Comparative Adherence Trajectories of Oral Fingolimod and Injectable Disease Modifying Agents in Multiple Sclerosis

Figures & data

Table 1 Characteristics of Oral and Injectable DMA Users with MS and the Standard Differences of Covariates Between Both Groups Before and After IPTW Weighting: IBM MarketScan 2010–2012

Characteristic	Route of Administration		Total (N=1,700; 100.00%)	p-value	Standard Difference Before IPTW	Standard Difference After IPTW
	Oral Fingolimod Users (N=269; 15.8%)	Injectable DMA Users (N=1,431; 84.2%)
	N (%)	N (%)	N (%)
Predisposing variables
Age (in years, Mean ± SD)	45.6 ± 10.0	43.2 ± 10.8	43.6 ± 10.7	0.114
Age Group (in years)				0.001	−0.26	0.01
18–44	109 (40.5%)	761 (53.2%)	870 (51.2%)
45–64	160 (59.5%)	670 (46.8%)	830 (48.8%)
Gender				0.808	−0.02	−0.04
Male	55 (20.4%)	302 (21.1%)	357 (21.0%)
Female	214 (79.6%)	1,129 (78.9%)	1,343 (79.0%)
Region				0.160
Northeast	37 (13.8%)	260 (18.2%)	297 (17.5%)
North central	64 (23.8%)	273 (19.1%)	337 (19.8%)
South	99 (36.8%)	541 (37.8%)	640 (37.6%)
West	69 (25.6%)	357 (24.9%)	426 (25.1%)
Region				0.926	0.01	−0.15
Northeast/North central	101 (37.6%)	533 (37.3%)	634 (37.3%)
South/West	168 (62.5%)	898 (62.7%)	1,066 (62.7%)
Enabling Variables
Employment Status				0.029	−0.16	0.00
Active Full Time	203 (75.5%)	1,173 (82.0%)	1,376 (80.9%)
Others*	66 (24.5%)	258 (18.0%)	324 (19.1%)
Plan Indicator				0.725	−0.02	0.10
Others (HMO, POS, EPO, POS with capitation, CDHP, HDHP)	108 (40.2%)	591 (41.3%)	699 (41.1%)
Preferred Provider Organization (PPO)	161 (59.8%)	840 (58.7%)	1,001 (58.9%)
Physician Specialty Coding Flag				0.921
<70% of outpatient physician records have specialty indicated	10 (3.7%)	55 (3.8%)	65 (3.8%)
70% or more of outpatient physician records have specialty indicated	259 (96.3%)	1,376 (96.2%)	1,635 (96.2%)
Date Year Incurred				<0.050	−0.40	−0.04
2010	22 (8.2%)	321 (22.4%)	343 (20.2%)
2011	247 (91.8%)	1,110 (77.6%)	1,357 (79.8%)
Need Factors
Mean Elixhauser Score [Mean ± SD]	1.8 ± 4.1	2.0 ± 4.1	2.0 ± 4.1	0.013
Selected AHRQ CCS comorbidities that are prevalent in MS Patients
Infections	68 (25.3%)	281 (19.6%)	349 (20.5%)	0.036	−0.14	0.06
Cancer	46 (17.1%)	185 (12.9%)	231 (13.6%)	0.067	−0.12	0.03
Metabolic Disorders
Thyroid Disorders	28 (10.4%)	136 (9.5%)	164 (9.7%)	0.645	−0.03	0.03
Diabetes Mellitus	21 (7.8%)	130 (9.1%)	151 (8.9%)	0.499	0.05	0.09
Nutritional Deficiencies	15 (5.6%)	128 (8.9%)	143 (8.4%)	0.068	0.13	−0.09
Lipid Disorders	33 (12.3%)	197 (13.8%)	230 (13.5%)	0.510	0.04	0.10
Mental Illness
Anxiety	12 (4.5%)	94 (6.6%)	106 (6.2%)	0.190	0.09	−0.07
Bipolar Disorders	7 (2.6%)	28 (2.0%)	35 (2.1%)	0.494	−0.04	0.02
Depression	33 (12.3%)	138 (9.6%)	171 (10.1%)	0.189	−0.08	0.11
Neurological Disorders
Paralysis	15 (5.6%)	54 (3.8%)	69 (4.1%)	0.169	−0.09	0.06
Epilepsy	4 (1.5%)	20 (1.4%)	24 (1.4%)	0.909	−0.01	0.06
Convulsions	5 (1.9%)	35 (2.5%)	40 (2.4%)	0.560	0.04	0.04
Migraine headache	12 (4.5%)	127 (8.9%)	139 (8.2%)	0.015	0.18	0.01
Other Headaches	25 (9.3%)	229 (16.0%)	254 (14.9%)	0.005	0.20	0.14
Eye Disorders	121 (45.0%)	393 (27.5%)	514 (30.2%)	<0.050	−0.37	0.05
Ear Disorders	22 (8.2%)	206 (14.4%)	228 (13.4%)	0.006	0.20	−0.09
