Injectable Disease-modifying Drugs Research Articles

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

BackgroundAdherence to prescribed treatment in chronic diseases, as occurs in multiple sclerosis (MS), is a critical factor for a successful therapeutic response. This study aimed to investigate the effect of educational program based on Theory of Planned Behavior (TPB) on treatment adherence in patients with multiple sclerosis (MS) receiving injectable immunomodulatory drugs.MethodsThe present study is an educational randomized controlled trial research that was conducted on 100 patients with MS who had gone to MS clinic in Tehran city (Iran). The samples were randomly assigned to the intervention (N = 50) and control groups (N = 50). Data collection instrument was a researcher-made questionnaire based on TPB. Then, educational program was performed for the intervention group through four educational sessions. After three months, data collection was repeated for the two groups and data were analyzed.ResultsThe knowledge and performance of the intervention group on treatment adherence drugs increased from 56.25 ± 20.3 to 78.31 ± 15.57 and 56.22 ± 5.76 to 71.62 ± 12.01 after the education respectively (p < 0.001). The mean of construct of TPB in the intervention group also increased after the intervention (p < 0.05).ConclusionApplying the TPB model proved is very effective in developing an educational program for patients with MS, to enhance treatment adherence drugs. Besides such programs, follow-up education for controlling and monitoring are highly recommended.Trial registrationThis trial has been registered at Iranian Registry of Clinical Trials, IRCT20210808052109N1. Prospectively registered at 12-Aug-2021, (12/8/2021) available at: URL: https://en.irct.ir/trial/57994

Comparison of the Total Side Effects of Injectable Disease-Modifying Drugs for the First-line Treatment of Relapsing-Remitting Multiple Sclerosis

Background: Physicians generally prescribe disease-modifying drugs (DMDs) to reduce the frequency and severity of relapses in multiple sclerosis (MS). The frequency and severity of side effects are important factors that can affect drug choice. The main purpose of this analysis was to evaluate the side effects of different types of first-line injectable DMDs and determine which drug has more complications, and which drug has the most drug discontinuation rates due to severe side effects. Methods: Four groups of injectable DMDs were compared in 386 relapsing-remitting MS (RRMS) patients in the range of 15-60 years who were controlled with these drugs for at least two years (2017-2019) and had the Expanded Disability Status Scale (EDSS) from 0 to 5 without underlying heart and liver diseases. Eventually, the frequency of side effects was determined for each group, and the collected data were compared in each treatment group. Results: In the present study, 31% of patients had no complications. Most of the reported complications (68.25%) were mild in severity, and only 15.5% of the patients discontinued their therapy. Conclusion: The findings recommend that the side effects of different DMDs used for RRMS should be studied more comprehensively in clinical and post-marketing trials. Additionally, physicians should take note of these side effects of DMDs in their prescriptions to increase patients’ adherence to therapy.

A Study of Suboptimally Controlled Participants Previously Taking Injectable Disease-modifying Drugs (DMDs) for Relapsing Forms of Multiple Sclerosis (RMS)

A Study of Suboptimally Controlled Participants Previously Taking Injectable Disease-modifying Drugs (DMDs) for Relapsing Forms of Multiple Sclerosis (RMS)

Utilization Patterns of Oral Disease-Modifying Drugs in Commercially Insured Patients with Multiple Sclerosis.

