Comparison of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis

Comparison of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of Healthcare Resource Utilization and Relapse Rates from US Insurance Claims Data

Jacqueline Nicholas1·Aaron Boster1·Ning Wu2·Wei-Shi Yeh2·Monica Fay2·Jon Kendter2·MingYiHuang2·Andrew Lee2

* Andrew Lee

1 OhioHealth Multiple Sclerosis Center, Riverside Methodist Hospital, Columbus, OH, USA

2 Biogen, 225 Binney Street, Cambridge, MA 02142, USA

Online Resource

Table S1 Poisson regression on ARR for 1 year after initiation of DMT for patients with MS with no DMT exposure in the year before DMT initiation

Explanatory variables / Categories / IRR / 95% CI lower limit / 95% CI upper limit / p-value
Index DMT (ref: dimethyl fumarate)
Interferon β / 1.230 / 1.060 / 1.427 / 0.0064
Glatiramer acetate / 1.268 / 1.102 / 1.459 / 0.0009
Teriflunomide / 1.277 / 1.002 / 1.627 / 0.0479
Fingolimod / 1.071 / 0.853 / 1.345 / 0.5555
Female sex / 1.332 / 1.154 / 1.536 / 0.0001
Age (ref: 18–30 years)
31–40 years / 0.815 / 0.673 / 0.988 / 0.0373
41–50 years / 0.809 / 0.672 / 0.974 / 0.0251
>50 years / 0.821 / 0.678 / 0.994 / 0.043
Region of residence (ref: West)
Northeast / 1.228 / 1.026 / 1.470 / 0.0249
Midwest / 1.085 / 0.901 / 1.306 / 0.3885
South / 1.182 / 0.995 / 1.405 / 0.0568
Unknown / 1.015 / 0.577 / 1.784 / 0.9589
Charlson Comorbidity Index / 1.037 / 0.995 / 1.082 / 0.087
Relapse in prior year (ref: 0)
1 relapse / 2.414 / 2.136 / 2.728 / 0.0001
2 relapses / 4.488 / 3.698 / 5.448 / 0.0001
≥3 relapses / 8.818 / 7.121 / 10.919 / 0.0001
MS-related symptoms
Other causes of myelitis / 1.175 / 0.877 / 1.574 / 0.2802
Demyelinating disease of CNS, unspecified / 1.020 / 0.882 / 1.178 / 0.7935
Disorders of optic nerve and visual pathways / 0.995 / 0.848 / 1.168 / 0.952
Neurogenic bladder NOS / 1.007 / 0.779 / 1.302 / 0.9596
Other disorders of soft tissues: neuralgia, neuritis and radiculitis, unspecified / 1.097 / 0.821 / 1.466 / 0.5327
General symptoms: dizziness and giddiness / 1.016 / 0.867 / 1.191 / 0.8409
General symptoms: fatigue/malaise / 1.159 / 1.030 / 1.304 / 0.0146

Bold indicates significance

ARR annualized relapse rate, CI confidence interval, CNS central nervous system, DMT disease-modifying therapy, IRR incidence rate ratio, MS multiple sclerosis, NOS not otherwise specified

Model parameters for difference-in-difference (DiD) regression analysis changes in total non-prescription medical costs during the 1 year prior to and the 1 year following the index date between cohorts