Other Neurological Disorders†	102 (37.9%)	786 (54.9%)	888 (52.2%)	<0.050	0.35	0.14
Circulatory/Vascular Disorders
Hypertension	38 (14.1%)	219 (15.3%)	257 (15.1%)	0.621	0.03	0.11
Heart Diseases	62 (23.1%)	208 (14.5%)	270 (15.9%)	0.001	−0.22	0.10
Cerebrovascular Disease	12 (4.5%)	155 (10.8%)	167 (9.8%)	0.001	0.24	−0.10
Respiratory Disorders
Chronic Lung Disease (CLD)	8 (3.0%)	24 (1.7%)	32 (1.9%)	0.151	−0.04	0.12
Gastrointestinal Disorders
Liver Diseases	4 (1.49%)	35 (2.5%)	39 (2.3%)	0.335	0.07	−0.03
Genitourinary Disorders
Diseases of the Urinary System	71 (26.4%)	266 (18.6%)	337 (19.8%)	0.003	−0.19	0.11
Complications related to Pregnancy/Childbirth	5 (1.9%)	76 (5.3%)	81 (4.8%)	0.015	0.19	0.11
Diseases of the skin and subcutaneous tissue	53 (19.7%)	175 (12.2%)	228 (13.4%)	0.001	−0.21	0.08
Musculoskeletal Disorders
Non-traumatic joint disorders	51 (19.0%)	252 (17.6%)	303 (17.8%)	0.596	−0.03	0.06
Spondylosis, intervertebral disc disorders, other back problems	83 (30.9%)	557 (38.9%)	640 (37.7%)	0.012	0.17	0.04
Other connective tissue diseases (including Fibromyalgia)	58 (21.6%)	423 (29.6%)	481 (28.3%)	0.008	0.18	0.03
Ill-defined Conditions
Nausea, vomiting/abdominal Pain	26 (9.7%)	162 (11.3%)	188 (11.1%)	0.427	0.05	−0.02
MS related Symptoms/Mobility Impairment	161 (59.9%)	902 (63.0%)	1,063 (62.5%)	0.323
MS related symptoms	703 (58.7%)	896 (62.6%)	1,054 (62.0%)	0.229
Bladder/bowel symptoms	31 (11.5%)	105 (7.3%)	136 (8.0%)	0.020
Brainstem symptoms	23 (8.6%)	222 (15.5%)	245 (14.4%)	0.003
Cerebellar symptoms	34 (12.6%)	192 (13.4%)	226 (13.3%)	0.730
Cerebral symptoms/cognitive Impairment	8 (3.0%)	48 (3.4%)	56 (3.3%)	0.749
Difficulty walking/gait problems	23 (8.6%)	113 (7.9%)	136 (8.0%)	0.717
General symptoms	35 (13.0%)	257 (18.0%)	292 (17.2%)	0.048
Pyramidal symptoms	26 (9.7%)	113 (7.9%)	139 (8.2%)	0.331
Sensory symptoms	2 (0.7%)	27 (1. 9%)	29 (1.7%)	0.184
Speech symptoms	39 (14.5%)	413 (28.9%)	452 (26.6%)	<0.050
Visual symptoms	54 (20.1%)	215 (15.0%)	269 (15.8%)	0.037
Mobility Impairment - Durable Medical Equipment (DME)	17 (6.3%)	55 (3.84%)	72 (4.2%)	0.064
MS Severity Score [MSSS, Mean ± SD]	1.5 ± 1.8	1.6 ± 1.9	1.6 ± 1.9	0.896
MS Symptomatic Medication
Analgesics	209 (77.7%)	1,122 (78.4%)	1,331 (78.3%)	0.795	0.02	−0.10
Anticonvulsants	68 (25.3%)	318 (22.2%)	386 (22.7%)	0.272	−0.05	0.09
Antidepressants	161 (59.9%)	819 (57.2%)	980 (57.7%)	0.425	−0.31	0.13
Bladder Dysfunction Drugs	83 (30.9%)	256 (17.9%)	339 (19.9%)	<0.050	−0.04	0.01
Cognition drugs	7 (2.6%)	39 (2.7%)	46 (2.7%)	0.909	−0.26	0.14
Erectile dysfunction drugs	7 (2.6%)	59 (4.1%)	66 (3.9%)	0.236	−0.42	0.06
Fatigue Drugs	80 (29.7%)	398 (27.8%)	478 (28.1%)	0.519	0.08	−0.04
Impaired walking drugs	65 (24.2%)	129 (9.0%)	194 (11.4%)	<0.050	−0.07	−0.08
Spasticity Drugs	192 (71.4%)	846 (59.1%)	1,038 (61.1%)	0.0001	0.01	0.09
Healthcare Utilization
Relapse	42 (15.6%)	267 (18.7%)	309 (18.2%)	0.235	0.08	0.05
Neurologist consultation	143 (53.2%)	610 (42.6%)	753 (44.3%)	0.001	−0.21	0.00
Magnetic resonance imaging (MRI)	5 (1.9%)	60 (4.2%)	65 (3.8%)	0.067	0.14	0.03
Emergency department (ED) visits				0.025	0.15	0.18
No ED visit	221 (82.2%)	1,086 (75.9%)	1,307 (76.9%)
ED Visit	48 (17.8%)	345 (24.1%)	393 (23.1%)

