Intramuscular Interferon Beta Research Articles

Analysis of Pregnancy Outcomes Following Exposure to Intramuscular Interferon Beta-1a: The AVONEX® Pregnancy Exposure Registry.

There is a lack of well-controlled US studies of intramuscular (IM) interferon beta (IFNβ)-1a use in pregnant women with multiple sclerosis; however, in the European Medicines Agency region, IFNβ formulations may be considered during pregnancy if clinically needed based on data from European Union cohort registries. The AVONEX Pregnancy Exposure Registry was established to prospectively study the effects of IM IFNβ-1a on the risk of birth defects and spontaneous pregnancy loss in a US population. Pregnant women with multiple sclerosis exposed to IM IFNβ-1a within ~ 1 week of conception or during the first trimester were included. Participants were followed until there was a pregnancy outcome, live-born infants were followed until age 8-12 weeks. Data were collected on IM IFNβ-1a exposure, demographics, patient characteristics, medical history, and pregnancy outcomes, including live births (with or without birth defect), spontaneous abortions/miscarriages and fetal death/stillbirth, elective abortions (with and without birth defect), and ectopic pregnancies. A population-based birth defect surveillance program, the Metropolitan Atlanta Congenital Defects Program (MACDP), served as the primary external control group for evaluating the risk of birth defects. Three-hundred and two patients with a median (range) age of 31.0 (16-48) years and a median (range) gestational age at the time of enrollment of 10.1 (4-39) weeks were evaluable. Most patients (n = 278/302; 92%) reported IM IFNβ-1a exposure in the week before conception and most (n = 293/302; 97%) discontinued treatment before the end of the first trimester. Of 306 pregnancy outcomes, there were 272 live births, 28 spontaneous abortions of 266 pregnancies enrolled before 22 weeks' gestation (rate 10.5%; 95% confidence interval 7.2-15.0), five elective abortions, and one stillbirth. There were 17 adjudicator-confirmed major birth defects of 272 live births (rate 6.3%; 95% confidence interval 3.8-10.0); the pattern of birth defects observed was not suggestive of a relationship to prenatal IM IFNβ-1a exposure. This large US registry study suggests IM IFNβ-1a exposure during early pregnancy was not clinically associated with adverse pregnancy outcomes in women with multiple sclerosis. These findings help inform clinicians and patients in weighing the risks and benefits of IM IFNβ-1a use during pregnancy. ClinicalTrials.gov: NCT00168714, 15 September, 2005.

Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: A 16-year non-concurrent cohort study.

Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM βINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

Tolerability, treatment satisfaction and quality of life outcomes in stable multiple sclerosis patients switched from injectable therapies to auto injected intramuscular interferon beta 1a: The SFERA study

BackgroundInterferon beta (IFNB) and Glatiramer acetate, long-term first line disease modifying treatments (DMTs) for multiple sclerosis (MS), have different injection frequencies crucial for injection site related side effects. We aimed at investigating whether switching to intramuscular IFNB-1a injected once/week with the Avonex®Pen™ device improves treatment tolerability and quality of life in stable MS patients. MethodsClinically stable MS patients, whom their treating neurologist switched from high frequency injectable DMTs to weekly intramuscular IFNB-1a because of bothersome injection site reactions, were included. Injection site and systemic tolerability were measured by a composite 100 mm visual analogue scale at screening, months 4 and 12. Treatment satisfaction, quality of life, relapses and EDSS progression were also recorded. The primary endpoint was change in injection site tolerability from screening to Month 4. Descriptive statistics and Wilcoxon paired signed-rank tests were applied. ResultsThe median injection site tolerability and systemic tolerability were significantly improved at months 4 (n = 36) and 12 (n = 33) [change −51.60 (IQR: −60.13, −39.60) mm (p < 0.0001); −26.00 (−54.00, 2.25) mm (p = 0.002)]. Median treatment satisfaction was significantly improved at month 12 [change of 18.00 (2.00, 47.50) mm (p = 0.0003)]. Physical and mental components of the SF-36 did not change significantly, and 30/33 (90.9%) and 33/33 (100%) patients were free from relapses and EDSS progression at month 12. ConclusionsWeekly intramuscular IFNB-1a may represent an alternative treatment option for clinically stable MS patients suffering from intolerable injection-related side effects under treatment with high frequency injectable DMTs.

Does Interferon Beta-1a Impact Pure-Tone Hearing Sensitivity Among Individuals With Multiple Sclerosis?

