these therapies on pregnancy. This paper gives an overview of the relevant literature and provides a basis for individual counselling of this group of multiple sclerosis patients.     

Other immunomodulatory therapies in multiple sclerosis

This short review concentrates on immunomodulatory disease-modifying approaches that are under development for the treatment of multiple sclerosis based on present concepts of the immunopathogenesis of the disease that especially involve T-cells and macrophages as being prominently involved in inducing tissue destruction and on the advances that have been made in recent years by studying other treatment interventions that have been applied and that have been shown to be either successful (interferon beta, copolymer-1) or unsuccessful (many others).     

Combination therapy for multiple sclerosis

To improve the partial benefit of approved monotherapies in multiple sclerosis (MS), over 25 combined therapies have been tested in recent years, either as fixed-dose or sequential combination regimes. The main therapeutic targets for combination therapy in MS are the same as for monotherapy: the immune-mediated inflammatory cascade, oxidative toxicity and excitotoxicity. There are numerous reasons to consider combination therapy in MS, including to improve the benefit and/or tolerance in patients responding to approved treatments, stop frequent disabling relapses and/or rapid progression in patients who do not respond to approved therapies, and maintain the benefit of immunosuppressive treatments. Preliminary clinical trials suggest that combination therapy in MS does not increase the side-effects of approved monotherapy; its efficacy over monotherapy should therefore be tested. Statistically robust trials would need to involve many patients for each combination, so the first step in determining the efficacy of combination therapy should be to perform safety studies, followed by proof-of-concept efficacy studies.     

The effect of immunomodulatory treatment on multiple sclerosis fatigue

OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.     

Recent developments in drug therapy for multiple sclerosis.

Symptomatic treatment of multiple sclerosis (MS) includes a diverse range of drugs intended to relieve the specific symptoms with which a patient may present at a particular point in the progression of the disease. These drugs, not specifically designed for the treatment of MS, may include antispastic agents (e.g. baclofen), drugs to reduce tremor (e.g. clonazepam), anticholinergics (e.g. oxybutynin) which relieve urinary symptoms, anti-epileptics (e.g. carbamazepine) to control neuralgia, stimulants to reduce fatigue (e.g. amantadine), and antidepressants (e.g. fluoxetine) to treat depression. The treatment of acute relapses or exacerbations is dominated by corticosteroids such as methylprednisolone. The most active area of current investigation is the development of drugs which will inhibit the progression of the disease process itself, and in this category the beta- and alpha-interferons are the most effective drugs currently available, although many new treatments are currently in trials, including immunoglobulin, copolymer-1. bovine myelin, T-cell receptor (TCR) peptide vaccines, platelet activating factor (PAF) antagonists, matrix metallo-proteinase inhibitors, campath-1, and insulin-like growth factor (IGF).     

Immunologic therapy for relapsing-remitting multiple sclerosis

The treatment of relapsing-remitting multiple sclerosis (RRMS), the most common form of multiple sclerosis, has been revolutionized in recent years. In addition to effective treatment of acute relapses, therapies are now available to prevent relapses, reduce the burden of disease as seen on magnetic resonance imaging, and possibly even slow the course of disease. There are now several agents either approved, awaiting approval, or in various stages of development in many countries. Evidence suggests that early intervention with these agents will yield the best results in the long run. The current approach to treatment of RRMS is the focus of this discussion.     

Early immunomodulatory treatment of multiple sclerosis: pros and cons

Early immunomodulatory treatment of multiple sclerosis has raised great hopes, especially among MS patients and their families. However, there are considerable differences of opinion among medical professionals, particularly as regards the economic aspect of the therapy (often undertaken before any definite diagnosis is made). The findings documenting early irreversible axonal lesions and brain atrophy in MS, as well as results of clinical studies suggest that early immunomodulatory treatment is the method of choice, even if critical arguments are taken into account.     

Amantadine therapy for fatigue in multiple sclerosis

We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5% unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects.     

Early intervention with immunomodulatory agents in the treatment of multiple sclerosis

Multiple sclerosis (MS) is a lifelong neurologic disease leading to moderate or severe disability in the majority of affected patients. Studies of the natural history of MS suggest that 90% of patients with relapsing-remitting MS eventually develop secondary progressive (SP) disease. Magnetic resonance imaging (MRI) studies have consistently shown a high frequency of new T2 lesions and new gadolinium enhancing lesions even in the absence of clinical relapse. Lesion burden on T2 MRI increases by 5% to 10% per year and both axonal transection and cerebral atrophy are present at the earliest stages of RR MS. A wealth of evidence suggests that MS is a disease process that is continuously active, and that irreversible damage occurs early in the disease. Despite knowledge of the natural history and the availability of treatments that reduce relapse rates, decrease the accumulation of disability, and decrease surrogate measures of disease activity, only 60% of eligible patients have been treated with immunomodulating agents. This paper reviews the available evidence suggesting that immunomodulatory therapy modifies the natural history of MS and presents an argument for early intervention in the treatment of MS.