Treatment adherence and other patient-reported outcomes as cost determinants in multiple sclerosis: a review of the literature

Figures & data

Figure 1 Flow-chart summary of literature search.

Abbreviations: DMT, disease-modifying therapy; n, number.

Table 1 Characteristics of the studies included in this review

Reference (country)	Study design	Focus of study	Study quality	Objective of study	Population inclusion criteria	Main results
Beer et al^Citation32 (Switzerland)	Observational multicenter study	Compliance/frequency of ISRs	CEBM: 2c (B) IF: 2.167 Citations: 7 (WS), 12 (GS)	To compare the prevalence of ISRs with different formulation of DMTs and their impact on treatment adherence	412 patients between 18–55 years old with RMS or CIS and on DMT for at least 2 years	ISRs were reported by 13.4% of patients on IM IFN β-1a, 57.7% on SC IFN β-1b, 67.9% on SC IFN β-1a, and 30.4% on GA. Primary reasons for discontinuing or switching therapy were ISRs or lack of efficacy
de Seze et al^Citation31 (France)	Cross-sectional observational study	Compliance/patients’ treatment perceptions	CEBM: 2c (B) IF: 1.143 Citations: 3 (WS), 8 (GS)	To determine patient perceptions and awareness of MS and its treatment, treatment adherence, and impact on quality of life and daily living	202 patients with RRMS, EDSS ≤5.5, and DMT prescription for at least 3 months	The most frequently given reason for nonadherence was forgetfulness (38.7%). Adherence was significantly higher in well-informed patients (P=0.035)
Ivanova et al^Citation25 (USA)	Retrospective cohort study	Adherence	CEBM: 3b (B) IF: 0 Citations: 10 (GS)	To examine the difference in direct and indirect costs between DMT-adherent and nonadherent patients	648 company employees aged 18–62 years who had at least one MS diagnosis (ICD-9-CM: 340.x) between January 1999 and December 2007 and at least one DMT pharmacy claim	DMT-adherent patients had a lower rate of severe relapse (12.4% versus 19.9%; P=0.0013) and significant lower mean (SD) all-cause inpatient cost (€648.71 [€3,753.74] versus €1,740.88 [€6,127.27]; P=0.0018) and all-cause ED cost (€147.82 [€430.79] versus €242.42 [€592.96]; P=0.0044) compared with nonadherent patients
Johnson et al^Citation34 (USA)	DCE	DMT preferences	CEBM: 2c (B) IF: 3.578 Citations: 24 (WS), 41 (GS)	To estimate the willingness of MS patients to accept life-threatening adverse-event risks in exchange for improvements in MS-related health outcomes	651 MS patients	Delay in years to disability progression was the most important factor in treatment preferences. In return for decreases in relapses rates (from 4 years to 1 year) and increases in the delay in progression (from 3 years to 5 years), patients were willing to accept a 0.38% annual risk of death or disability from PML, a 0.39% risk from liver failure, and 0.48% risk from leukemia
Menzin et al^Citation20 (USA)	Systematic review	Adherence	CEBM: 3a (B) IF: 2.250 Citations: 4 (WS), 10 (GS)	To evaluate rates of adherence to DMTs in MS and the impact of adherence on both clinical and economic outcomes from the patient and payer perspectives, according to published literature	Studies written in English and published between May 2001 and May 2011 that involved a population of MS patients using DMTs and reporting a measurement of adherence were included. Studies reporting persistence measures or rates of switching between DMTs were excluded	Adherence to DMTs ranged from 41%–88%. Mean adherence rates were higher for IM IFN β-1a (69.4%) and SC IFN β-1b than for SC IFN β-1a or GA. Risk of MS relapses, disease progression, and inpatient or ED utilization was higher among nonadherent patients
Oleen-Burkey et al^Citation26 (USA)	Retrospective cohort study	Adherence	CEBM: 4 (C) IF: 0 Citations: 6 (GS)	To examine how changes in MPR affect the probability of MS relapses and total and MS-related costs among patients treated with GA	839 individuals with a diagnosis code for MS (ICD-9-CM 340.xx) and using GA injection	Patients who achieved an MPR of at least 70% had significantly lower odds of relapse (OR=0.547, 95% CI=0.362–0.826) than those with lower MPR: 50% (OR=0.69, 95% CI=0.461–1.033), 25% (OR=0.832, 95% CI=0.511–1.357) and 1% (OR=0.761, 95% CI=0.366–1.583). Patients with MPRs of at least 50% had €2,665.57 (P=0.002), €851.93 (P=0.004), and €75.89 (P=0.006) lower inpatient, outpatient, and ED costs, respectively, than patients with lower MPRs
Swinburn et al^Citation35 (UK)	DCE	Device preferences	ISPOR 13th Annual International Meeting Abstract (2012)	To estimate the influence of different treatment-related attributes on patients’ choice of DMT device	100 device-using MS patients	Efficacy had the largest effect on treatment selection (OR: 0.117; P≤0.001). Compact, ready-to-use, nonrefrigerated devices that were easily placed on the injection area were strongly favored
Szkurhan et al^Citation28 (Canada and USA)	Decision-analytic model	Persistency	ISPOR 17th Annual European Congress Abstract (2010)	To estimate nonpharmacy medical costs associated with persistence to DMTs in MS patients	NA	Patient annual medical cost for IM IFN β-1a patients was €6,104.89, showing an advantage over patients on IM IFN β-1b (€6,210.94) and SC IFN β-1a (€6,697.89)

