Adherence to interferon-beta treatment and results of therapy switching

doi:10.1016/j.jns.2006.05.075

Journal of the Neurological Sciences

Volume 259, Issues 1–2, 15 August 2007, Pages 104-108

https://doi.org/10.1016/j.jns.2006.05.075 Get rights and content

Abstract

Adherence to long-term therapy has always been a problem in all fields of medicine. In multiple sclerosis (MS), treatment consists of parenteral administration of immune-modulating drugs once or several times weekly for an as yet undetermined length of time. Different studies on the MS patients' compliance showed that the most frequent cause of stopping treatment is the perceived lack of efficacy and that most treatment withdrawals occur during the first year of treatment. A trial aimed to identify the minimum effective IFNβ dose showed that some patients had disease activity after switching to a lower IFNβ dose. OPTIMS (OPTimization of Interferon dose for MS study) was a multicenter study, involving 24 Italian MS centers, 216 patients, aimed to identify a treatment response indicator allowing the early identification of poorly responding patients. A single active scan during the first 6 months of IFN treatment had a significant positive predictability of 59% (95% confidence interval, 41–76; p = 0.05) on the presence of clinical signs of disease activity during the further 2-year follow-up.

Introduction

Adherence to long-term therapy has always been a problem in all fields of medicine and among different chronic diseases a generally quite high percentage of poor-compliant patients is well documented. In MS this percentage is 15–40% [1], [2], [3].

Three β interferons (IFNβ) have been approved for MS treatment: subcutaneous (SC) IFNβ-1b, SC IFNβ-1a, and intramuscular (IM) IFNβ-1a. Patients meeting the treatment criteria can expect a 30% decrease in relapse rate over a 2-year period [4]. The effects on disability are more questionable, although sustained disability progression is probably slowed [4]. MS is a life-long disease and no definitive cure is nowadays available. This means that any therapy should be continued for an as yet undetermined length of time. Being required to administer a drug once or several times per week or many years by parenteral administrations can cause frustration, and some patients may find it hard to cope with such a treatment regimen over the long term.

The biggest problem of a poor compliance to the treatment, as in any other chronic disease, consists in its leading patients to stop the treatment. In MS, the causes of stopping treatment are different: side effects (flu-like reactions, depression, headache, laboratory abnormalities and fatigue more frequently), perceived lack of efficacy, missed disease improvement, or disease worsening.

The natural consequence of stopping treatment results in failing the common goal of chronic disease treatment which consists in preventing the progression or the worsening of the disease. As clinicians we should encourage our patients in continuing therapy in order to prevent the consequences of a worsening health condition both on the patients themselves as well as on our public health care system.

Section snippets

MS patients' compliance to IFNβ treatment

Different studies on the MS patients' compliance and on the most frequent causes of stopping treatment have been published (Table 1).

A Canadian retrospective chart review has been conducted on all patients of the University of British Columbia MS clinic prescribed an IFNβ from July 1995 to June 2001 [5]. Eight hundred and forty-six patients started IFNβ treatment between July 1995 and June 2001. Of 203 patients followed for at least 3 years 79 (39%) patients stopped treatment prematurely. The

Is it possible to reduce IFNβ dose and frequency of administration?

Since many patients decide to reduce or stop IFNβ treatment we designed a trial aimed to identify the minimum effective IFNβ dose. Twenty-seven RR MS patients on chronic IFNβ-1b treatment were randomized either to continue with the same IFNβ-1b dose (250 μg, SC, every other day [EOD]) or to progressively reduce both the dose and the number of administrations being gradually switched to IM once a week IFNβ-1a. To be included in the study, patients had to be diagnosed with definite RR MS, with an

Looking for an easy-to-use treatment response indicator

Since the main reason for stopping treatment is the perceived lack of efficacy, a reliable treatment response indicator could improve patients' compliance. It must allow treating neurologists to early identify poorly responding patients and to tailor treatment to each patient's needs. Table 2 shows treatment response indicators which have been recently tested. They have been validated in small sample trials and are based on laboratory techniques difficult to be used in the routine everyday work

