Ten years of adverse drug reaction reports for the multiple sclerosis immunomodulatory therapies: a Canadian perspective.

Adverse drug reaction (ADR) reporting is essential in the post-marketing surveillance of drugs, detection of serious adverse reactions, and has been the basis for drug withdrawals. The study aimed to examine ADR reporting patterns to the multiple sclerosis (MS) immunomodulatory drugs (IMD) in Canada. All ADRs reported to the Canadian ADR Monitoring Program (CADRMP) from 1965 to March 2006 (n=193 208) were accessed and ADRs in which an IMD for MS (beta-interferon or glatiramer acetate) was the suspected drug extracted (n=888 reports were dated March/96-March/06). Almost half of all IMD ADRs reports (438/888) were sourced through the patient compared to 14.9% (10 649/71 373) of all ADRs reported to CADRMP over the same period. Of IMD ADR reports, 88.7% (788/888) were directed through the manufacturer compared to 57.7% (41197/71373) of all ADRs. Encouragement to others involved in patient care, such as pharmacists, nurses and physicians might enhance reporting of MS ADRs. Despite the limitations of ADR reporting data, previously unpublished case reports in several understudied MS populations were detailed: paediatrics (or= 65 years, n=23) and during pregnancy (n=12). In addition, 46 deaths suspected by the reporter as being related to IMD treatment were detailed as well as three possible drug interactions.

Asthma and multiple sclerosis: an inverse association in a case-control general practice population.

BACKGROUND: Th1/Th2 imbalance is hypothesized to up-regulate some diseases and down-regulate others. Compared to controls, multiple sclerosis (MS) (Th1-mediated) has been linked to a reduced risk of allergy and asthma (Th2-mediated), based on patient questionnaire studies and a review of asthma medication. AIM: To investigate whether MS is associated with a reduced risk of Th2-associated diseases and an increased risk of Th1-associated diseases. DESIGN: Retrospective matched case-control study. METHODS: Three hundred and twenty MS patients and controls matched for age, gender, location and smoking were selected from the Welsh General Practice Morbidity Database from 1995-99. Case and control records were assessed for Th1-mediated and Th2-mediated diseases. RESULTS: Overall, 346 MS patients were identified, giving a prevalence of 127 per 100 000. There was an inverse relationship between multiple sclerosis (MS) and asthma (OR 0.33; 95%CI 0.15-0.77). No statistically significant relationships emerged between other Th2-associated (eczema, dermatitis) or any Th1-associated (rheumatoid arthritis, thyroid disorders, inflammatory bowel disease [IBD], type 1 diabetes) diseases and MS, although no patient in either group had treated type 1 diabetes. A trend existed for IBD, with 5/320 of cases affected and no controls; OR infinity; 95%CI 1.30-infinity; p=0.063. DISCUSSION: This inverse association between MS and asthma is compatible with a Th1/Th2 imbalance. Although the Th1/Th2 theory is probably an over-simplification in MS, a shift from Th1 cytokine dominance towards Th2 may provide drug-targeting routes for MS.

Prescribing for multiple sclerosis patients in general practice: a case-control study.

OBJECTIVES: To examine the prescribing patterns for multiple sclerosis (MS) patients resident in Wales by general practitioners (GPs), compared to an age, gender and GP surgery matched control population. METHODS: Anonymised data for 1996 were obtained for all patients from 24 GP practices in the all-Wales General Practice Morbidity Database (GPMD). This covered 220 538 patient years at risk for 1996. Cases were selected as those with a Read code of MS at some point from 1993 to 1996 (therefore had consulted the GP at least once during this time). The controls were age, gender and surgery matched patients randomly selected from the GPMD. RESULTS: A total of 216 cases were identified, giving a prevalence of 97.9 per 105. Cases were prescribed a mean of 15 drugs each in 1996 compared to eight drugs for controls (P < 0.0005). Compared with controls, MS patients were prescribed significantly more laxatives, diuretics, hypnotics and anxiolytics, antidepressants, antiepileptics (mainly carbamazepine), corticosteroids, oxybutynin, vitamin B12 and skeletal muscle relaxants (predominantly baclofen; P < 0.05). Certain 'MS specific' drugs were not frequently prescribed, such as cytotoxic immunosuppressants (two cases), amantadine (one case) and isoniazid (no cases). No case was prescribed medication for erectile dysfunction. Over 80% (44/53) of corticosteroid prescriptions for MS were for oral prednisolone. Over one-third (39%, 9/23) of cases prescribed a corticosteroid received a 'chronic' course. Over one-third (5/14) of courses of selective-serotonin re-uptake inhibitors (SSRI) for cases were identified as subtherapeutic. CONCLUSIONS: MS patients were high users of prescribed medicines, having almost twice as many prescriptions from the GP compared to controls. GP prescribing often reflected available evidence from published controlled trials, hence cytotoxic immunosuppressants, drugs for fatigue and tremor were seldom prescribed, whereas drugs such as oxybutynin and skeletal muscle relaxants were frequently prescribed. However, the increased use of certain drugs compared to controls such as diuretics, vitamin B12, hypnotics and anxiolytics were unsubstantiated in the literature. Furthermore, no published well-controlled clinical trials were found utilizing oral prednisolone or assessing the possible therapeutic benefit of chronic courses of corticosteroids in MS, both of which were prescribed by the GP. The absence of medication for sexual dysfunction (prelicensing of sildenafil), a reportedly common MS problem, was discussed. The relatively high incidence of subtherapeutic courses of SSRIs needs further investigation, given the increased incidence of depression and suicide associated with MS.