The approval of new oral disease-modifying drugs (DMDs), such as fingolimod, dimethyl fumarate (DMF), and teriflunamide, has considerably expanded treatment options for relapsing forms of multiple sclerosis (MS). However, data describing the use of these agents in routine clinical practice are limited. To describe time trends and identify factors associated with oral DMD treatment initiation and switching among individuals with MS. Using data from a large sample of commercially insured patients, we evaluated changes over time in the proportion of MS patients who initiated treatment with an oral DMD and who switched from an injectable DMD to an oral DMD between 2009 and 2014 in the United States. We evaluated predictors of oral DMD use using conditional logistic regression in 2 groups matched on calendar time: oral DMD initiators matched to injectable DMDs initiators and oral DMD switchers matched to those who switched to a second injectable DMD. Our cohort included 7,576 individuals who initiated a DMD and 1,342 who switched DMDs, of which oral DMDs accounted for 6% and 39%, respectively. Oral DMD initiation and switching steadily increased from 5% to 16% and 35% to 84%, respectively, between 2011 and 2014, with DMF being the most commonly used agent. Of the potential predictors with clinical significance, a recent neurologist consultation (OR = 1.60; 95% CI = 1.20-2.15) and emergency department visit (OR = 1.43; 95% CI = 1.01-2.01) were significantly associated with oral DMD initiation. History of depression was noted to be a potential predictor of oral DMD initiation; however, the estimate for this predictor did not reach statistical significance (OR = 1.35; 95% CI = 0.99-1.84). No clinically relevant factors measured in our data were associated with switching to an oral DMD. Oral DMDs were found to be routinely used as second-line treatment. However, we identified few factors predictive of oral DMD initiation or switching, which implies that their selection is driven by patient and/or physician preferences. This study was funded by CVS Caremark through an unrestricted research grant to Brigham and Women's Hospital. Shrank and Matlin were employees of, and shareholders in, CVS Health at the time of the study; they report no financial interests in products or services that are related to the subject of this study. Spettell is an employee of, and shareholder in, Aetna. Chitnis serves on clinical trial advisory boards for Novartis and Genzyme-Sanofi; has consulted for Bayer, Biogen Idec, Celgene, Novartis, Merck-Serono, and Genentech-Roche; and has received research support from NIH, National Multiple Sclerosis Society, Peabody Foundation, Consortium for MS Centers, Guthy Jackson Charitable Foundation, EMD-Serono, Novartis Biogen, and Verily. Desai reports receiving a research grant from Merck for unrelated work. Gagne is principal investigator of a research grant from Novartis Pharmaceuticals Corporation to the Brigham and Women's Hospital and has received grant support from Eli Lilly, all for unrelated work. He is also a consultant to Aetion and Optum. Minden reports grants from Biogen and other fees from Genentech, EMD Serano, Avanir, and Novartis, unrelated to this study. The other authors have no conflicts to report. This study was presented as a poster at the International Society for Pharmacoepidemiology 32nd Annual Meeting; August 25-28, 2016; Dublin, Ireland.

Outcomes and treatment management of a French cohort suffering from multiple sclerosis: A retrospective epidemiological study

BackgroundDespite a recent interest in Real World Data, such studies are scarce in multiple sclerosis (MS) disease. The objective was to describe the patients, disease progression and use of DMDs in France and compare clinical effectiveness of first-line injectable DMDs. MethodsWe conducted a retrospective multicenter study in France, using data collected by 11 expert centers with the EDMUS software. ResultsOverall, 15,039 French MS patients were followed for a mean of 11.5 years. Mean age at start of disease was 32 years and 74% were women. After the disease onset, median time to reach EDSS 3 was 11 years and 51.8% of patients were relapse-free 2 years after the disease's onset. The mean delay between onset of disease and initiation of treatment was 5.7 ± 6.9 years. Over time, it decreased from 8.8 ± 7.8 to 0.7 ± 0.7 years for initiation of treatment before 2000 vs. after 2010, respectively. Two years after the initiation of treatment, the persistence rate of injectable disease modifying drugs (DMDs) was 60.7%. The effectiveness of these drugs were quite similar. ConclusionThis study brings new insight on the natural history of MS and the use and effectiveness of injectable DMDs in this condition.

First-line disease-modifying drugs in relapsing–remitting multiple sclerosis: an Italian real-life multicenter study on persistence

Objective: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for relapsing–remitting multiple sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. The aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation.Methods: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between 1 January 2015 and 31 July 2016 were enrolled and followed up for at least 12 months or until the drug was discontinued.Results: Of the 520 included patients, 262 (49.6%) started an injectable and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (n = 62, 24%) or on injectable (n = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline Expanded Disability Status Scale (EDSS) scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences.Conclusion: The route of administration alone (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS.

Cladribine tablets : Oral immunotherapy of relapsing-remitting multiple sclerosis with short yearly treatment periods

The selective modulation of lymphocyte numbers and function is an attractive concept in the treatment of relapsing-remitting multiple sclerosis (RMS). Cladribine tablets (Mavenclad®), an oral RMS medication with an innovative treatment concept, have been available since August 2017. This review article summarizes the currently available clinical study data on cladribine tablets and aspects of their use in clinical practice. Cladribine tablets are administered during two treatment phases of 8-10 (two times 4-5) days with a1-year interval. The drug selectively reduces the number of Tand Blymphocytes, which are subsequently gradually reconstituted with divergent kinetics. Apronounced and sustained effect on the clinical and paraclinical MS disease activity is achieved with good tolerability and afavorable overall safety profile. After completing the two short treatment phases, arelevant proportion of the treated patients experience aprolonged treatment-free period with absence of relevant disease activity. Regular monitoring of lymphocyte counts and reliable contraception during the required time frames are the most important safety measures. There is no evidence of an increased risk of malignancies. Cladribine tablets are an important addition to the therapeutic landscape in RMS. With patient-friendly short dosing periods and afavorable adverse event profile, cladribine tablets provide asustained and strong reduction of MS disease activity. The primary target population for cladribine tablets is patients with relevant MS disease activity (highly active RMS) while on first-line treatment, e. g. with injectable disease-modifying drugs.

