Possible Influence of the Route of Treatment Administration on Treatment Adherence in Patients With Multiple Sclerosis

Sánchez-Martinez, I; Sánchez, María del Carmen Romero; Román, Javier López; Martinez, F; Carreón-Guarnizo, Ester; Lallana, Jose-Eustasio Meca; Rentero, Pilar Zafrilla

doi:10.1016/j.clinthera.2020.03.005

Cited by 12 publications

(4 citation statements)

References 31 publications

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“…This finding is consistent with another Spanish study that reported higher scores in the adherent group for each of the four dimensions of the MSQOL-54 questionnaire for injectable treatments and oral treatments. 29 Our results are also in line with other studies 6,30 which indicate that cognitive impairment is significantly associated with non-adherence. One of the possible consequences of cognitive impairment for adherence is the increase in forgetfulness.…”

Section: Discussionsupporting

confidence: 92%

Factors Associated with Therapeutic Adherence in Multiple Sclerosis in Spain

Soria¹,

Prieto²,

Lázaro³

et al. 2023

PPA

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Adherence to disease-modifying therapies (DMTs) in multiple sclerosis (MS) is a complex and multidimensional phenomenon. Identifying the predictors of therapeutic adherence in MS will guide the design of interventions to improve health outcomes. Our aim was to assess the degree of adherence to pharmacological treatments, assess the relationship between patientrelated factors and pharmacological adherence and to identify predictors of adherence to pharmacological treatments in patients with MS in Spain. Patients and Methods:A cross-sectional nationwide study was carried out in Spain between December 2020 and September 2021. The web-based evaluation protocol consisted of a self-questionnaire survey designed ad hoc and the application of validated questionnaires to assess adherence, as well as beliefs about medication and quality of life. Predictor variables of adherence to MS treatment were assessed using multivariate analysis. Results: A total of 152 patients with MS participated (mean age: 44 years; 64% were female; and 78% had relapsing-remitting MS). Seventy-three percent of the patients reported being adherent to their pharmacological treatment for MS. Forgetfulness was the most common cause of non-adherence. Necessity beliefs and concerns beliefs were not statistically associated with adherence. The adherent group shows statistically significant better levels of quality of life in the cognitive function subscale than the non-adherent participants (p=0.040). Role limitations-emotional, emotional well-being and overall quality of life were not significantly associated with adherence. Predictors with a statistical association with adherence to treatment were years of education (OR=0.79; 95% CI: 0.65-0.96; p=0.020) and intravenous treatment (OR=3.17; 95% CI: 1.07-9.45; p=0.038). Conclusion:We found an adequate adherence to pharmacological treatment. Low education and intravenous treatment were significant predictors of adherence to DMTs.

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Section: Discussionsupporting

confidence: 92%

Factors Associated with Therapeutic Adherence in Multiple Sclerosis in Spain

Soria¹,

Prieto²,

Lázaro³

et al. 2023

PPA

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“…A few studies have compared adherence between oral DMDs and injectable DMDs. A recent study by Martinez et al reported that a change in the route of administration from injectable to oral was associated with increased adherence ( 49 ). Two retrospective analyses of short-term claims data in the US observed higher adherence to the treatment in patients initiating an oral DMD (fingolimod) compared to those initiating injectable DMDs ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 99%

Adherence to subcutaneous interferon beta-1a treatment among patients with relapsing multiple sclerosis: the MAIN-MS study

Al-Roughani,

Zakaria,

Cupler

et al. 2023

Front. Neurol.

