Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of                 an Italian co-operative study

Objective: Immunomodulatory drugs (IDs) (interferon beta (IFNβ) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing-remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNβ and GA in MS patients treated before 16 years of age. Methods: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). Results: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNβ-1a once weekly (Avonex), 18 with IFNβ three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNβ), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNβ was stopped in six cases: in four because of inefficacy and in two cases because of side effects. Conclusions: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNβ, but were well tolerated in most cases.

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Clinical characteristics of progressive relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1059oa ◽

2004 ◽

Vol 10 (4) ◽

pp. 451-454 ◽

Cited By ~ 17

Author(s):

M J Tullman ◽

R J Oshinsky ◽

F D Lublin ◽

G R Cutter

Keyword(s):

Multiple Sclerosis ◽

Relapse Rate ◽

Clinical Characteristics ◽

Age At Onset ◽

Retrospective Chart Review ◽

Disability Status ◽

Acute Exacerbations ◽

Annualized Relapse Rate ◽

The Mean ◽

Relapsing Multiple Sclerosis

Objective: Patients with progressive relapsing (PR) multiple sclerosis (MS) may accrue disability by incomplete recovery from acute exacerbations and by ongoing deterioration. In primary progressive (PP) MS, disability accumulates solely by continuous decline. Because it is the least common form of MS, there is scant information regarding the clinical characteristics of PRMS, but relapses are reportedly uncommon. The purpose of this study is to describe the clinical features of a cohort of patients with PRMS. Methods: A retrospective chart review of 16 patients diagnosed with PRMS at two academic MS centres over a four-year period. Results: Nine men and seven women had PRMS. The mean age at onset was 35.19/11.2 years. The most common presenting symptom was a progressive myelopathy. The mean disease duration was 10.19/8.5 years and the average time to first exacerbation was 4.19/3.7 years. Patients had an average of 2.89/2.3 relapses with an annualized relapse rate of 0.69/0.8. Time to Expanded Disability Status Scale (EDSS) 6.0 was strongly associated with time to first exacerbation. Although there was no correlation between the number of relapses and time to EDSS 6.0, there was a modest inverse relation between time to EDSS 6.0 and annualized relapse rate. Conclusions: Relapses in PRMS may occur more often than previously described and disability may accumulate more rapidly in PRMS than in PPMS. We suggest differentiating between these two forms of MS.

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Clinical trials in relapsing-remitting multiple sclerosis (a new proposal for dealing with basic problems and restrictions)

Journal of Medical Science ◽

10.20883/medical.e24 ◽

2015 ◽

Vol 84 (2) ◽

pp. 104-106

Author(s):

Mieczyslaw Wender ◽

Grazyna Michalowska-Wender

Keyword(s):

Multiple Sclerosis ◽

Glatiramer Acetate ◽

Relapse Rate ◽

Interferon Beta ◽

Therapy Group ◽

Current Standard ◽

Reference Drug ◽

Disease Modifying Drugs ◽

Double Blinded ◽

Relapsing Remitting Multiple Sclerosis

The natural course of multiple sclerosis is characterized by a high variability of pattern, relapse rate and different progression indices. They also present a dramatic impact on the interpretation of treatment trials. Older reports, based on uncontrolled observations are therefore of little value. Currently it is generally accepted that a proper treatment trial should be double blinded and, although probably controversial, that it should be compared with a group of MS patients treated with placebo. Such an approach would be easily acceptable to prove the effectiveness of recently discovered disease modifying drugs. We know that current standard methods of therapy with interferon beta or glatiramer acetate are able to decrease the relapse rate at least by one third, to elongate the intervals between the relapses and to decrease the progression indices. Currently MS is considered a generalized degenerative disease. The lesions are persistent, therefore immunomodulatory treatment has to be started as early as possible. An alternative approach, somewhat suggestive for the use of placebo trials, seems to be a comparison of proposed new drug therapy group with a group of patients treated with a generally accepted reference drug, such as interferon beta or glatiramer acetate, including all clinical and MRI measures.

