TABLE 1.
Characteristics of Included Objective Studies
| Author, year | Country | Study type | Observation length | Sample size | Age, gender, subtype, MS duration, EDSS | Design/setting | DMT(s) | Comments | |
|---|---|---|---|---|---|---|---|---|---|
| Agashivala, 201341 | USA | AH, DC | 12 months | N = 1,891 | Age: M = 45.6, SD = 11.1 years; Gender: 76.4% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | FTY, IFNβ-1b, IFNβ-1a, GA | New oral DMT users | |
| Aungst, 201942 | USA | AH | 52 weeks | N = 35 (consented); N = 25 (analyzed) | Age: M = 41.1, SD= 11.6 years; Gender: 71.0% Female; Subtype: NR; MS duration: NR; EDSS: NR | Prospective/multicentre | DMF | ||
| Bayas, 201537 | Fifteen European Countries | AH | 12 months | N = 912 (safety population); N = 791 (completed) | Age: M = 36.3, SD = 10.3 years; Gender: 73.7% Female; Subtype: RRMS; MS duration: Analyzed subset: N = 710, M = 33.0,SD=49.8 months; EDSS: M = 1.8, SD = 1.4 | Prospective/multicentre | IFNβ-1a s.c | Commenced IFNβ-1a < 8 weeks prior to study enrollment | |
| Bonafede, 201339 | USA | DC | 24 months | N = 5,710 | Age: M = 44.6, SD = 10.4 years; Gender: 76.6% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | IFNβ-1a, IFNβ-1b, GA, FTY | ||
| Braune, 201643 | Germany | DC | 24 months; PM: M = 1037.8 (461.2) days | N = 433; PM: N = 198 (99 FTY, 99 iDMT) | Age: M = 40.1, SD = 9.8 years (PM only); Gender: 75.8% Female; Subtype: RRMS; MS duration: M = 7.4, SD = 5.9 years; EDSS: M = 2.3, SD = 1.5 | Retrospective/outpatient clinical data | IFNβ-1a, IFNβ-1b, GA, FTY | 1st injectable failed and switched to fingolimod or 2nd injectable. Analysis of 1 and 2 years for persistence; Propensity matched sample persistence and discontinuation across available observation days | |
| Bruce, 201014 | USA | AH | 8 weeks | N = 67 | Age: M = 46.2, SD = 10.6 years; Gender: 88.1% Female; Subtype: RRMS; MS duration: M=10.0, SD = 7.8 years; EDSS: M = 2.4, SD = 1.2 | Prospective/MS specialty clinic | GA, IFNβ-1a, IFNβ-1b | ||
| Burks, 201713 | USA | AH, DC | 12 months | N = 1,018 | Age: 18-24 (4.3%), 25-44 (14.2%), 35-44 (30.6%), 45-54 (32.0%), 55-64 (19.0%); Gender: 72.1% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | TFN, FTY, DMF | Injectable data combined intravenous, thus, were excluded | |
| Cerghet, 201044 | USA | AH | 12 months | N = 214 (eligible); N = 163 (completed); N = 111 (dispensed a DMT) | Age: M = 47.5, SD = 9.5 years; Gender: 81% Female; Subtype: RRMS; MS duration: M = 8.9, SD = 6.4 years; EDSS: M=4.9 | Retrospective/database claims | GA, IFNβ-1a, IFNβ-1b | ||
| Cohan, 201845 | USA | AH | 12 months | N = 708; N = 531 (no switch); N = 177 (switch) | Age: No switch: M = 47.5, SD = 9.9 years. Switch: M = 46.8, SD = 9.6 years; Gender: 78.5% Female (Switch and no switch groups); Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | IFNβ-1a, IFNβ-1b | Participants who switched DMTs versus those who remain consistent on one DMT for 12 months | |