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Introduction and backgroundAdherence is a critical factor for optimal clinical outcomes in multiple sclerosis (MS) treatment. This study investigated the adherence and clinical outcomes of MS patients treated with subcutaneous (sc) interferon (IFN) (β)-1a, an established immunomodulatory treatment for relapsing MS. The benefits of a patient support programme (PSP) were also studied.MethodsThis phase-IV prospective, observational multicentre study enrolled patients with relapsing MS who were treated with sc IFN β-1a for 24 months was conducted at 53 centres across 17 countries. The primary endpoint was adherence to sc IFN β-1a treatment, as assessed using Morisky Green Levine Medication Adherence Scale (MGLS) scores at 24 months. The MGLS is a self-reported diagnostic tool to address medication non-adherence, with a score ranging from 0 to 4, with 0 representing high adherence, 1–2 representing medium adherence, and 3–4 representing low adherence. Other endpoints included time to study and treatment discontinuation over 24 months, the proportion of relapse-free patients, and Expanded Disability Status Scale (EDSS) progression (defined as ≥1.0 point increase sustained for 3 months) at 24 months. A subgroup analysis was performed for endpoints based on patients assigned to PSP (yes/no—PSP versus non-PSP subgroup).ResultsOf the 577 patients enrolled, 408 had evaluable MGLS scores at 24 months. A total of 336 (58.2%; 95% confidence interval [CI]: 54.1–62.3%) patients reported high adherence, 57 (9.9%; 95% CIs: 7.6–12.7%) reported medium adherence, and 15 (2.6%; 95% CI: 1.5–4.3%) reported low adherence at 24 months. The PSP subgroup reported higher adherence (n = 206; 65.8%) than the non-PSP subgroup (n = 130; 56.5%). By 24 months, 52.2% of the patients were relapse-free and 17.2% patients experienced ≥1 relapse. Expanded Disability Status Scale progression was observed in 12.3% of patients. Over the 24-month period, 30.8% of the patients discontinued treatment, and the most common reasons for treatment discontinuation were adverse events (AEs, 10.4%), being lost to followup (7.1%), and a lack of efficacy (5.5%). Overall, 39.6% patients experienced ≥1 AE, which ranged from mild to moderate.ConclusionThe study demonstrated high adherence to sc IFN β-1a treatment with an added benefit of PSP participation. More than half of the patients remained relapse-free over a 24-month period. No new safety concerns to sc IFN β-1a treatment were observed.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT02921035, NCT02921035.

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“…Nevertheless, there are still drawbacks on the development of antibodies as drugs, including not only their high cost of manufacture due to their complexity or the low drug survival in long-term treatments (only shown for secukinumab, but not for ixekizumab or brodalumab) but also their lack of oral bioavailability, the preferred administration route for patients, who are generally reluctant to use injectables [25,26]. Therefore, oral administration may improve the adherence and patient satisfaction with their chronic treatments [40]. Dosing regimen is another point to consider, since biologics do not need to be taken daily in psoriasis management, while optimal administration of small molecules would be defined by ADME, pharmacokinetics/pharmacodynamics and half-life time data to improve the effectiveness of treatment by maximizing drug efficacy and minimize toxicity.…”

Section: Discussionmentioning

confidence: 99%

Discovery of novel immunopharmacological ligands targeting the IL-17 inflammatory pathway

Álvarez-Coiradas

Munteanu

Diaz-Saez

et al. 2020

International Immunopharmacology

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Interleukin 17 (IL-17) is a proinflammatory cytokine that acts as an immune checkpoint for several autoimmune diseases. Therapeutic neutralizing antibodies that target this cytokine have demonstrated clinical efficacy in psoriasis. However, biologics have limitations such as their high cost and their lack of oral bioavailability. Thus, it is necessary to expand the therapeutic options for this IL-17A/IL-17RA pathway, applying novel drug discovery methods to find effective small molecules. In this work, we combined biophysical and cell-based assays with structure-based docking to find novel ligands that target this pathway. First, a virtual screening of our chemical library of 60 000 compounds was used to identify 67 potential ligands of IL-17A and IL-17RA. We developed a biophysical label-free binding assay to determine interactions with the extracellular domain of IL-17RA. Two molecules (CBG040591 and CBG060392) with quinazolinone and pyrrolidinedione chemical scaffolds, respectively, were confirmed as ligands of IL-17RA with micromolar affinity. The anti-inflammatory activity of these ligands as cytokinerelease inhibitors was evaluated in human keratinocytes. Both ligands inhibited the release of chemokines mediated by IL-17A, with an IC50 of 20.9 ± 12.6 μM and 23.6 ± 11.8 μM for CCL20 and an IC50 of 26.7 ± 13.1 μM and 45.3 ± 13.0 μM for CXCL8. Hence, they blocked IL-17A proinflammatory activity, which is consistent with the inhibition of the signalling of the IL-17A receptor by ligand CBG060392. Therefore, we identified two novel immunopharmacological ligands targeting the IL-17A/IL-17RA pathway with antiinflammatory efficacy that can be promising tools for a drug discovery program for psoriasis.

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Possible Influence of the Route of Treatment Administration on Treatment Adherence in Patients With Multiple Sclerosis

Cited by 12 publications

References 31 publications

Factors Associated with Therapeutic Adherence in Multiple Sclerosis in Spain

Factors Associated with Therapeutic Adherence in Multiple Sclerosis in Spain

Adherence to subcutaneous interferon beta-1a treatment among patients with relapsing multiple sclerosis: the MAIN-MS study

Discovery of novel immunopharmacological ligands targeting the IL-17 inflammatory pathway

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