Interferon Beta-1a In Patients Research Articles

Review of the clinical evidence for interferon β 1a (Rebif®) in the treatment of multiple sclerosis

Interferon (INF) beta 1a 22 or 44 mug (Rebif((R))) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF beta 1a 22 or 44 mug s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs beta in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif((R)). Additional evidence indicated a beneficial effect of INF beta 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF beta 1a 22 or 44 mug s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable.

Health‐related quality of life in multiple sclerosis: effects of natalizumab

To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300 mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-beta-1a) plus natalizumab 300 mg (n = 589), or IFN-beta-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab.

Évaluation d'un programme d'éducation à l'auto-injection chez des patients atteints de sclérose en plaques rémittente débutant un traitement par interféron bêta-1a intramusculaire: Étude descriptive, multicentrique, non randomisée

In France, self-administration is less common for intramuscular (IM) than parenteral injections, because of the widespread availability of home visits by nurses, who can give these IM injections. An easy, personalized training program was set up to help French patients who wanted to be self-sufficient regarding their injections.This noncomparative, open-label, multicenter study enrolled patients aged 18-75 years, diagnosed with relapsing-remitting multiple sclerosis (MS), with at least 2 relapses during the previous 3 years, no evidence of progression between relapses, and treated with IM interferon beta-1a. The main objective was to assess the proportion of patients able, according to their treating neurologist, to perform the IM injections on their own at the end of an 8-week training program led by nurses.The study included 440 patients (74% women, mean age=38.7+/-9.8 years) at 98 MS centers. At the end of the study, 87% were assessed as "able" to self-inject, and 86.6% of this group could do so by the second injection. Patients' satisfaction regarding the training program was high (89.4+/-13.4 mm at week 4. 89.5+/-12.1 mm at week 8 on a visual analog scale rated from 0 to 100 mm), as was their satisfaction regarding the injection (82.7+/-21.2 mm at week 4 and 84.2+/-20.0 mm at week 8). The correlation between the nurses' and neurologists' evaluations of the patients' ability to self-inject was high, exceeding>90%.This large-scale study demonstrated the feasibility of IM self-injection of interferon beta-1a in patients who want to administer their own injections.

Methylprednisolone, Mycophenolate Mofetil, or Cyclophosphamide as Combination Therapy With Interferon Beta-1a in Patients With Multiple Sclerosis: Retrospective Study

Currently approved disease-modifying therapies for multiple sclerosis (MS) are only partially effective. This study evaluated the efficacy and safety of combination therapy with intramuscular (IM) interferon beta (IFNβ)-1a (Avonex) in patients with disease that progressed despite treatment. A retrospective chart review of all patients from the MS Center of Atlanta, Georgia, was performed (N ≈1300). Eligible patients had a diagnosis of relapsing MS, were treated with IM IFNβ-1a for ≥12 months before initiation of combination therapy, and were on combination therapy for active disease. In addition, patient records must have contained data on relapses, Expanded Disability Status Scale (EDSS) scores, magnetic resonance imaging (MRI) scans, laboratory values, and adverse events. Patients were identified who had been treated with the following in addition to IM IFNβ-1a: pulse corticosteroids only (n = 25), pulse corticosteroids plus mycophenolate mofetil (n = 8), and pulse corticosteroids plus cyclophosphamide (n = 13). The annualized relapse rate was significantly reduced by all three treatments compared with monotherapy (all P ≤.01). For all three groups, no significant improvement was observed with combination therapy compared with monotherapy on evaluations of stable EDSS scores and MRI scans. Three serious adverse events were noted, with two considered related to study medication: one with mycophenolate mofetil (abnormal liver function test results resolved with discontinuation of drug) and one with cyclophosphamide (white blood cell count decrease resolved by withholding one dose). These data suggest that combination therapy is a viable option for the treatment of active MS.

Pregnancy outcomes during treatment with interferon beta-1a in patients with multiple sclerosis

Although patients with multiple sclerosis (MS) are advised to stop interferon (IFN) beta-1a therapy before becoming pregnant, some patients become pregnant while on treatment. We examined individual patient data from eight clinical trials with IFNbeta-1a. Of 3,361 women in the studies, 69 pregnancies were reported, of which 41 were patients receiving (or who had stopped receiving within 2 weeks prior to conception) IFNbeta-1a (in utero exposure group), 22 were patients who discontinued IFNbeta-1a treatment more than 2 weeks before conception (previous exposure group), and six were patients receiving placebo. The 41 in utero exposure pregnancies resulted in 20 healthy full-term infants, one healthy premature infant, nine induced abortions, eight spontaneous abortions, one fetal death, and one congenital anomaly (hydrocephalus). One patient was lost to follow-up. The 22 previous exposure pregnancies resulted in 20 full-term healthy infants, one healthy premature infant, and one birth-related congenital anomaly (Erb palsy). The majority (21/31) of pregnancies that had the potential to go to full term produced healthy infants. The rate of spontaneous abortion was higher, but not significantly so, in the in utero exposure group compared to general population estimates. Until more exposure data become available, patients remain advised to stop IFNbeta therapy before becoming pregnant.

Injection-Site Pain in Patients With Multiple Sclerosis: Interferon Beta-1b Versus Interferon Beta-1a

A single-center, open-label, comparative pilot study was undertaken to assess injection-site pain associated with 10 consecutive subcutaneous injections of interferon beta-1b 250 μg every other day or interferon beta-1a 44 μg three times weekly in patients with multiple sclerosis (MS). Injection-site pain was assessed by the patients with a 10-cm visual analog scale (VAS) score. Recordings were made before each injection and at 10 minutes, 1 hour, and 24 hours postinjection. Ten patients were enrolled in each treatment group. The proportion of injections associated with no pain or no increase in pain at 1 hour postinjection was higher with interferon beta-1b (47%) than with interferon beta-1a (27%). Mean pain severity was also less intense with interferon beta-1b than with interferon beta-1a. Differences in VAS scores were seen immediately after injection (1.04 versus 3.14 cm, respectively) and at 10 minutes (0.40 versus 1.70 cm) and 1 hour (0.33 versus 1.50 cm) postinjection. These findings indicate that subcutaneous injection with interferon beta-1b is associated with a lower incidence and severity of pain than subcutaneous injection with interferon beta-1a in patients with MS. The results should assist MS nurses and physicians in supporting patients to make an informed choice regarding potential side effects when deciding on an appropriate disease-modifying therapy.

0564 Long-term sustained efficacy and safety of subcutaneous (Sc) interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS): The PRISMS 7–8 year results

0564 Long-term sustained efficacy and safety of subcutaneous (Sc) interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS): The PRISMS 7–8 year results