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Cortical Excitability Measures May Predict Clinical Response to Fampridine in Patients with Multiple Sclerosis and Gait Impairment

Brain Sciences ◽

10.3390/brainsci9120357 ◽

2019 ◽

Vol 9 (12) ◽

pp. 357 ◽

Cited By ~ 3

Author(s):

Rechdi Ahdab ◽

Madiha M. Shatila ◽

Abed Rahman Shatila ◽

George Khazen ◽

Joumana Freiha ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prospective Observational Study ◽

Cortical Excitability ◽

Exclusion Criteria ◽

Gait Impairment ◽

Disease Modifying Drugs ◽

Resting Motor Threshold ◽

Disability Status ◽

The Mean ◽

To Receive

Background: Most multiple sclerosis (MS) patients will develop walking limitations during the disease. Sustained-release oral fampridine is the only approved drug that will improve gait in a subset of MS patients. Objectives: (1) Evaluate fampridine cortical excitability effect in MS patients with gait disability. (2) Investigate whether cortical excitability changes can predict the therapeutic response to fampridine. Method: This prospective observational study enrolled 20 adult patients with MS and gait impairment planned to receive fampridine 10 mg twice daily for two consecutive weeks. Exclusion criteria included: Recent relapse (<3 months), modification of disease modifying drugs (<6 months), or Expanded Disability Status Scale (EDSS) score >7. Neurological examination, timed 25-foot walk test (T25wt), EDSS, and cortical excitability studies were performed upon inclusion and 14 days after initiation of fampridine. Results: After treatment, the mean improvement of T25wt (ΔT25wt) was 4.9 s. Significant enhancement of intra-cortical facilitation was observed (139% versus 241%, p = 0.01) following treatment. A positive correlation was found between baseline resting motor threshold (rMT) and both EDSS (r = 0.57; p < 0.01) and ΔT25wt (r = 0.57, p = 0.01). rMT above 52% of the maximal stimulator output was found to be a good predictor of a favorable response to fampridine (accuracy: 75%). Discussion: Fampridine was found to have a significant modulatory effect on the cerebral cortex, demonstrated by an increase in excitatory intracortical processes as unveiled by paired-pulse transcranial magnetic stimulation. rMT could be useful in selecting patients likely to experience a favorable response to fampridine.

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Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756285614555335 ◽

2014 ◽

Vol 7 (6) ◽

pp. 263-275 ◽

Cited By ~ 48

Author(s):

Kathrin S. Utz ◽

Jana Hoog ◽

Andreas Wentrup ◽

Sebastian Berg ◽

Alexandra Lämmer ◽

...

Keyword(s):

Multiple Sclerosis ◽

Side Effects ◽

Conjoint Analysis ◽

Patient Preferences ◽

Route Of Administration ◽

Treatment Preference ◽

Treatment Preferences ◽

Treatment Frequency ◽

Disease Modifying Drugs ◽

Disease Modifying

Objectives: With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients’ implicit preferences for oral versus parenteral DMTs and identified factors influencing patients’ treatment preference. Methods: Patients with relapsing–remitting MS ( n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios. Based on this questionnaire a choice-based conjoint analysis was conducted. Results: Treatment frequency and route of administration showed a stronger influence on patient preference compared with frequency of mild side effects. The latter attribute was more important for treatment-naïve patients compared with DMT-experienced patients. The higher the Extended Disability Status Scale score, the more likely pills, and the less likely fewer side effects were preferred. Pills were preferred over injections by 93% of patients, when treatment frequency and frequency of side effects were held constant. However, preference switched to injections when pills had to be taken three times daily and injections only once per week. Injections were also preferred when pills were associated with frequent side effects. Conclusions: Our results suggest that route of administration and treatment frequency play an important role in the patients’ preference for a given DMT.

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Disease-Modifying Drugs Reduce Cortical Lesion Accumulation and Atrophy Progression in Relapsing-Remitting Multiple Sclerosis: Results from a 48-Month Extension Study

Multiple Sclerosis International ◽

10.1155/2015/369348 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Francesca Rinaldi ◽

Paola Perini ◽

Matteo Atzori ◽

Alice Favaretto ◽

Dario Seppi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Glatiramer Acetate ◽