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Understanding treatment decisions from the perspective of people with relapsing remitting multiple Sclerosis: A critical interpretive synthesis
2019, Multiple Sclerosis and Related Disorders
Citation Excerpt :
Studies exploring reasons why PwRRMS stop/switch treatments frequently use the term ‘DMT efficacy’ but do not explore what type of efficacy that is i.e. more relapses, decreased functionality, lesions, or a combination. In fact, some argue that DMT efficacy is a subjective term that depends on individuals’ health perceptions [Clerico et al., 2007]. While individual heterogeneity is inherent to RRMS, our review showed that PwRRMS’ understanding of DMTs is usually mediated by five factors.
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system that mainly affects young adults. While there is no cure for MS, disease modifying treatments (DMTs) reduce the relapse rate and partial accrual of disability. More effective DMTs may have higher risks including life-threatening infections or secondary autoimmunity. The complexity and novelty of available treatments cause challenges for clinicians when prescribing treatments and for people with MS (PwMS) when deciding what trade-offs they are willing and ready to make.
To explore the experience of people with relapsing remitting MS (PwRRMS) and their perspectives in choosing treatments.
Critical interpretive synthesis was employed to review and synthesis the published literature. Eighty-three publications were selected in a multi-step systematic process.
Findings are presented in four interrelated areas: the influence of the clinical evidence-base in decision making; the meaning of DMT efficacy for PwRRMS; the influence of models of decision-making and information acquisition practices in PwRRMS; and the importance of psychosocial dimensions in DMT decision making. Synthesis of the findings revealed that alongside medical and individual reasoning, contextual circumstances play an important role in making treatment decisions.
This review identifies and explains the importance of diverse contextual circumstances (clinical, social, psychological) that are important for PwRRMS when making treatment decisions. The findings demonstrate the importance of eliciting, understanding and addressing such contextual factors.
Currently approved and emerging oral therapies in multiple sclerosis: An update for the ophthalmologist
2016, Survey of Ophthalmology
Citation Excerpt :
For nearly 2 decades after the introduction of the first FDA-approved MS therapy, all the available DMDs were administered subcutaneously, intramuscularly, or intravenously. Although healthcare providers and patients welcomed the addition of more effective DMDs, the injection component resulted in problems with therapy adherence contributing to reduced efficacy.21 In addition, with multiple therapies falling into the category of interferon β, agents with novel mechanisms of action were needed.
Although our understanding of multiple sclerosis (MS) has grown substantially, its cause remains unknown. Nonetheless, in the past 3 decades, there have been tremendous advancements in the development of disease-modifying drugs (DMDs). In July 1993, the United States Food and Drug Administration approved the first disease-modifying drug—interferon β– and there are currently 13 medications approved for use in relapsing MS. All the early medications are administered either as a subcutaneous or intramuscular injection, and despite the clinical efficacy and safety of these medications, many patients were hampered by the inconvenience of injections and injection-related side effects. In September 2010, the first oral DMD—fingolimod—was approved. Since then, 2 additional oral DMDs (teriflunomide and dimethyl fumarate) have been approved, and several other oral medications are being evaluated in extensive MS development programs. Because of frequent ocular involvement, ophthalmologists are often involved in the care of MS patients and therefore need to be aware of the current treatment regimens prescribed by neurologists, some of which can have significant ophthalmic adverse events. We update the current advancements in the treatment of MS and discuss the published clinical data on the efficacy and safety of the currently approved and emerging oral therapies in MS.
Discontinuation and long-term adherence to beta interferon therapy in patients with multiple sclerosis
2012, Farmacia Hospitalaria