Perspectives and experiences of Dutch multiple sclerosis patients and multiple sclerosis-specialized neurologists on injectable disease-modifying treatment.

BackgroundThe adherence to treatment with injectable disease-modifying drugs (DMDs) in multiple sclerosis (MS) may benefit from adequate information provision and management of expectations. The communication between patients and physicians is very important in this respect. The current study investigated the perspectives and experiences of the MS patients and neurologists concerning the choice and course of treatment with DMDs in the Netherlands.MethodsThe MS patients (aged 18–60 years; diagnosed with MS at least a year ago, currently treated with injectable DMD treatment) and MS-specialized neurologists (practicing for ≥3 years, treating ≥15 MS patients/month on average, and spending >60% of their time in clinical practice) were asked to complete semistructured Internet-based questionnaires. The neurologists in this study were not necessarily the treating neurologists of the participating MS patients.ResultsIn all, 107 MS patients and 18 MS-specialized neurologists completed the questionnaires. The MS-specialized neurologists in this study reported discussing most of the suggested treatment goals with their patients. The MS patients indicated that certain important treatment goals, ie, reduction in disease progression, reduction or prolongation of time to long-term disability, and reduction in new magnetic resonance imaging lesions, were not discussed with them. More than one-quarter of the patients (27%) would appreciate more information about their treatment. We found evidence for suboptimal patient adherence to MS therapy (23% indicated taking a treatment break) due to diverse side effects, lack of efficacy, or practical issues. As compared to these patient reports, the scale of poor adherence was overestimated by more than half of the neurologists (on average, 30% estimated treatment breaks).ConclusionThe MS patients and MS-specialized neurologists in this study differ in their experiences and perspectives on information provision and adherence to DMDs. Education programs and up-to-date information on MS treatments for both neurologists and patients may be helpful in improving patient involvement and patient–physician communication.

The Swiss Multiple Sclerosis Cohort-Study (SMSC): A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6–12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.

Neurosurgical Approaches in Demyelinating Disorders; Where are We Now?