Previous studies reported that particular types of interferon medications might contribute to hearing loss in some patients. The package insert included in the original Food and Drug Administration application for intramuscular interferon beta-1a (Avonex) stated that some patients in the treatment group reported decreased hearing sensitivity. The purpose of the present investigation was to assess if individuals with multiple sclerosis (MS) taking intramuscular interferon beta-1a have significantly poorer hearing thresholds than those not currently using any disease-modifying therapies. This was a secondary analysis of data collected as part of two larger studies evaluating auditory function in patients with MS. The goal of this analysis was to determine if users of interferon beta-1a do not have significantly worse hearing thresholds than nonusers of disease-modifying therapies, after adjusting for potential confounders. A linear mixed model was fit to the audiometric thresholds of our subjects. This model included interferon beta-1a use, MS disease subtype, gender, test frequency, age, disease duration (number of years), and the Expanded Disability Status Scale score. With all subjects included, there is insufficient evidence to say that intramuscular interferon-beta 1a is not ototoxic (in relation to nonuse of a disease-modifying therapy) at all frequencies tested except 3000 and 6000 Hz. After removing two influential subjects, the results indicated that there is statistical support for no ototoxic effect of intramuscular interferon beta-1a at test frequencies from 250 to 6000 Hz. There is insufficient evidence, however, to rule out an ototoxic effect at 8000 Hz. Future studies should further evaluate the effect of interferon on auditory function in patients with MS. Neuroscience nurses should monitor their patients' hearing throughout the course of treatment.

P029 - Efficacy and safety of fingolimod treatment in multiple sclerosis: The clinical experience of the AUBMC Multiple Sclerosis Center in Lebanon

Background Fingolimod is the first oral disease-modifying therapy (DMT) approved by the US Food and Drug Administration (FDA) in September 2010 and by the European Medicines Agency (EMA) in March 2011 for the treatment of relapsing-remitting multiple sclerosis (RRMS). The available efficacy and safety data of fingolimod derives from the two completed Phase III clinical trials, FREEDOMS and TRANSFORMS which demonstrated a reduction in the relapse-rate, disability progression and gadolinium-enhancing lesions compared to placebo and intramuscular interferon beta 1a. However, there are still no or few data about the real-world efficacy and safety of fingolimod, at least after one year of treatment in the Middle East region. Objective To describe our clinical experience with fingolimod looking at different outcomes including efficacy, tolerability and safety in multiple sclerosis (MS) patients presenting to our MS Center. Methods MS patients who were treated with fingolimod and visited our AUBMC-MS Center from October 2011 to December 2013 were identified. Demographics, MS disease related variables, first-dose and follow up recorded adverse events and efficacy outcomes were extracted from our medical charts. Main efficacy outcomes were the annualized relapse rate (ARR), the disability progression (EDSS) and the magnetic resonance imaging (MRI) activity. Results Eighty seven RRMS patients who were prescribed fingolimod were included in the analysis. Fifty eight were women and 29 men. Mean disease duration was 6.8±6.1 years and mean EDSS at fingolimod initiation was 2.33±1.4. Eight patients received fingolimod between 3 and 5 months, 26 patients received treatment between 6 and 11 months, 32 patients between 12 and 23 months, and 21 patients >24 months. First dose observation was uneventful in all patients. Within a period of 14.9±8 months, treatment was discontinued in 21 patients (24.4%) due to progression of the disease to secondary progressive MS (n=6), lack of efficacy (n=10), pregnancy (n=1), recurrent infections (n=1), varicella zoster virus (VZV) radiculitis (n=1), and patients' personal decision (n=2). ARR in the year previous to fingolimod treatment was 1.31 and decreased to 0.26 during the overall treatment period. In patients treated with fingolimod for <12 months (n=53), 60.4% were free from EDSS progression and 62.3% were free from MRI activity. Conclusion In our study patients, fingolimod was safe, well tolerated and effective in reducing disease activity and progression of disability. Fingolimod is the first oral disease-modifying therapy (DMT) approved by the US Food and Drug Administration (FDA) in September 2010 and by the European Medicines Agency (EMA) in March 2011 for the treatment of relapsing-remitting multiple sclerosis (RRMS). The available efficacy and safety data of fingolimod derives from the two completed Phase III clinical trials, FREEDOMS and TRANSFORMS which demonstrated a reduction in the relapse-rate, disability progression and gadolinium-enhancing lesions compared to placebo and intramuscular interferon beta 1a. However, there are still no or few data about the real-world efficacy and safety of fingolimod, at least after one year of treatment in the Middle East region. To describe our clinical experience with fingolimod looking at different outcomes including efficacy, tolerability and safety in multiple sclerosis (MS) patients presenting to our MS Center. MS patients who were treated with fingolimod and visited our AUBMC-MS Center from October 2011 to December 2013 were identified. Demographics, MS disease related variables, first-dose and follow up recorded adverse events and efficacy outcomes were extracted from our medical charts. Main efficacy outcomes were the annualized relapse rate (ARR), the disability progression (EDSS) and the magnetic resonance imaging (MRI) activity. Eighty seven RRMS patients who were prescribed fingolimod were included in the analysis. Fifty eight were women and 29 men. Mean disease duration was 6.8±6.1 years and mean EDSS at fingolimod initiation was 2.33±1.4. Eight patients received fingolimod between 3 and 5 months, 26 patients received treatment between 6 and 11 months, 32 patients between 12 and 23 months, and 21 patients >24 months. First dose observation was uneventful in all patients. Within a period of 14.9±8 months, treatment was discontinued in 21 patients (24.4%) due to progression of the disease to secondary progressive MS (n=6), lack of efficacy (n=10), pregnancy (n=1), recurrent infections (n=1), varicella zoster virus (VZV) radiculitis (n=1), and patients' personal decision (n=2). ARR in the year previous to fingolimod treatment was 1.31 and decreased to 0.26 during the overall treatment period. In patients treated with fingolimod for <12 months (n=53), 60.4% were free from EDSS progression and 62.3% were free from MRI activity. In our study patients, fingolimod was safe, well tolerated and effective in reducing disease activity and progression of disability.

Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported. CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced. One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS. Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.

Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome.

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3%) CIS patients at baseline and at the 24months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

Fingolimod versus intramuscular interferon in patient subgroups from TRANSFORMS

In the 12-month phase 3 TRANSFORMS study, fingolimod showed greater efficacy than intramuscular interferon beta (IFNβ)-1a in patients with relapsing-remitting multiple sclerosis (RRMS). This study analyzed fingolimod efficacy compared with IFNβ-1a in patient subgroups from TRANSFORMS. Patients were randomized to receive fingolimod or weekly IM IFNβ-1a for 12 months. Analyses of efficacy included annualized relapse rate (ARR), and magnetic resonance imaging (MRI) measures [gadolinium (Gd)-enhancing T1 lesions, new/newly enlarged (active) T2 lesions, brain volume change]. Subgroups were defined based on demographics, disease characteristics (baseline EDSS score, relapse rate, and MRI parameters), and response to previous therapy. Fingolimod 0.5 mg reduced ARR over 12 months by 32-59 % relative to IFNβ-1a in all subgroups defined by demographic factors or baseline disease characteristics. Fingolimod also reduced the number of new Gd-enhancing lesions, active T2 lesions, and the rate of brain volume loss, versus IFNβ-1a in most (95 %) subgroups. In patients with high disease activity despite IFNβ treatment in the year before study, fingolimod 0.5 mg reduced ARR by 61 % relative to IFNβ-1a. Reductions in lesion counts and brain volume loss also favored fingolimod in these patients. In conclusion, consistently better efficacy was observed for fingolimod compared with IFNβ-1a across different subgroups of patients with RRMS.

Gender effects on intramuscular interferon beta-1a in relapsing–remitting multiple sclerosis: analysis of 1406 patients

Background: We aimed to evaluate effects of gender on efficacy and safety of intramuscular (IM) interferon beta (IFNβ)-1a in patients with relapsing–remitting MS (RRMS) or clinically isolated syndromes (CIS) characteristic of early MS. Methods: Pooled data from 1406 (1027 women; 379 men) patients enrolled in five clinical studies of IM IFNβ-1a were analyzed. One analysis examined data for all patients treated with IM IFNβ-1a from all studies. Separate analyses were conducted of pooled IM IFNβ-1a-treated groups from all studies and pooled IFNβ-1a-treated and placebo-treated patients from the placebo-controlled studies. Outcome measures included time to first relapse, annualized relapse rate, time to disability progression, number of gadolinium-enhanced lesions, adverse events, laboratory evaluations, and neutralizing antibodies. Results: All efficacy assessments indicated similar treatment effects of IM IFNβ-1a in men and women with no significant treatment-by-gender interactions. Women reported more headaches, urinary tract infections, and depression in the analysis; however, these were also common in women who received placebo. Men reported more frequent flu-like symptoms in the placebo-controlled studies only. There were no other differences in the safety profile of IM IFNβ-1a between men and women. Conclusions: We conclude that no significant gender-related differences were found in the efficacy and safety of IM IFNβ-1a in patients with RRMS or CIS.

Chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: treatment update

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy usually respond to immune therapies including steroids and plasma exchange for CIDP and high-dose intravenous immunoglobulins (IVIgs) for both diseases. Other immune therapies have been used to reduce the costs or the side-effects of these therapies, but their efficacy was only recently assessed in randomized controlled trials (RCTs). The prolonged efficacy of IVIg in CIDP has been confirmed in a 48-week RCT. Two other RCTs showed that oral methotrexate or intramuscular interferon beta were not more effective than placebo in improving the efficacy or reducing the dose of IVIg or steroids. In multifocal motor neuropathy, a RCT showed that oral mycophenolate mofetil was not more effective than placebo in increasing the efficacy or reducing the dose of IVIg. Other immune therapies were assessed in open trials in both diseases, but their efficacy remains unclear, even if in some patients a possible efficacy of rituximab was reported. Some preliminary studies suggest that subcutaneous immunoglobulin may be as effective as IVIg in the maintenance therapy of CIDP and multifocal motor neuropathy. After several years of anecdotal reports, a number of RCT have now appeared in CIDP and multifocal motor neuropathy, but their results are still insufficient to support the use of new therapies in these diseases.

Estudio global de adherencia a los tratamientos inmunomoduladores en pacientes con esclerosis múltiple remitente recidivante: resultados a 2 años

Background In this article we report adherence data from the first 2 years in a subset of patients from the Global Adherence Project (GAP; n = 2,648) in Spain. Methods A questionnaire assessing adherence to Disease-modifying therapies (DMTs), was distributed annually to patients and their treating neurologists. Non-adherence was defined as missing a DMT injection or changing a dose in the four weeks prior to completing the survey. Patients signed informed consent and Ethics Committees approved annual follow-ups, visit 1 (V1) and visit 2 (V2) in 15 out of 18 centres in Spain. Results A total of 254 patients were enrolled in Spain. Patients had a mean age of 37.9 years and 70.4% were female, and had been on their treatment for a median time of 28 months, and the overall adherence rate was 85.4%. Patients taking intramuscular interferon beta (IFNB)-1a (Avonex ®) were significantly more adherent (94.6%) compared with patients taking subcutaneous (s.c.) IFNB-1a 22 μg (Rebif ®22) (79.1%; p = 0.0064), s.c. IFNB-1a 44 μg (Rebif ®44) (79.6%; p = 0.0064) and glatiramer acetate (GA) (82.7%; p = 0.0184). At V1 (n = 142), the overall adherence rate was 86.6% and patients on Avonex ® were significantly more adherent than patients on Rebif ®22 (93.9% versus 66.7%; p = 0.0251). At V2 (n = 131), the overall adherence rate was 82.4% (Avonex ®, 87.5%; Rebif ®22, 80%; Rebif ®44, 77.8%; Betaferon ®, 85.2%, and Copaxone ®, 80%) without significant differences. Conclusions Adherence remained high over the first 2 years of the study. It was highest with Avonex ®, being significant on first assessment, after 40.5 months of therapy, on average compared with other DMTs and at year 1 compared with Rebif ®22.

Global Adherence Project to Disease-Modifying Therapies in Patients With Relapsing Multiple Sclerosis: 2-Year Interim Results