e_totalDiD.Group:pre_othDMTeq0Modelspec:link=identitydist=normal
TheGENMODProcedure
Model Information
/
Data Set / WORK.ALL2
Distribution / Normal
Link Function / Identity
Dependent Variable / e_total
Number of Observations Read
/ 8388
/
Number of Observations Used / 8388
Criteria For Assessing Goodness Of Fit
/
Criterion
/ DF
/ Value
/ Value/DF
/
Deviance / 8378 / 9.8932856E12 / 1180864840.4
Scaled Deviance / 8378 / 8388.0000 / 1.0012
Pearson Chi-Square / 8378 / 9.8932856E12 / 1180864840.4
Scaled Pearson X2 / 8378 / 8388.0000 / 1.0012
Log Likelihood / -99507.6706
Full Log Likelihood / -99507.6706
AIC (smaller is better) / 199037.3413
AICC (smaller is better) / 199037.3728
BIC (smaller is better) / 199114.7214
Analysis Of Maximum Likelihood Parameter Estimates
/
Parameter
/ DF
/ Estimate
/ Standard
Error
/ Wald 95% Confidence Limits
/ Wald Chi-Square
/ PrChiSq
/
Intercept / 1 / 41271.46 / 638.3984 / 40020.22 / 42522.70 / 4179.42 / <.0001
cohort / AUBAGIO / 1 / 611.4136 / 1740.278 / -2799.47 / 4022.296 / 0.12 / 0.7253
cohort / COPAXONE / 1 / -795.641 / 936.9261 / -2631.98 / 1040.700 / 0.72 / 0.3958
cohort / GILENYA / 1 / 7029.604 / 1542.689 / 4005.990 / 10053.22 / 20.76 / <.0001
cohort / INTERFERON / 1 / -1709.74 / 1008.041 / -3685.46 / 265.9855 / 2.88 / 0.0899
time_period / 1 / 1 / 20459.75 / 638.3984 / 19208.51 / 21710.99 / 1027.11 / <.0001
cohort*time_period / AUBAGIO / 1 / 1 / 627.7477 / 1740.278 / -2783.13 / 4038.630 / 0.13 / 0.7183
cohort*time_period / COPAXONE / 1 / 1 / 2694.811 / 936.9261 / 858.4699 / 4531.153 / 8.27 / 0.0040
cohort*time_period / GILENYA / 1 / 1 / 6084.816 / 1542.689 / 3061.202 / 9108.431 / 15.56 / <.0001
cohort*time_period / INTERFERON / 1 / 1 / 2695.010 / 1008.041 / 719.2854 / 4670.735 / 7.15 / 0.0075
Scale / 1 / 34343.22 / 265.1532 / 33827.45 / 34866.87
Note:Thescaleparameterwasestimatedbymaximumlikelihood.
e_totalDiD.Group:pre_othDMTeq0Modelspec:link=identitydist=normal
TheGENMODProcedure
Model Information
/
Data Set / WORK.ALL2
Distribution / Normal
Link Function / Identity
Dependent Variable / e_total
Number of Observations Read
/ 8388
/
Number of Observations Used / 8388
Criteria For Assessing Goodness Of Fit
/
Criterion
/ DF
/ Value
/ Value/DF
/
Deviance / 8368 / 9.2038655E12 / 1099888321.7
Scaled Deviance / 8368 / 8388.0000 / 1.0024
Pearson Chi-Square / 8368 / 9.2038655E12 / 1099888321.7
Scaled Pearson X2 / 8368 / 8388.0000 / 1.0024
Log Likelihood / -99204.7265
Full Log Likelihood / -99204.7265
AIC (smaller is better) / 198451.4529
AICC (smaller is better) / 198451.5634
BIC (smaller is better) / 198599.1786
Analysis Of Maximum Likelihood Parameter Estimates
/
Parameter
/ DF
/ Estimate
/ Standard
Error
/ Wald 95% Confidence Limits
/ Wald Chi-Square
/ PrChiSq
/
Intercept / 1 / 34393.00 / 1446.343 / 31558.22 / 37227.78 / 565.45 / <.0001
cohort / AUBAGIO / 1 / -856.793 / 1685.809 / -4160.92 / 2447.333 / 0.26 / 0.6113
cohort / COPAXONE / 1 / -1299.74 / 908.8897 / -3081.13 / 481.6502 / 2.04 / 0.1527
cohort / GILENYA / 1 / 8196.966 / 1490.970 / 5274.719 / 11119.21 / 30.23 / <.0001
cohort / INTERFERON / 1 / -1998.33 / 975.7397 / -3910.74 / -85.9136 / 4.19 / 0.0406
time_period / 1 / 1 / 20459.75 / 615.7532 / 19252.90 / 21666.61 / 1104.05 / <.0001
cohort*time_period / AUBAGIO / 1 / 1 / 627.7477 / 1678.547 / -2662.14 / 3917.640 / 0.14 / 0.7084
cohort*time_period / COPAXONE / 1 / 1 / 2694.811 / 903.6915 / 923.6085 / 4466.014 / 8.89 / 0.0029
cohort*time_period / GILENYA / 1 / 1 / 6084.816 / 1487.967 / 3168.455 / 9001.177 / 16.72 / <.0001
cohort*time_period / INTERFERON / 1 / 1 / 2695.010 / 972.2842 / 789.3682 / 4600.652 / 7.68 / 0.0056
female / 1 / -1314.16 / 870.3774 / -3020.07 / 391.7499 / 2.28 / 0.1311
age3544 / 1 / 2911.243 / 1084.040 / 786.5649 / 5035.922 / 7.21 / 0.0072
age4554 / 1 / 7272.115 / 1085.129 / 5145.300 / 9398.929 / 44.91 / <.0001