Estudiar la frecuencia de discontinuación y el grado de adherencia en la primera línea de tratamiento con interferón beta (INFβ) en pacientes con esclerosis múltiple (EM), identificando sus causas y factores asociados.
Estudio observacional retrospectivo que incluyó pacientes con EM clínicamente definida en tratamiento con INFβ durante el año 2001 en el área de pacientes externos de un servicio de farmacia hospitalaria. Se realizó un seguimiento desde el inicio del tratamiento hasta finales del año 2006. Las fuentes de datos utilizadas fueron la base de datos informatizada del área de pacientes externos, la historia clínica y los protocolos de solicitud de inicio y seguimiento de tratamiento para la EM. Se recopiló información sobre las características basales del paciente, tratamiento y continuidad del mismo.
Se incluyeron 131 pacientes, a los que se les realizó un seguimiento medio de 7,4 ± 2,6 años. El 64,1% fueron tratados con un solo fármaco durante todo el estudio. A los 2 años del inicio de la terapia con INFβ habían discontinuado la terapia el 9,9%, a los 5 años el 41,2% y a los 8 años y medio el 58,7%. Se mantenían más tiempo en tratamiento los hombres, pacientes con EM recurrente-remitente y tratados con INFβ1a-im, si bien solo fue significativo en los pacientes con 10 años o menos de evolución de la enfermedad al inicio del tratamiento. Las causas mayoritarias de discontinuación fueron la falta de efectividad (38,8%) y la aparición de efectos adversos (32,8%). Los pacientes adherentes discontinuaron menos el tratamiento (55,8 vs 75%).
La continuidad a largo plazo en el tratamiento de la EM se ve reducida principalmente por la falta de efectividad y los efectos adversos. Una aproximación a la perspectiva del paciente puede ayudar a identificar aquellos con mayor riesgo de falta de adherencia para ayudar a optimizar la terapia.
To determine discontinuation rate and degree of adherence to first-line treatment with interferon-beta (INFβ) in patients with multiple sclerosis (MS), identifying causes and associated factors.
A retrospective observational study that included patients with MS treated with INFβ during 2001. The patients were followed-up from the beginning of treatment until the end of 2006. The data sources used were a computer database compiled in the outpatients’ area, medical records and application protocols for beginning and monitoring treatment for MS. Patient characteristics at baseline, treatment and continuity were included in the information collected.
The study included 131 patients. Mean follow-up was 74 ± 26 years. 641% of the patients were treated with only one drug during the study. At 2 years follow-up 99% of patients had discontinued INFβ therapy and at 5 years 412% had done so. Men, patients with relapsing-remitting MS and those treated with INFβ1a i.m. continued treatment for a longer period, but this was statistically significant only in patients with 10 years or less of disease progression at the beginning of therapy. Main causes of discontinuation were lack of efficacy (388%) and adverse effects (328%). Compliant patients presented lower discontinuation rates (558% vs. 75%).
treatment of MS patients with IFNβ is discontinued mainly due to lack of efficacy and adverse effects. Greater understanding of patients’ views can help to identify those at greatest risk of lack of adherence, thereby helping to improve treatment.
Effect of an educational intervention based on the theory of planned behavior on improving medication adherence in patients with multiple sclerosis treated with injectable disease-modifying drugs: randomized controlled trial
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Adherence to interferon-beta treatment and results of therapy switching

Abstract

Introduction

Section snippets

MS patients' compliance to IFNβ treatment

Is it possible to reduce IFNβ dose and frequency of administration?

Looking for an easy-to-use treatment response indicator

J Neurol Sci

J Neuroimmunol

Lancet

J Neuroimmunol

Long term interferon-β treatment for multiple sclerosis

Neurol Sci

Twenty-four-months comparison of immunomodulatory treatments—a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone®)

Eur J Neurol

A post-marketing study on interferon β-1b and 1a treatment in relapsing–remitting multiple sclerosis: different response in drop-outs and treated patients

J Neurol Neurosurg Psychiatry

Neurology

Interrupted therapy: stopping and switching of the beta-interferons prescribed for MS

Neurology

Factors related with treatment adherence to interferon beta and glatiramer acetate therapy in multiple sclerosis

Mult Scler

Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patterns

Mult Scler