| Cohen, 201546 | USA | AH | 24 months | N = 3,151 (enrolled); N = 2,966 (baseline); N = 2,410 (completed) | Age: M = 49.6, SD = 9.9 years; Gender: 80.9% Female; Subtype: RRMS, SPMS, PPMS; MS duration: M=9.6, SD = 8.3 years; EDSS: M = 3.0, SD = 2.5 | Prospective/specialty pharmacy | GA, IFNβ-1a, IFNβ-1b | ||
| Condé, 201947 | France | DC | 24 months | N = 346 | Age: M = 44.2, SD = 0.9 years; Gender: 80.3% Female; Subtype: RRMS; MS duration: M = 10.1, SD = 0.8 years; EDSS: M = 1.8, SD = 0.1 | Retrospective/clinical record | DMF, TFN | ||
| D’Amico, 201948 | Italy | DC | 24 months | N = 903 pwRRMS; N = 316 (TFN); N = 587 (DMF) | Age: M = 42.5, SD = 10.6 years; Gender: 67.5% Female; Subtype: RRMS; MS duration: M = 109.2, SD = 84.6 months; EDSS: TFN: 2.0 (1.5-3.5); DMF: 1.5 (1.0-3.0) | Retrospective/multicentre | DMF, TFN | ||
| Defer, 201849 | France | AH | M = 11.5 years | N = 15,039 | Age: NR; Gender: 73.9% Female; Subtype: RRMS, SPMS; MS duration: M = 11.5, SD = 9.7 years; EDSS: NR | Retrospective/multicentre | IFNβ-1a, IFNβ-1b, GA | Only examines first-line injectable DMTs adherence | |
| Deftereos, 201850 | Greece | AH | 12 months | N = 64 (enrolled); N = 47 (complete study) | Age: M = 36.2, SD = 11.2 years; Gender: 78.1% Females; Subtype: RRMS; MS duration: M = 2.1, SD = 3.0 years; EDSS: NR | Prospective/multicentre | IFNβ-1a s.c | ||
| Degil Esposti, 201740 | Italy | AH, DC | 36 months | N = 1,698 | Age: M = 40.0, SD = 10.7 years; Gender: 69.0% Female; Subtype: NR; MS duration: M = 5.9, SD = 6.3 years; EDSS: Range, 0-9 | Retrospective/administrative database | IFNβ-1a, IFNβ-1b, GA | ||
| Devonshire, 201651 | Canada | AH | 12 and 24 weeks | N = 162 (enrolled); N = 158 (analyzed) | Age: M = 37.4, SD = 9.8 years; Gender: 75.3% Female; Subtype: RRMS, SPMS; MS duration: M = 24.0, SD = 57.6 months; EDSS: M = 1.8, SD = 1.3. | Prospective/multicentre | IFNβ-1a s.c. | ||
| Duquette, 20199 | Canada | AH, DC | 24 months | N = 26,157 (compliance); N = 32,795 (discontinuation) | Age: NR; Gender: NR; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | IFNβ-1a, IFNβ-1b, GA, FTY, DMF, TFN | Demographics not reported | |
| Eriksson, 201852 | Sweden | DC | Median = 2.5 years | N = 400 | Age: DMF 1st: M = 35.3, SD = 9.8. DMF switch: M = 40.5, SD = 10.1; Gender: DMF 1st: 72.0% Female. DMF switch: 76.0% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/regional database | DMF | Compares DMF as 1st line and switch to DMF | |
| Ernst, 201753 | USA | DC | 24 months | N = 450 | Age: M = 45.5, SD = 12.1 years; Gender: 75.8% Female; Subtype: RRMS; MS duration: M=527.6, SD = 1600.5 days; EDSS: NR | Retrospective/administrative data | IFNβ-1a s.c., DMF | ||
| Evans, 20 1754; 201655 | Canada | AH, DC | 12-month adherence; M = 7.8, SD = 4.0 years discontinuation follow-up | N = 4,746 (2017); N = 4,830 (2016) | Age: M = 40.4, SD = 10.0 years; Gender: 75.8% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/administrative data | IFNβ-1a, IFNβ-1b, GA | Duplicate studies, both included as one reports MPR (2017) and one PDC (2016) | |