Demyelinating diseases of the central nervous system (CNS) are a group of autoimmune disorders affecting the myelin sheets of CNS neurons resulting in different neurological deficits and disability. Multiple sclerosis (MS), Devic’s disease, progressive multifocal leukoencephalopathy, acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica (NMO) are among the most common types of demyelinating disorders. Currently MS is the leading cause of neurological disability in young population after trauma . The incidence and prevalence of MS is increasing worldwide primarily due to increase the incidence in female population. Globally, the median estimated incidence of MS is 5.2 (range: 0.5-20.6) per 100,000 p-yrs, the median estimated prevalence of MS is 112.0 (with a range of 5.2-335) per 100,000 p-yrs, and the average disease duration is 20.2 years (range: 7.6-36.2). In Iran, the prevalence and incidence of MS is estimated to be 54.51 and 5.87 per 100,000. Diagnosis of demyelinating disorders is a controversial issue and several criteria has been introduced for the aforementioned subject. Diagnostic criteria for clinically definite MS require documentation of two or more episodes of symptoms and two or more signs that reflect pathology in anatomically noncontiguous white matter tracts of the CNS. The second may be documented by abnormal paraclinical tests such as MRI or evoked potentials (EPs).&#x0D; The standard treatment for patients with demyelinating disorders and especially MS is the medical management. Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis have shown efficacy of new oral disease-modifying drugs, teriflunomide and dimethyl fumarate, with similar or better efficacy than the injectable disease-modifying drugs, IFN-β and glatiramer acetate. In addition, the new oral drugs seem to have a favorable safety profile. Further, the monoclonal antibody alemtuzumab, which in clinical trials has shown superiority to subcutaneous IFN-β 1a, has been approved in Europe. In acute exacerbation and flare up of the disease, methylprednisolone pulse is the only approved treatment.&#x0D; Although the standard of treatment of MS and other demyelinating disorders is medical, but neurosurgical procedures especially the functional neurosurgical interventions has found their way in management of patients with demyelinating disorders. These interventions are used to treat the complications of MS and demyelinating disorders such as tremor, trigeminal neuralgia, movement disorders and neuropathic pains. Most of these interventions are stereotactic in order to obtain precise targeting of a special deep brain nucleus. The first application of deep brain stimulation (DBS) in patients with MS was for treatment of tremor. Recently it has been demonstrated that DBS of ventral intermediate (VIM) nucleus of thalamus results in alleviation of severe, disabling tremor in patients with MS. Other experiments have also demonstrated decreased tremor and improved quality of life in MS patients responsive to DBS.&#x0D; Neuropathic pain and trigeminal neuralgia are among the other complications of demyelinating disorders which are associated with disability and decreased quality of life. Several investigations have shown that DBS of thalamic nuclei would be effective in treatment of neuropathic pain in patients with MS, although the results are controversial and need further investigations. The trigeminal neuralgia is often treated by microsurgical decompression of the trigeminal nerve. However this approach is not effective in patients with demyelinating disorders as they have different pathology. Case series have shown that Gamma Knife surgery (GKS) is an effective and safe treatment for trigeminal neuralgia in patients with MS. No clinical trial is available for comparing the results and outcome between GKS and microsurgical approach. However results of case series are favorable.&#x0D; There are still other field that could be approached surgically in patients with demyelinating disorders. Recent bodies of evidence have demonstrated a link between cervical cord plaques and discopathy in those with MS which needs further investigation. Tumefactive demyelinating lesions (TDL) are another issues observed in patients with MS which have unknown course and pathology. The link between demyelinating disorders and brain tumors is also another issues which deserves further investigation. To take a long story short, although the role of functional neurosurgical procedures in management of patients with demyelinating disorders especially MS is still limited, but there is optimistic horizons for growing role of neurosurgical procedures in management of different complications of demyelinating disorders refractory to medical therapy.Â

New management algorithms in multiple sclerosis.

Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis have shown efficacy of new oral disease-modifying drugs, teriflunomide and dimethyl fumarate, with similar or better efficacy than the injectable disease-modifying drugs, IFN-β and glatiramer acetate. In addition, the new oral drugs seem to have a favorable safety profile. Further, the monoclonal antibody alemtuzumab, which in clinical trials has shown superiority to subcutaneous IFN-β 1a, has been approved in Europe, but not yet in the United States. In de novo-treated patients, the injectables, IFN-β and glatiramer acetate, will to a great extent be replaced by the new orals, dimethyl fumarate and teriflunomide. However, patients who are stable on an injectable with no or minor side-effects could continue their current therapy. Alemtuzumab should be used as a second-line therapy.

CP-144 Electronic auto-injection device for β-interferon administration in multiple sclerosis patients: a new tool to improve adherence

BackgroundAdherence to injectable disease-modifying drugs becomes an imperative to achieve a reduction in the number of relapses and delay disease symptoms in relapsing-remitting multiple sclerosis patients. From our service, we...

Patient assessment of an electronic device for subcutaneous self-injection of interferon β-1a for multiple sclerosis: an observational study in the UK and Ireland.

BackgroundInjectable disease-modifying drugs (DMDs) reduce the number of relapses and delay disability progression in patients with relapsing–remitting multiple sclerosis (RRMS). Regular self-injection can be stressful and impeded by MS symptoms. Auto-injection devices can simplify self-injection, overcome injection-related issues, and increase treatment satisfaction. This study investigated patient responses to an electronic auto-injection device.MethodsPatients with RRMS (n = 63), aged 18–65 years, naïve to subcutaneous (sc) interferon (IFN) β-1a therapy, were recruited to a Phase IV, observational, open-label, multicenter study (NCT01195870). Patients self-injected sc IFN β-1a using the RebiSmart™ (Merck Serono S.A. – Geneva, Switzerland) electronic auto-injector for 12 weeks, including an initial titration period if recommended by the prescribing physician. In week 12, patients completed a questionnaire comprising of a visual analog scale (VAS) to rate how much they liked using the device, a four-point response question on ease of use (‘very difficult’, ‘difficult’, ‘easy’, or ‘very easy’), and a list of ten device functions to rank, based upon their experiences.ResultsSix patients (9.5%) discontinued the study: one switched to manual injection; two discontinued all treatment; three changed therapy. In total, 59 out of 63 patients (93.7%) completed the VAS; 54 out of 59 (91.5%; 95% confidence interval: 81.3%–97.2%) ‘liked’ using the electronic auto-injector (score ≥6), whereas 57 out of 59 (96.6%) rated the device overall as ‘easy’ or ‘very easy’ to use. Device features rated as most useful were the hidden needle (mean [standard deviation] score: 3.3 [3.01]; n = 56), confirmation sound (3.9 [2.45]), and multidose cartridge (4.6 [2.32]). The least useful functions were the dose history list (8.0 [2.57]) and dose history calendar (7.5 [2.30]).ConclusionsThese findings suggest that the electronic auto-injector may be suitable for patients who are new to injectable DMD therapy. Devices that simplify the injection process may help to ensure that patients receive the full benefits of treatment.