Abbreviations: ISR, injection-site reaction; CEBM, Centre for Evidence-Based Medicine (level of evidence); IF, impact factor; WS, Web of Science; GS, Google Scholar; DMT, disease-modifying therapy; RMS, relapsing multiple sclerosis; CIS, clinically isolated syndrome; IM, intramuscular; IFN, interferon; SC, subcutaneous; GA, glatiramer acetate; MS, multiple sclerosis; RRMS, relapsing–remitting multiple sclerosis; EDSS, Expanded Disability Status Scale; ICD-9-CM, International Classification of Diseases, 9th Revision; SD, standard deviation; DCE, discrete choice experiment; PML, progressive multifocal leukoencephalopathy; ED, emergency department; MPR, medication possession ratio; ISPOR, International Society of Pharmacoeconomics and Outcomes Research; OR, odds ratio; NA, not available; CI, confidence interval.

Figure 2 Comparison between the percentage of adherent and nonadherent patients with at least one severe multiple sclerosis relapse, inpatient visit, and emergency department visit over 1 year.

Note: Data from Tan et al²⁴ and Ivanova et al.²⁵
Abbreviations: MS, multiple sclerosis; ED, emergency department.

Table S1 PubMed search terms, strategies, and title identified

Search terms	Title identified
“Multiple sclerosis” AND “adherence” AND “cost”	26
“Multiple sclerosis” AND “compliance” AND “cost”	31
“Multiple sclerosis” AND “persistence” AND “cost”	8
“Multiple sclerosis” AND “route of administration” AND “compliance”	23
“Multiple sclerosis” AND “adherence” AND “device”	13
“Multiple sclerosis” AND “route of administration” AND “adherence”	48
“Multiple sclerosis” AND “device” AND “cost”	18
“Multiple sclerosis” AND “device” AND “compliance”	12
“Multiple sclerosis” AND “route of administration” AND “persistence”	9
“Multiple sclerosis” AND “route of administration” AND “cost of disease”	13
“Multiple sclerosis” AND “route of administration” AND “disease burden”	11
“Multiple sclerosis” AND “treatment satisfaction”	134
“Multiple sclerosis” AND “preferences”	27
“Multiple sclerosis” AND “willingness to pay”	11

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