Adherence to disease-modifying therapies and its impact on relapse, health resource utilization, and costs among patients with multiple sclerosis

Figures & data

Figure 1 Attrition and inclusion of the study sample.^a

Notes: ^aStudy period January 1, 2008, to September 30, 2015; ^bindex date defined as date of first DMT claim.
Abbreviations: DMT, disease-modifying therapy; MS, multiple sclerosis.

Table 1 DMTs for MS included in the retrospective claims database analysisa

Route	DMT	Manufacturer	Dosing frequency	Approval year (US)
Injectable	Avonex^® (IFNβ-1a)	Biogen	Once weekly	1996
	Betaseron^® (IFNβ-1b)	Bayer Healthcare Pharmaceuticals	Every other day	1993
	Copaxone^® (glatiramer acetate 20/40 mg)	Teva Pharmaceuticals	Daily/3 times weekly	1996/2014
	Extavia^® (IFNβ-1b)	Novartis Pharmaceuticals	Every other day	2009
	Rebif^® (IFNβ-1a)	EMD Serono	3 times weekly	2002
	Tysabri^® (natalizumab)	Biogen	Once every 4 weeks	2004
Oral	Aubagio^® (teriflunomide)	Genzyme	Once daily	2012
	Gilenya^® (fingolimod)	Novartis Pharmaceuticals	Once daily	2010
	Tecfidera^® (dimethyl fumarate)	Biogen	Twice daily	2013

Note:

a More recently approved DMTs – including Zinbryta^® (daclizumab), once-weekly injectable; Glatopa^® (glatiramer acetate 20 mg), once-daily injectable; Lemtrada^® (alemtuzumab) daily infusion on five consecutive days the first year and on three consecutive days one year apart from first year and PLEGRIDY^® (PEG-IFNβ-1a), injectable every 14 days – were not included, due to insufficient claims data at the end of the study period (September 30, 2015).

Abbreviations: DMTs, disease-modifying therapies; MS, multiple sclerosis.

Table 2 Baseline demographic and clinical characteristics of study sample (n=12,431)

Variables	Total sample (n=12,431)	Injectable (n=11,413)	Oral (n=1,018)	P-value*
Age at index date, years, mean (SD)	44.55 (10.36)	44.56 (10.35)	44.41 (10.52)	0.3877
Age group, years, n (%)
18–24	414 (3.33)	370 (3.24)	44 (4.32)	0.3791
25–34	1,864 (14.99)	1,720 (15.07)	144 (14.15)
35–44	3,704 (29.8)	3,393 (29.73)	311 (30.55)
45–54	4,036 (32.47)	3,710 (32.51)	326 (32.02)
55–64	2,413 (19.41)	2,220 (19.45)	193 (18.96)
Sex, n (%)
Female	9,478 (76.24)	8,744 (76.61)	734 (72.1)	0.0012
Male	2,953 (23.76)	2,669 (23.39)	284 (27.9)
CCI score, mean (SD)	1.17 (1.53)	1.14 (1.53)	1.42 (1.58)	<0.0001
CCI score, n (%)
0	4,667 (37.54)	4,411 (38.65)	256 (25.15)	<0.0001
1	4,848 (39)	4,392 (38.48)	456 (44.79)
2	1,244 (10.01)	1,110 (9.73)	134 (13.16)
≥3	1,672 (13.45)	1,500 (13.14)	172 (16.9)

Note:

* Statistically significant (P<0.05) differences between injectable and oral DMT cohorts determined by χ² test for categorical variables and Wilcoxon rank-sum test for continuous variables.

Abbreviations: CCI, Charlson Comorbidity Index; SD, standard deviation; DMT, disease-modifying therapy.

Table 3 Differences in adherence, discontinuation, and switches between patients with MS initiating oral and injectable DMTs in the US

Variables	Injectable (n=11,413)	Oral (n=1,018)	P-value*
PDC, mean (SD)	0.7259 (0.2869)	0.7257 (0.2934)	0.0787
PDC group, n (%)
<0.2	864 (7.57)	112 (11)	<0.0001
0.2–<0.4	1,227 (10.75)	80 (7.86)
0.4–<0.6	1,147 (10.05)	69 (6.78)
0.6–<0.8	1,489 (13.05)	132 (12.97)
≥0.8	6,686 (58.58)	625 (61.39)
PDC category, n (%)
<0.8 (non-adherent)	4,727 (41.42)	393 (38.61)	0.0806
≥0.8 (adherent)	6,686 (58.58)	625 (61.39)
DMT discontinuation
n (%)	2,089 (18.3)	172 (16.9)	0.2645
Days on therapy, mean (SD)	123.69 (75.61)	110.30 (78.85)	0.0039
DMT switch
n (%)	1,156 (13.63)	121 (11.89)	0.1178
Days on therapy, mean (SD)	166.00 (101.77)	122.80 (96.77)	<0.0001

Note:

* Statistically significant (P<0.05) difference determined by χ² test for categorical variables and Wilcoxon rank-sum test for continuous variables.

Abbreviations: MS, multiple sclerosis; DMTs, disease-modifying therapies; PDC, proportion of days covered; SD, standard deviation.