Alemtuzumab - A New Efficacy Benchmark in Relapsing-Remitting Multiple Sclerosis?

The disease-modifying drugs (DMDs) available for the treatment of multiple sclerosis (MS) have been used effectively for nearly two decades. These treatments delay the neurorodegenerative process, but do not restore lost neurological function. New oral DMDs are becoming available that offer improved convenience over existing injectable DMDs. Recently, several monoclonal antibody treatments have been developed for MS; the furthest developed is alemtuzumab (Campath-1H). In a landmark phase II clinical trial (CAMMS223) on patients with relapsing–remitting MS (RRMS), short cycles of alemtuzumab given at the start, at 12 months and optionally at 24 months, demonstrated superior and sustained efficacy in terms of relapse rates and magnetic resonance imaging (MRI) findings over the comparator compound, interferon beta-1a (IFNβ-1a), which was given subcutaneously and continuously. Most notably, the mean disability score for patients receiving alemtuzumab showed an unprecedented improvement, whereas for IFNβ-1a it deteriorated. Alemtuzumab in treating RRMS is the subject of two ongoing phase III trials, the results of which have the potential to change future treatments and prognoses for many patients.

Alemtuzumab—A New Efficacy Benchmark in Relapsing–Remitting Multiple Sclerosis?

The disease-modifying drugs (DMDs) available for the treatment of multiple sclerosis (MS) have been used effectively for nearly two decades. These treatments delay the neurorodegenerative process, but do not restore lost neurological function. New oral DMDs are becoming available that offer improved convenience over existing injectable DMDs. Recently, several monoclonal antibody treatments have been developed for MS; the furthest developed is alemtuzumab (Campath-1H). In a landmark phase II clinical trial (CAMMS223) on patients with relapsing–remitting MS (RRMS), short cycles of alemtuzumab given at baseline, at 12 months, and optionally at 24 months, demonstrated superior and sustained efficacy in terms of relapse rates and magnetic resonance imaging (MRI) findings over the comparator compound, interferon beta-1a (IFNβ-1a), which was given subcutaneously and continuously. Most notably, the mean disability score for patients receiving alemtuzumab showed an unprecedented improvement, whereas for IFNβ-1a it deteriorated. Alemtuzumab in treating RRMS is the subject of two ongoing phase III trials, the results of which have the potential to change future treatments and prognoses for many patients.

Addressing the need for increased adherence to multiple sclerosis therapy: can delivery technology enhance patient motivation?

Background: Several injectable disease-modifying drugs are available for the treatment of multiple sclerosis (MS) to control disease progression and reduce relapse frequency and severity. However, the benefits offered by treatment may be compromised by suboptimal levels of adherence to prescribed regimens. Objective: To examine what is now known about adherence to MS therapies, and to discuss how technological advances may affect adherence in the future, with reference to examples from other therapy areas. Results: Perceived lack of efficacy and therapy-related adverse events are important factors influencing poor adherence. Comprehensive patient education and support are vital in maintaining adherence to MS therapies. Also, improvements in the tolerability, convenience of administration and patient acceptability of MS therapies may enhance adherence. This may be achieved by adjustments to drug formulation and the use of injection devices. Auto-injector devices have been shown to reduce the incidence of injection-site reactions and discomfort in patients with MS, and it is hoped that improvements in delivery technology may further enhance patient motivation to remain adherent to MS therapy in the future. The most recent advance in injection-delivery technology is the development of electronic devices, which can be adjusted for comfort and record dosing history. Conclusions: Few studies have directly addressed adherence to MS therapy and further clarification is required. Adjustments to drug formulation, provision of patient education and improvements to injection devices may all contribute indirectly to improved adherence in the future.