Background In this article we report adherence data from the first 2 years in a subset of patients from the Global Adherence Project (GAP; n = 2,648) in Spain. Methods A questionnaire assessing adherence to Disease-modifying therapies (DMTs), was distributed annually to patients and their treating neurologists. Non-adherence was defined as missing a DMT injection or changing a dose in the four weeks prior to completing the survey. Patients signed informed consent and Ethics Committees approved annual follow-ups, visit 1 (V1) and visit 2 (V2) in 15 out of 18 centres in Spain. Results A total of 254 patients were enrolled in Spain. Patients had a mean age of 37.9 years and 70.4% were female, and had been on their treatment for a median time of 28 months, and the overall adherence rate was 85.4%. Patients taking intramuscular interferon beta (IFNB)-1a (Avonex ®) were significantly more adherent (94.6%) compared with patients taking subcutaneous (s.c.) IFNB-1a 22 μg (Rebif ®22) (79.1%; p = 0.0064), s.c. IFNB-1a 44 μg (Rebif ®44) (79.6%; p = 0.0064) and glatiramer acetate (GA) (82.7%; p = 0.0184). At V1 (n = 142), the overall adherence rate was 86.6% and patients on Avonex ® were significantly more adherent than patients on Rebif ®22 (93.9% versus 66.7%; p = 0.0251). At V2 (n = 131), the overall adherence rate was 82.4% (Avonex ®, 87.5%; Rebif ®22, 80%; Rebif ®44, 77.8%; Betaferon ®, 85.2%, and Copaxone ®, 80%) without significant differences. Conclusions Adherence remained high over the first 2 years of the study. It was highest with Avonex ®, being significant on first assessment, after 40.5 months of therapy, on average compared with other DMTs and at year 1 compared with Rebif ®22.

A randomized, blinded, parallel-group, pilot trial of mycophenolate mofetil (CellCept) compared with interferon beta-1a (Avonex) in patients with relapsing-remitting multiple sclerosis

Mycophenolate mofetil (MMF, CellCept®) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex® at 30 mcg) in relapsing-remitting MS (RRMS). We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.

Improvement of health-related quality of life in relapsing remitting multiple sclerosis patients after 2 years of treatment with intramuscular interferon-beta-1a

In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with disability. In 36 neurological practices in the Netherlands (17), Belgium (16), United Kingdom (2) and Luxemburg (1), 284 RRMS patients were treated with intramuscular INFb-1a. Physical and mental domains of HR-QoL were measured by the MS54 Quality of Life (MS54QoL) questionnaire, and disability was assessed by the Multiple Sclerosis Functional Composite (MSFC) (Timed 25-Foot Walk Test [Timed 25-FWT], 9 Hole Peg Test [9-HPT], Paced Auditory Serial Addition Test [PASAT]) at baseline and at months 3, 6, 12, 18 and 24. Expanded Disability Status Scale (EDSS) score was assessed at baseline and month 24. Pearson's correlation coefficients were determined and predefined factors were analyzed for relation to HR-QoL after baseline by stepwise regression analyses on physical and mental scores. 204 patients (71.8%) completed 2 years of treatment. Mean values for MS54QoL increased from 56.6 to 61.0 for physical (p < 0.05) and from 57.2 to 61.1 for mental domain (p = 0.07). Correlations between physical domain and MSFC was -0.40 (p < 0.05), and between mental domain and MSFC -0.24 (p < 0.05). MSFC and EDSS did not change. Increase of physical MS54QoL was associated with lower age, lower EDSS, less time for Timed 25-FWT, and higher PASAT score at baseline. Increase of mental MS54QoL was associated with higher PASAT and lower EDSS. Patients who discontinued INFb had lower physical or mental HR-QoL at baseline. In RRMS patients, 2 years of treatment with intramuscular INFb-1a is associated with an increase in HR-QoL, especially in younger patients with low disability.

Evolución clínica de pacientes con esclerosis múltiple tratados con citostáticos por cáncer

Introduction. The risk of side effects secondary to global and non-specific immune suppression has limited the systematic application of immunosuppressive therapy in multiple sclerosis (MS). However, when a patient with MS develops a cancer, cytostatic drugs as treatment for the neoplastic process may induce improvement not only of the cancer but also of MS. Case reports. We present a series of four women with clinically defined MS and subjected to cytostatic therapy (cisplatin, 5-fluorouracil, leukovorin, adriamycin, tamoxifen and anastrozole) after the development of cancer: two presented breast cancer, one colon cancer, and the fourth parotid gland malignancy. Their clinical and neuroimaging course is described, following chemotherapy for the malignant disease. None of the patients have suffered further MS outbreaks. The four women have improved and remain clinically stable after neoplastic treatment. Magnetic resonance imaging showed persistence of the same lesion burden in three patients, and reduction in the other. At the present one patient receives weekly intramuscular interferon-beta 1a, whereas the other did not received any treatment. Conclusions. Probably there are no specific cytostatics for MS. Immunosuppressive therapy could be a therapeutic option among patients with an aggressive clinical course. © 2009, Revista de Neurologia.