Notes: * Other employment status include part-time/seasonal, early retiree, long-term disabled, etc. † Other neurological disorders include cerebral degeneration (unspecified), Parkinson’s disease, Huntington’s chorea, other choreas, neuroleptic malignant syndrome, spinocerebellar disease, trigeminal nerve disorders, other retinal disorders, other demyelinating diseases of central nervous system (neuromyelitis optica, Schilder’s disease, acute transverse myelitis, other demyelinating diseases of central nervous system), epilepsy and recurrent seizures, anoxic brain damage, encephalopathy, convulsions and aphasia Standard differences for certain covariates was not shown as they were not considered for propensity score weighting due to multicollinearity.

Abbreviations: MS, multiple sclerosis; DMA, disease modifying agent; IPTW, inverse probability treatment weighting; SD, standard deviation; HMO, health maintenance organization; POS, point-of-service; PPO, preferred provider organization; EPO, exclusive provider organization; CDHP, consumer-directed health plan; HDHP, high deductible health plan.

Figure 1 Flowchart For Study Cohort Derivation: IBM MarketScan 2010–2012.

Figure 2 Adherence Trajectories of Patients with MS who received Oral Fingolimod or Injectable DMAs. Rapid discontinuers: Patients who discontinued DMAs early within 3–4 months after the initiation. Complete adherers: Patients who were almost completely adherent to DMA throughout the follow-up period. Slow decliners: Patients whose adherence gradually declined during the follow-up period.

Abbreviations: MS, multiple sclerosis; DMA, disease modifying agent.

Table 2 Adherence Trajectories Between Oral Fingolimod and Injectable DMA Users in Patients with MS

Adherence Trajectory Group (Mean PDC±SD)	Route of Administration
	Oral Fingolimod N=269 (15.8%)	Injectable DMAs* N=1,431 (81.2%)	Total N=1,700 (100.00%)	p value
1. Rapid discontinuers (0.24±0.13)	31 (11.5%)	368 (25.7%)	399 (23.5%)	<0.001
2. Complete adherers (0.96±0.05)	171 (63.6%)	677 (47.3%)	848 (49.9%)
3. Slow decliners (0.64±0.14)	67 (24.9%)	386 (27.0%)	453 (26.6%)

Note: *Injectable DMAs included interferon beta and glatiramer acetate.

Abbreviations: MS, multiple sclerosis; DMA, disease modifying agent; PDC, proportion of days covered; SD, standard deviation.

Table 3 Findings of IPTW Weighted Multinomial Logistic Regression

Association of DMA Adherence Trajectory with DMA Route of Administration (Reference Trajectory Group: Group 1, Rapid Discontinuers)
DMA Route of Administration	Sample	Adherence Trajectory Group
		Group 2 (Complete Adherers)	Group 3 (Slow Decliners)
		aOR (95% CI)	aOR (95% CI)
Injectable DMAs		Reference	Reference
Oral Fingolimod	Original Sample	2.78 (1.85–4.16)	2.62 (1.70–4.05)

Abbreviations: MS, multiple sclerosis; DMA, disease modifying agent; aOR, adjusted odds ratio; CI, confidence interval; IPTW, inverse probability treatment weights.