age5564 / 1 / 8528.303 / 1231.351 / 6114.899 / 10941.71 / 47.97 / <.0001
REGION / 1 / 1 / -1996.29 / 1156.503 / -4262.99 / 270.4176 / 2.98 / 0.0843
REGION / 2 / 1 / -2392.60 / 1150.439 / -4647.41 / -137.777 / 4.33 / 0.0376
REGION / 3 / 1 / -2379.97 / 1081.666 / -4499.99 / -259.940 / 4.84 / 0.0278
REGION / 5 / 1 / -5030.69 / 3642.736 / -12170.3 / 2108.946 / 1.91 / 0.1673
cci / 1 / 3143.551 / 300.5743 / 2554.437 / 3732.666 / 109.38 / <.0001
pre_othDMT / 0 / 0.0000 / 0.0000 / 0.0000 / 0.0000 / . / .
pre_f_in / 1 / 18966.58 / 1027.885 / 16951.96 / 20981.20 / 340.48 / <.0001
Scale / 1 / 33125.00 / 255.7477 / 32627.52 / 33630.07
Note:Thescaleparameterwasestimatedbymaximumlikelihood.
e_totalDiD.Group:pre_othDMTeq0Modelspec:link=identitydist=normal
TheGENMODProcedure
Model Information
/
Data Set / WORK.ALL2
Distribution / Normal
Link Function / Identity
Dependent Variable / e_total
Number of Observations Read
/ 8388
/
Number of Observations Used / 8388
Criteria For Assessing Goodness Of Fit
/
Criterion
/ DF
/ Value
/ Value/DF
/
Deviance / 8362 / 9.4212714E12 / 1126676802.3
Scaled Deviance / 8362 / 8388.0000 / 1.0031
Pearson Chi-Square / 8362 / 9.4212714E12 / 1126676802.3
Scaled Pearson X2 / 8362 / 8388.0000 / 1.0031
Log Likelihood / -99302.6417
Full Log Likelihood / -99302.6417
AIC (smaller is better) / 198659.2833
AICC (smaller is better) / 198659.4642
BIC (smaller is better) / 198849.2164
Analysis Of Maximum Likelihood Parameter Estimates
/
Parameter
/ DF
/ Estimate
/ Standard
Error
/ Wald 95% Confidence Limits
/ Wald Chi-Square
/ PrChiSq
/
Intercept / 1 / 33644.23 / 1493.571 / 30716.88 / 36571.57 / 507.42 / <.0001
cohort / AUBAGIO / 1 / -927.914 / 1706.161 / -4271.93 / 2416.101 / 0.30 / 0.5865
cohort / COPAXONE / 1 / -1313.89 / 929.8586 / -3136.38 / 508.5955 / 2.00 / 0.1577
cohort / GILENYA / 1 / 8641.574 / 1510.117 / 5681.800 / 11601.35 / 32.75 / <.0001
cohort / INTERFERON / 1 / -1522.58 / 992.2824 / -3467.42 / 422.2602 / 2.35 / 0.1249
time_period / 1 / 1 / 20459.75 / 622.9831 / 19238.73 / 21680.78 / 1078.57 / <.0001
cohort*time_period / AUBAGIO / 1 / 1 / 627.7477 / 1698.256 / -2700.77 / 3956.268 / 0.14 / 0.7116
cohort*time_period / COPAXONE / 1 / 1 / 2694.811 / 914.3023 / 902.8117 / 4486.811 / 8.69 / 0.0032
cohort*time_period / GILENYA / 1 / 1 / 6084.816 / 1505.438 / 3134.212 / 9035.420 / 16.34 / <.0001
cohort*time_period / INTERFERON / 1 / 1 / 2695.010 / 983.7004 / 766.9929 / 4623.028 / 7.51 / 0.0062
female / 1 / -819.343 / 881.2044 / -2546.47 / 907.7858 / 0.86 / 0.3525
age3544 / 1 / 1885.654 / 1097.800 / -265.994 / 4037.303 / 2.95 / 0.0859
age4554 / 1 / 5010.941 / 1097.587 / 2859.709 / 7162.172 / 20.84 / <.0001
age5564 / 1 / 5700.082 / 1251.312 / 3247.556 / 8152.608 / 20.75 / <.0001
REGION / 1 / 1 / -1584.91 / 1173.235 / -3884.41 / 714.5881 / 1.82 / 0.1767
REGION / 2 / 1 / -1436.76 / 1164.733 / -3719.59 / 846.0760 / 1.52 / 0.2174
REGION / 3 / 1 / -1745.10 / 1094.971 / -3891.21 / 401.0014 / 2.54 / 0.1110
REGION / 5 / 1 / -4625.27 / 3687.661 / -11852.9 / 2602.414 / 1.57 / 0.2097
cci / 1 / 3743.733 / 302.6798 / 3150.492 / 4336.975 / 152.98 / <.0001
pre_othDMT / 0 / 0.0000 / 0.0000 / 0.0000 / 0.0000 / . / .
kol_sym1 / 1 / 2329.727 / 2248.234 / -2076.73 / 6736.184 / 1.07 / 0.3001
kol_sym2 / 1 / 3173.646 / 984.1902 / 1244.668 / 5102.623 / 10.40 / 0.0013
kol_sym3 / 1 / 4061.816 / 1131.512 / 1844.093 / 6279.538 / 12.89 / 0.0003
kol_sym4 / 1 / 11167.48 / 1876.269 / 7490.055 / 14844.90 / 35.43 / <.0001
kol_sym5 / 1 / 606.3687 / 2207.053 / -3719.38 / 4932.114 / 0.08 / 0.7835
kol_sym6 / 1 / 3136.954 / 1123.403 / 935.1246 / 5338.783 / 7.80 / 0.0052
kol_sym7 / 1 / 6760.254 / 840.3653 / 5113.168 / 8407.340 / 64.71 / <.0001
Scale / 1 / 33513.94 / 258.7506 / 33010.62 / 34024.94
Note:Thescaleparameterwasestimatedbymaximumlikelihood.