Managing adverse effects of disease-modifying agents used for treatment of multiple sclerosis

ABSTRACTBackground: First-line agents approved in the United States for treatment of relapsing multiple sclerosis (MS) include intramuscular interferon beta (IFNβ)-1a, subcutaneous (SC) IFNβ-1a, SC IFNβ-1b, and SC glatiramer acetate. Intravenous mitoxantrone is the only agent approved for secondary progressive MS, progressive relapsing MS, and worsening relapsing MS. Intravenous natalizumab is approved for relapsing forms of MS generally in patients who have an inadequate response to, or are unable to tolerate, first-line therapies. Corticosteroids are commonly used to treat relapses. This paper reviews the incidence and management of common adverse events (AEs) associated with these treatments.Methods: MEDLINE and EMBASE were searched for clinical trials and other publications between 1985 and 2007 reporting AEs associated with MS therapies, using these search terms: multiple sclerosis, interferon, Avonex, Betaseron, Rebif, glatiramer, copolymer 1, Copaxone, mitoxantrone, natalizumab, adverse events.Results: A class-specific flu-like syndrome associated with IFNβ can be managed through initial dose escalation and administration of analgesics and antipyretics, prophylactically or symptomatically. Injection-site reactions can occur in patients receiving injectable therapies, particularly SC IFNβ or glatiramer acetate. The greatest risk to patients receiving mitoxantrone is cardiotoxicity; thus, the cumulative dose is limited. Allergic reactions occur rarely with natalizumab, and there is a potential risk of progressive multifocal leukoencephalopathy. AEs associated with short-term pulse corticosteroid therapy are usually transient and largely resolve after treatment is completed.Conclusions: To improve adherence to therapy, it is important to educate patients regarding AEs and to manage AEs proactively.

Safety and Tolerability in Relapsing-Remitting Multiple Sclerosis Patients Treated With High-Dose Subcutaneous Interferon-Beta by Rebiject Autoinjection Over a 1-Year Period

Approved multiple sclerosis (MS) treatments include subcutaneous and intramuscular interferon beta (IFN-beta) Patient satisfaction during long-term IFN-beta treatment is crucial. This study investigated the satisfaction of patients with relapsing-remitting MS treated with IFN-beta-1a (Rebif) by the autoinjection system, Rebiject. This prospective observational study recruited subjects with relapsing-remitting MS (n = 76) from 19 neurological centers in Italy who were eligible for subcutaneous IFN-beta-1a treatment either as a first immunomodulatory therapy or as a switch from other treatments. Patients received IFN-beta-1a 44 mug 3 times weekly via the Rebiject system. A questionnaire on the use of Rebiject and the most common adverse effects related to IFN-beta-1a administration was completed monthly under the supervision of trained nurses. Satisfaction with treatment was reported by 80.2% of patients who received at least 1 dose. Advantages reported for the Rebiject system included its convenience (53% of all patients), ease of use (25%), reduced trauma and pain (11% and 6%, respectively), and reduced local skin reactions (5%). No significant changes from baseline were observed regarding the frequency or severity of local reactions. During the 1-year observation of this small cohort, most patients considered the Rebiject system to be convenient, with a third of the patients feeling that the system was easier to use than conventional procedures. Rebiject was also associated with less pain and trauma in some patients. Use of Rebiject may facilitate IFN-beta-1a administration and may lead to an increase in compliance and adherence, thus increasing the effectiveness of treatment.

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28-May 5, 2007

Effect of early interferon beta-1a therapy on conversion to multiple sclerosis in Iranian patients with a first demyelinating event

A new treatment approach to multiple sclerosis (MS) is the initiation of interferon therapy in the early phase of the disease when a patient presents with clinically isolated syndrome. The goal of this study was to assess the effect of early treatment on the risk of conversion to clinically definite MS in Iranian patients. Eligible patients had presented with a first episode of neurological dysfunction suggesting MS within the previous 3 months and had abnormal brain magnetic resonance imaging (MRI). Patients were randomly assigned to receive intramuscular interferon beta 1a 30 mug or placebo once a week for 3 years. Of the 217 patients randomized, 202 patients completed the study; 104 received Avonex and 98 received placebo. Fewer patients converted to clinically definite multiple sclerosis in the treated group than in the placebo group during the study (36.6% vs 58.2%, P < 0.003). The number of active T2-weighted MRI lesions was significantly lower in the treated group. The results of our study, which are consistent with those from western studies, show that treatment at an early stage of MS delays conversion to definite MS and has positive effects on MRI outcomes.

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.