| Evans, 201256 | Canada | DC | Up to 14 years | N = 1,896 | Age: M = 40.2, SD = 9.5 years; Gender: 75.1% Female; Subtype: RRMS, SPMS; MS duration: NR; EDSS: Median, 2.5 (range, 0-8.5) | Retrospective/MS database | IFNβ-1a, IFNβ-1b, GA | ||
| Fernández, 201657 | Spain | AH | Up to 3 years | N = 258 | Age: M = 40.7, SD = 9.5 years; Gender: 67.8% Female; Subtype: RRMS; MS duration: M = 8.9, SD = 6.0 years; EDSS: M = 1.8, SD = 1.2 | Retrospective/multicentre | IFNβ-1a s.c. | ||
| Fernández-Fournier, 201558 | Spain | DC | Median = 34 months | N = 155 | Age: M = 37.0, SD = 9.0 years; Gender: 68.3% Female; Subtype: RRMS; MS duration: NR; EDSS: Median = 1.52, IQR = 1-3 | Retrospective/clinical records | GA | Compares GA as 1st line and switch to GA | |
| Gerber, 201759 | Canada | AH, DC | 12 months | N = 2,781 | Age: < 35 (25%), 35-55 (61.7%), 55-65 (11.8%), > 65 (1.5%); Gender: 73.8% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/administrative data | IFNβ-1a, IFNβ-1b, GA, FTY, TFN, DMF | ||
| Hansen, 201510 | Germany | AH | 24 months | N = 50,057 | Age: NR; Gender: NR; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/pharmacy claims database | IFNβ-1a, IFNβ-1b, GA | Demographics not reported | |
| Johnson, 201712 | USA | AH | 12 months | N = 1,498 | Age: M = 48.1, SD = 10.7 years; Gender: 76.7% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | FTY, DMF, TFN | ||
| Jones, 201360 | USA | AH | 24 months | N = 5,825 | Age: M = 44.4, SD = 10.1 years; Gender: NR; Subtype: RRMS; MS duration: NR; EDSS: NR | Retrospective/shared solution program | GA | Participants were enrolled in a medication support program | |
| Kleinman, 201061 | USA | AH | 12 months | N = 358 | Age: M = 40.7, SD = 5.9 years; Gender: 62.7% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/claims database | IFNβ-1a, IFNβ-1b, GA | Participants had to be employed for this study | |
| Kleiter, 201762 | Germany | AH | 24 weeks | N = 151 (enrolled); N=143 (analyzed) | Age: M = 41.2, SD = 11.5 years; Gender: 69.2% Female; Subtype: RRMS, CIS; MS duration: (n = 105), M = 15.2, SD = 29.4 months; EDSS: (n = 105) median, 2.0 (range, 0-6.5) | Prospective/multicentre | IFNβ-1b s.c. | ||
| Kozma, 201463 | USA | AH | 24 months | N = 4,606 | Age: M = 46.0, SD = 9.4 years; Gender: 78.7% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database claims | IFNβ-1a, IFNβ-1b, GA | ||
| Krol, 201764 | Netherlands and Germany | AH | Up to 5 years | N = 1,682 | Age: M = 40.1, SD = 10.7 years; Gender: 72.5% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/multinational | IFNβ-1a s.c. | No demographic data reported for the Netherlands | |
| Lafata, 200819 | USA | AH | 24 months | N = 224 | Age: M = 47.6, SD = 10.4 years; Gender: 77.2% Female; Subtype: RRMS; MS duration: NR; EDSS: NR | Retrospective/multispecialty practice | GA, IFNβ-1a, IFNβ-1b | Insured patients | |