Nonprescription medicine use in a multiple sclerosis clinic population.

AIMS: To determine the use of nonprescription medicines in a cohort of multiple sclerosis (MS) patients and to identify a subgroup of patients liable to spend more on nonprescription medicines METHODS: A questionnaire was given to MS patients attending a neurology out-patients clinic during the previous year. Medicines from a General Practitioner (GP), pharmacy and 'other' sources utilized in the last month were determined, along with demographic data. Additional information was obtained from hospital notes. RESULTS: One hundred and seventeen MS patients responded to the questionnaire, giving a response rate of 79% (117/148). Responders differed from nonresponders only in age, with responders being significantly older than nonresponders (P = 0.011). Over one-third of medicines taken in the last month were nonprescription medicines (35%; 219/627). A gamolenic acid containing preparation was the most popular, purchased by 28% of patients. Fifteen percent (17/117) of MS patients had exceeded the recommended daily allowance of a vitamin (frequently vitamins A, D and E), and one exceeded the upper safe level for daily self-supplementation of vitamin A and D. Females spent significantly more than males in the previous month ( pound10. 09 compared with pound5.53, respectively; P = 0.022). Patients who were older, reported worsening MS symptoms in the last year and those who exhibited greater disability were more likely to have been prescribed medicines by a GP (P < 0.0005), although they were not more likely to self-prescribe or take alternative remedies (P > 0. 05). However, those with poorer mobility were significantly less likely to have purchased a pharmacy medicine in the last month (P = 0.033). CONCLUSIONS: MS patients were high users of nonprescription medicines. A typical subgroup of MS patients that spent more on nonprescription medicines could not be identified, aside from females. Furthermore, the strong predictors for increased use of prescription medicines (increasing age, severity of symptoms in the last year and poorer mobility) were not found for nonprescription medicines. Excessive intake of the fat soluble vitamins could lead to hypervitaminosis, the effects of which could exacerbate or mimic MS symptoms. Health professionals should be aware of these issues and counsel the MS patient accordingly, particularly as the majority purchased products from 'other' sources where typically there is no health-professional available to give advice. The limited use of pharmacy medicines by the more disabled patient could indicate a problem with access to the pharmacy, or could reflect the greater use of prescription medicines.

Use of corticosteroids in multiple sclerosis by consultant neurologists in the United Kingdom.

OBJECTIVES: To survey the use of corticosteroids in multiple sclerosis as recommended by United Kingdom consultant neurologists. METHODS: A postal questionnaire covering the use of corticosteroids for acute multiple sclerosis relapse and chronic progressive multiple sclerosis with regard to frequency of use, type of corticosteroid, and dosage regime was sent to all members of the Association of British Neurologists with a United Kingdom address. RESULTS: Two hundred and twelve United Kingdom consultant neurologists replied to the survey (74% response rate). Eighty six per cent indicated that they prescribed corticosteroids in more than one quarter of acute multiple sclerosis relapses seen. Intravenous methylprednisolone was recommended at some time by 99% of consultant neurologists, the most popular regime being 1g daily for 3 days (74%; 154/ 208). Over one half (53%; 109/206) never recommended a subsequent tapering course of oral corticosteroids; of those that did, 25% (24/96) recommended a tapering course lasting more than 1 month. Eighty eight per cent (1811206) of prescribers of intravenous methylprednisolone were able to offer the course as a day case on the ward; 7% (151206) at an outpatient clinic; and 5% (111206) at home. Almost three quarters of neurologists recommended oral corticosteroids for some acute relapses, although the most popular response was for occasional use only (48%; 1011212). Forty five per cent (961211) at least occasionally recommended steroids for patients with chronic multiple sclerosis not experiencing an acute relapse. CONCLUSIONS: Although the vast majority of consultant neurologists would prescribe intravenous methylprednisolone for acute multiple sclerosis relapse at some time, the use of corticosteroids for multiple sclerosis was otherwise variable. There seemed to be little consensus about the use of oral steroids in acute relapse, the prescribing of a tapering course of oral steroids after intravenous methylprednisolone, or the utility of steroids in chronic multiple sclerosis. Variability of prescribing recommendations probably reflects a lack of clear evidence in the face of a wide range of clinical situations, variable access, and timing of access to neurologists in the acute phase of relapse and pressure on neurologists to treat in an otherwise "hopeless" situation. Large multicentred trials are needed to consider these issues.