Model parameters for difference-in-difference (DiD) regression analysis in ARR, unadjusted and adjusted for differences in baseline patient demographics and clinical characteristics

/ DMT Cohorts /
COPAXONE / INTERFERON / GILENYA / AUBAGIO / TECFIDERA /
All / pre ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.32 / 0.36 / 0.44 / 0.38 / 0.41
post ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.34 / 0.35 / 0.30 / 0.36 / 0.30
diff_ARR / Mean / 0.02 / -0.02 / -0.14 / -0.02 / -0.11
Naive / pre ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.31 / 0.34 / 0.41 / 0.36 / 0.43
post ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.32 / 0.32 / 0.30 / 0.35 / 0.29
diff_ARR / Mean / 0.02 / -0.01 / -0.11 / -0.01 / -0.14
Experienced / pre ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.44 / 0.56 / 0.46 / 0.39 / 0.39
post ARR(IP pdx=340 OR OP+IV/high dose 500mg RX steroid) / Mean / 0.43 / 0.52 / 0.29 / 0.37 / 0.30
diff_ARR / Mean / -0.01 / -0.04 / -0.16 / -0.02 / -0.09
ARR DiD. Group: pre_othDMT eq 0 Model spec: link=log dist=poisson

The GENMOD Procedure

Model Information /
Data Set / WORK.ALL2
Distribution / Poisson
Link Function / Log
Dependent Variable / arr
Number of Observations Read / 8388
Number of Observations Used / 8388
Criteria For Assessing Goodness Of Fit /
Criterion / DF / Value / Value/DF /
Deviance / 8378 / 8277.0408 / 0.9879
Scaled Deviance / 8378 / 8277.0408 / 0.9879
Pearson Chi-Square / 8378 / 11256.3138 / 1.3436
Scaled Pearson X2 / 8378 / 11256.3138 / 1.3436
Log Likelihood / -5902.0600
Full Log Likelihood / -6485.8393
AIC (smaller is better) / 12991.6787
AICC (smaller is better) / 12991.7049
BIC (smaller is better) / 13062.0242
Analysis Of Maximum Likelihood Parameter Estimates /
Parameter / DF / Estimate / Standard Error / Wald 95% Confidence Limits / Wald Chi-Square / PrChiSq /
Intercept / 1 / -1.0359 / 0.0315 / -1.0976 / -0.9741 / 1081.22 / <.0001
cohort / AUBAGIO / 1 / 0.0079 / 0.0849 / -0.1585 / 0.1742 / 0.01 / 0.9263
cohort / COPAXONE / 1 / -0.1185 / 0.0475 / -0.2116 / -0.0254 / 6.22 / 0.0126
cohort / GILENYA / 1 / -0.0031 / 0.0760 / -0.1520 / 0.1459 / 0.00 / 0.9679
cohort / INTERFERON / 1 / -0.0723 / 0.0506 / -0.1713 / 0.0268 / 2.04 / 0.1529
time_period / 1 / 1 / -0.1964 / 0.0315 / -0.2581 / -0.1346 / 38.86 / <.0001
cohort*time_period / AUBAGIO / 1 / 1 / 0.1777 / 0.0849 / 0.0114 / 0.3441 / 4.38 / 0.0363
cohort*time_period / COPAXONE / 1 / 1 / 0.2255 / 0.0475 / 0.1323 / 0.3186 / 22.51 / <.0001
cohort*time_period / GILENYA / 1 / 1 / 0.0457 / 0.0760 / -0.1032 / 0.1946 / 0.36 / 0.5474
cohort*time_period / INTERFERON / 1 / 1 / 0.1776 / 0.0506 / 0.0785 / 0.2767 / 12.35 / 0.0004
Scale / 0 / 1.0000 / 0.0000 / 1.0000 / 1.0000
Note: / The scale parameter was held fixed.
ARR DiD. Group: pre_othDMT eq 0 Model spec: link=log dist=poisson

The GENMOD Procedure