Reference Population ◽

Cortical Atrophy ◽

Cortical Lesion ◽

Disease Modifying Drugs ◽

Relapsing Remitting ◽

The Mean ◽

Disease Modifying ◽

Relapsing Remitting Multiple Sclerosis

Cortical lesions (CLs) and atrophy are pivotal in multiple sclerosis (MS) pathology. This study determined the effect of disease modifying drugs (DMDs) on CL development and cortical atrophy progression in patients with relapsing-remitting MS (RRMS) over 48 months. Patients (n=165) were randomized to sc IFNβ-1a 44 μg, im IFNβ-1a 30 μg, or glatiramer acetate 20 mg. The reference population comprised 50 DMD-untreated patients with RRMS. After 24 months, 43 of the untreated patients switched to DMDs. The four groups of patients were followed up for an additional 24 months. At 48 months the mean standard deviation number of new CLs was significantly lower in patients treated with sc IFNβ-1a (1.4 ± 1.0, range 0–5) compared with im IFNβ-1a (2.3 ± 1.3, range 0–6,P=0.004) and glatiramer acetate (2.2 ± 1.5, range 0–7,P=0.03). Significant reductions in CL accumulation and new white matter and gadolinium-enhancing lesions were also observed in the 43 patients who switched to DMDs after 24 months, compared with the 24 months of no treatment. Concluding, this study confirms that DMDs significantly reduce CL development and cortical atrophy progression compared with no treatment.

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The Impact of Educational Package on Nursing Students' Knowledge towards Fertility Preservation, a Quasi-Experimental Study

Internal Medicine And Medical Investigation Journal ◽

10.24200/imminv.v4i2.222 ◽

2019 ◽

Vol 4 (2) ◽

Author(s):

Nastaran Rafiei ◽

Simin Esmaeilpour Zanjani ◽

Kajal Khodamoradi

Keyword(s):

Nursing Students ◽

Side Effects ◽

Fertility Preservation ◽

Care Providers ◽

Patients With Cancer ◽

Educational Package ◽

Significant Difference ◽

Quasi Experimental ◽

The Mean ◽

The Impact

Background: Recent advances in diagnosis and treatment of cancers have resulted in survival improvement in young patients with cancer. Given the side effects of cancer treatments on the function of the reproductive system, health care providers need to be educated about the side effects of cancer treatment and fertility preservation. The aim of this study was to explore the effect of education on nursing students' knowledge towards fertility preservation methods in patients with cancer. Methodology: This was a quasi-experimental one-group pre-test post-test research study that was carried out by the nursing faculty at Islamic Azad University of Tonekabon in 2018. Data was collected through a two-part questionnaire, including demographic characteristics and 32 questions about the knowledge of fertility preservation in patients with cancer. The study intervention was an educational package which includes 8 sessions of small group education, planning questions, and a booklet. Students were asked to complete the questionnaire before starting an educational session and again two weeks after the last session. Results: The difference in the mean score of the nursing students’ knowledge before and after the educational package intervention was significant (P= 0.0001). Also, the knowledge rank of nursing students after the intervention was significantly better than before (P = 0.0001). There was a significant difference between the mean score of knowledge based on gender (0.0001), marital status (0.0001) and residency (0.0001). Conclusion: In conclusion, educational intervention towards fertility preservation had a positive effect on nursing students’ knowledge. Therefore, the importance of considering this new approach to fertility preservation in patients with cancer should be considered in the nursing curriculum as they consider as the main resource of the medical information to the patients

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Treatment of Multiple Sclerosis With Teriflunomide. Multicenter Study of Real Clinical Practice in the Valencian Community-Spain

Frontiers in Neurology ◽

10.3389/fneur.2021.727586 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lamberto Landete ◽