Table 4 Logistic regression analysis: predictors of adherence to index DMT (PDC ≥0.8)

Covariates	OR (95% CI)	P-value*
Injectable DMT	Reference
Oral DMT	0.901 (0.789–1.029)	0.1254
Sex
Male	Reference
Female	0.755 (0.693–0.822)	<0.0001
Age at index DMT	1.015 (1.011–1.018)	<0.0001
CCI score
0	Reference
1	1.095 (1.009–1.189)	0.0305
2	0.908 (0.8–1.031)	0.1369
≥3	1.059 (0.944–1.189)	0.3252

Note:

* Statistically significant difference defined as P<0.05.

Abbreviations: DMT, disease-modifying therapy; PDC, proportion of days covered; OR, odds ratio; CI, confidence interval; CCI, Charlson Comorbidity Index.

Table 5 Logistic regression analysis: predictors of MS relapse

Covariates	OR (95% CI)	P-value*
Sex
Male	Reference
Female	1.06 (0.952–1.18)	0.2884
Age at index DMT	0.994 (0.99–0.999)	0.0129
CCI score 0
0	Reference
1	1.351 (1.215–1.51)	<0.0001
2	1.524 (1.305–1.78)	<0.0001
≥3	1.585 (1.378–1.824)	<0.0001
PDC group
<0.8	Reference
≥0.8	0.576 (0.526–0.63)	<0.0001

Note:

* Statistically significant difference defined as P<0.05

Abbreviations: MS, multiple sclerosis; OR, odds ratio; CI, confidence interval; DMT, disease-modifying therapy; CCI, Charlson Comorbidity Index; PDC, proportion of days covered.

Table 6 Predictors of MS-related hospital visits, ER visits, and outpatient visits in patients with MS treated with DMTs (n=12,431)

Variables	Hospital visitsa	P-value	ER visitsa	P-value	Outpatient visitsb	P-value
Sex
Female	Reference		Reference		Reference
Male	0.939 (0.799–1.104)	0.4478	0.826 (0.737–0.925)	0.0009	–0.019 (0.152)	0.901
Age at index DMT	1.029 (1.022–1.036)	<0.0001	0.992 (0.988–0.997)	0.0009	0.01 (0.006)	0.110
CCI score
0	Reference		Reference		Reference
1	1.239 (1.053–1.457)	0.0097	1.457 (1.304–1.628)	<0.0001	1.035 (0.148)	<0.0001
2	1.767 (1.421–2.198)	<0.0001	1.81 (1.545–2.12)	<0.0001	0.94 (0.229)	<0.0001
≥3	1.678 (1.374–2.048)	<0.0001	2.052 (1.782–2.364)	<0.0001	1.724 (0.206)	<0.0001
PDC group
<0.8	Reference		Reference		Reference
≥0.8	0.478 (0.417–0.547)	<0.0001	0.62 (0.565–0.681)	<0.0001	–0.712 (0.132)	<0.0001

Notes:

a Values represent point estimates for the OR (95% CI) generated by logistic regression;

b values represent coefficient estimates (SE) generated by ordinal least-squares regression.

Abbreviations: MS, multiple sclerosis; ER, emergency room; DMTs, disease-modifying therapies; CCI, Charlson Comorbidity Index; PDC, proportion of days covered; OR, odds ratio; CI, confidence interval; SE, standard error.

Figure 2 Predicted mean non-drug medical costs for MS patients adherent (PDC ≥0.8) and non-adherent (PDC <0.8) to index DMT (total n=12,431).

Notes: Predicted mean costs were generated by generalized linear regression and based on the study sample of 5,120 non-adherent patients (PDC <0.8) and 7,311 adherent patients (PDC ≥0.8).
Abbreviations: MS, multiple sclerosis; PDC, proportion of days covered; DMT, disease-modifying therapy; ER, emergency room.

Table 7 Generalized linear regression analysis: predictors of non-drug medical costs in patients with MS on DMT (total n=12,431)a

Variables	Hospitalization costs		ER costs		Outpatient visit costs		Total medical costs
	Parameter	P-value	Parameter	P-value	Parameter	P-value	Parameter	P-value
Sex (male)	−0.081 (0.062)	NS	−0.222 (0.051)	<0.0001	−0.074 (0.036)	0.038	−0.083 (0.037)	0.025
Age at index DMT	0.043 (0.002)	<0.0001	−0.008 (0.002)	<0.0001	0.009 (0.002)	<0.0001	0.015 (0.002)	<0.0001
CCI score
1	0.496 (0.06)	<0.0001	0.423 (0.049)	<0.0001	0.350 (0.035)	<0.0001	0.373 (0.036)	<0.0001
2	0.573 (0.095)	<0.0001	0.651 (0.077)	<0.0001	0.396 (0.054)	<0.0001	0.442 (0.056)	<0.0001
≥3	1.012 (0.083)	<0.0001	0.69 (0.069)	<0.0001	0.59 (0.048)	<0.0001	0.663 (0.05)	<0.0001
PDC group (≥0.8)	−0.942 (0.054)	<0.0001	−0.616 (0.044)	<0.0001	−0.415 (0.031)	<0.0001	−0.564 (0.032)	<0.0001

Note:

a Parameter values for generalized linear regression analyses represent maximum-likelihood estimates (SE).

Abbreviations: MS, multiple sclerosis; DMT, disease-modifying therapy; ER, emergency room; NS, not significant; CCI, Charlson Comorbidity Index; PDC, proportion of days covered; SE, standard error.