Francisco Pérez-Miralles ◽

Sara García ◽

Antonio Belenguer ◽

Francisco Gascón ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Practice ◽

Relapse Rate ◽

Multicenter Study ◽

Oligoclonal Bands ◽

Patient Profile ◽

The Mean ◽

Pre Treatment ◽

Real Clinical Practice

Introduction: We have different treatment alternatives for relapsing-remitting multiple sclerosis–RRMS–within the so-called platform drugs. It would be desirable to know the ideal drug for each patient. Real clinical practice studies provide us with data on drug efficacy in the medium and long term, safety beyond clinical trials, and can help us to know the patient profile appropriate for each therapy.Material and Methods: An observational multicenter study of real clinical practice in patients with RRMS who were treated with teriflunomide in the Valencian Community, since teriflunomide was authorized in Spain. The database created for this study collects retrospectively patients followed prospectively in the MS clinics.Objectives: To analyze the efficacy and safety of teriflunomide treatment in patients with RRMS under the conditions of real clinical practice, and to identify a patient profile responding to the treatment.Results: We obtained data from 340 patients who received at least one dose of 14 mg teriflunomide. The patients were 69.4% female to 30.6% male, had a mean age of 46.4 years, and a mean time of progression of MS of 11.5 years. The mean pre-teriflunomide relapse rate was 0.4 years, the mean EDSS scorewas 1.98, IgG Oligoclonal bands were present in the CSF of 66.2% of the patients, IgM Oligoclonal bands were present in 46.9%, and the mean number of gadolinium-enhancing lesions was 1.07 lesions per patient at the beginning of treatment. The average number of treatments previously received was 1.04, and 28.53% were naïve. After a follow-up of up to 4 years, a reduction in the annualized and cumulative annualized relapse rate was observed in the first year, in the second year, and in the third year, compared to the pre-treatment year. The EDSS scores were stabilized throughout the follow-up. Likewise, there was a reduction in gadolinium-enhancing lesions in the 1st and 2nd years compared to the pre-treatment period. Applying different generalized multiple linear regression models, we identified a profile of a responding patient to teriflunomide as a male without IgM oligoclonal bands in the CSF, a previous EDSS score of <3, and more than 5 years duration of MS.

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The Combined Effect of Nursing Support and Adverse Event Mitigation on Adherence to Interferon Beta-1b Therapy in Early Multiple Sclerosis

International Journal of MS Care ◽

10.7224/1537-2073-14.4.198 ◽

2012 ◽

Vol 14 (4) ◽

pp. 198-208 ◽

Cited By ~ 3

Author(s):

Suhayl Dhib-Jalbut ◽

Clyde Markowitz ◽

Payal Patel ◽

Francis Boateng ◽

Mark Rametta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Adverse Event ◽

Interferon Beta ◽

Combined Effect ◽

Adverse Event Rate ◽

Dose Titration ◽

Nursing Support ◽

The Mean ◽

The Impact ◽

Mean Compliance

There is limited clinical evidence on the impact of nurse support and adverse event (AE) mitigation techniques on adherence to interferon beta-1b (IFNβ-1b) therapy in multiple sclerosis (MS) in a real-world setting. The aim of the Success of Titration, analgesics, and BETA nurse support on Acceptance Rates in MS Treatment (START) trial was to assess the combined effect of titration, analgesics, and BETA (Betaseron Education, Training, Assistance) nurse support on adherence to IFNβ-1b therapy in patients with early-onset MS and to evaluate safety. Participants were instructed to titrate IFNβ-1b and use analgesics to minimize flu-like symptoms. All received BETA nurse follow-up at frequent intervals: live training, two telephone calls during the first month of therapy, and monthly calls thereafter. Participants were considered adherent if they took at least 75% of the total prescribed doses over 12 months (≥75% compliance). Safety was monitored via reported AEs and laboratory test results. Participants who took at least one IFNβ-1b dose over 12 months were analyzed (N = 104); 73.8% of participants completed the study. The mean age of participants was 37.2 years; 72.1% were women and 78.8% were white. Ninety participants had relapsing-remitting MS and 14 had clinically isolated syndrome. The mean compliance rate, reported for 96 participants with complete dose interruption records, was 84.4%. At 12 months, 78.1% of participants were considered adherent. The serious adverse event rate was 9.6%; most events were unrelated to therapy. Thus in the START study, in which participants received nursing support combined with dose titration and use of analgesics, the majority of participants were adherent to therapy.

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Neurorehabilitation in Multiple Sclerosis – Resilience in Practice

European Neurological Review ◽

10.17925/enr.2017.12.01.31 ◽

2017 ◽

Vol 12 (01) ◽

pp. 31 ◽

Cited By ~ 2

Author(s):

Jürg Kesselring ◽

Keyword(s):

Multiple Sclerosis ◽

Best Practice ◽

Healthcare Providers ◽

Brain Regions ◽

Standards Of Care ◽

Key Factors ◽

Disease Modifying Drugs ◽

Randomised Controlled ◽

The Impact ◽

The Brain

In recent years, enormous strides have been made in increasing the range and efficacy of disease-modifying drugs available for the treatment of multiple sclerosis (MS) in its early and remitting stages, and more continue to emerge. Another equally important concept of successful treatment of MS is neurorehabilitation, which must be pursued alongside these medications. Key factors that contribute to the impact of neurorehabilitation include resilience and neuroplasticity. In the former, components such as nutrition, self-belief and physical activity provide a stronger response to the disease and improved responses to treatment. Neuroplasticity is the capacity of the brain to establish new neuronal networks after lesion damage has occurred and distant brain regions assume control of lost functions. In MS, it is vital that each patient is treated by a coordinated multidisciplinary team. This enables all aspects of the disease including problems with mobility, gait, bladder/bowel disturbances, fatigue and depression to be effectively treated. It is also important that the treating team adopts current best practice and provides internationally agreed standards of care. A further vital aspect of MS management is patient engagement, in which individuals are fully involved and are encouraged to strive and put effort into meeting treatment goals. In this approach, healthcare providers become motivators and patients need less intervention and consume fewer resources. Numerous interventions that promote neurorehabilitation are available, though evidence to support their use is limited by a lack of data from large randomised controlled trials. Combining interventions that promote neurorehabilitation with newer, more effective treatments creates a promising potential to substantially improve the outlook for patients at all stages of MS.

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Effectiveness Of Fiberoptic Phototherapy Compared To Conventional Phototherapy In Treating Hyperbilirubinemia Amongst Term Neonates: A Randomized Controlled Trial

10.21203/rs.3.rs-36655/v2 ◽

2020 ◽

Author(s):

Helvi Ndeshihala Joel ◽

Deborah Mchaile ◽

Rune Philemon ◽

Ronald Mbwasi ◽

Levina Msuya

Keyword(s):

Randomized Controlled Trial ◽

Side Effects ◽

Blue Light ◽

White Light ◽

Treatment Duration ◽

Controlled Trial ◽

Reduction Rate ◽

Term Neonates ◽

Randomized Controlled ◽

The Mean

Abstract Background: Neonatal jaundice is one of the most common problems in newborns. Effective treatment of jaundice requires therapeutic intervention with phototherapy. Over recent years, several studies reported fiberoptic phototherapy to be less effective than conventional phototherapy in term neonates. Our study aimed to compare the effectiveness of fiberoptic phototherapy with a larger illuminated area and higher irradiance to conventional phototherapy methods. Methods: This was a randomized controlled trial conducted at Kilimanjaro Christian Medical Centre (KCMC). A total of 41 term neonates, less than 7 days of age with unconjugated hyperbilirubinemia were randomized. Thirteen (13) newborns were allocated to receive fiberoptic phototherapy, 13 to blue light conventional phototherapy and 15 to white light conventional phototherapy. Effectiveness was assessed by comparing the duration of phototherapy, bilirubin reduction rate and side effects of treatment. The data was analyzed with the independent t-test.Results: The mean overall bilirubin reduction rate was comparable in the fiberoptic phototherapy group (0.74%/h) and the blue light conventional phototherapy group (0.84%/h), with no statistically significant difference (p-value 0.124). However, white light conventional phototherapy had a significantly lower mean overall bilirubin reduction rate (0.29%/h) as compared to fiberoptic phototherapy (p-value <0.001). The mean treatment duration of phototherapy was 69 h, 68 h and 90 h in the fiberoptic, blue light conventional and white light conventional phototherapy groups respectively. Side effects such as loose stool and skin rash were noted in some participants who received conventional phototherapy. No side effects of treatment were noted in the fiberoptic phototherapy group.Conclusion: The effectiveness of fiberoptic PT and blue light conventional PT were comparable in terms of bilirubin reduction rate and treatment duration, whereas fiberoptic phototherapy was more effective than white light conventional PT, with a significantly lower bilirubin reduction rate and treatment duration. Fiberoptic phototherapy may mitigate side effects caused by conventional phototherapy.Trial registration: The Pan African Clinical Trial Registry, PACTR202004723570110. Registered 22nd April 2020- Retrospectively registered, http://www.pactr.org/

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