| Lebrun-Frenay, 201965 | France | DC | Up to 5 years | N = 881 (enrolled); N = 852 (analyzed) | Age: M = 39.9, SD = 10.6 years; Gender: 75.8% Female; Subtype: RRMS; MS duration: M = 8.1, SD = 7.5 years; EDSS: M = 2.3, SD = 1.7 (n = 716) | Prospective/database claims | GA | ||
| Lugaresi, 201266 | Italy | AH | 12 weeks | N = 120 (recruited); N = 119 (intent-to-treat population); N = 109 (completed study) | Age: M = 37.9, SD = 9.7 years; Gender: 75.6% Female; Subtype: RRMS; MS duration: M = 5.8, SD = 5.3 years; EDSS: M = 2.1, SD = 1.2 | Prospective/multicentre | IFNβ-1a s.c. | ||
| McKay, 201767 | Canada | AH | 24 months | N = 326 (included); N = 135 (DMT users) | Age: M = 48.7, SD = 11.9 years; Gender: 74.5% Female; Subtype: RRMS, SPMS, PPMS; MS duration: M = 15.3, SD = 9.9 years; EDSS: Median, 2.5 (IQR, 2.0-4.0) | Retrospective/pharmacy claims | IFNβ-1a, IFNβ-1b, GA | ||
| Melesse, 201735 | Canada | AH, DC | M = 7.8 years | N = 721 | Age: M = 37.6, SD = 9.8 years; Gender: 74.2% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/administrative data | IFN β-1a, IFNβ-1b, GA | Subset study of Evans, 2016; 2017, specific to first DMT prescribed | |
| Moccia, 201668 | Italy | DC | > 5 years; M = 7.9, SD = 3.8 years | N = 499 | Age: M = 32.3, SD = 8.2 years; Gender: 63.1% Female; Subtype: RRMS; MS duration; M = 2.7, SD = 2.7 years; EDSS: M = 2.0, SD = 0.6 | Retrospective/clinical data | IFN β-1a, IFNβ-1b | Newly commenced on IFNβ-1a & 1b as first DMT | |
| Moccia, 201569 | Italy | AH | Up to 4 years | N = 114 | Age: M = 35.8, SD = 10.4 years; Gender: 71.1% Female; Subtype: RRMS; MS duration: M = 8.1, SD = 9.1 years; EDSS: M = 2.8, SD = 0.8 | Retrospective/clinical data | IFNβ-1a s.c | ||
| Munsell, 201770 | USA | AH, DC | 12 months | N = 8,382 | Age: M = 43.1, SD = NR years; Gender: 76.7% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/claims database | IFNβ-1a, IFNβ-1b, GA, TFN, FTY, DMF | Newly initiated treatment | |
| Oleen-Burkey, 201171 | USA | AH | 24 months | N = 839 | Age: M = 45.2, SD = 10.4 years; Gender: 81.3% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/administrative claims data | GA | ||
| Paolicelli, 201672 | Italy | AH | 24 months | N = 384 (recruited); N = 343 (12 months); N = 150 (24 months) | Age: M = 36.0, SD = 9.2 years; Gender: 67.2% Female; Subtype: RRMS; MS duration: Median, 74 months (range, 0-398); EDSS: Median, 2 months (range, 0-6) | Prospective/clinical database | IFNβ-1a s.c. | ||
| Pedersen, 201873 | Demark | AH | 12 weeks | N = 60 (recruited); N = 54 (analyzed) | Age: M = 43.7, SD = 7.9 years; Gender: 83.3% Female; Subtype: RRMS; MS duration: M = 6.7, SD = 4.5 years; EDSS: Median, 2.75 (range, 0-5) | Prospective/multicentre | IFNβ-1a s.c. | ||
| Prosperini, 201974 | Italy | DC | 12 months | Prematching: N = 621; PEG, N = 196, DMF, N = 265, TFN, N = 160 | Age: M = 41.9, SD = 10.7 years; Gender: 69.3% Female; Subtype: RRMS; MS duration: M = 11.0, SD = 7.4 years; EDSS: PEG (1.0 [0-5.5]); DMF (1.5 [0-0.5]); TFN (2.5 [0-5.5]) | Retrospective/multicentre | TFN, DMF, PEG | Data propensity matched; Prematching cohort demographics displayed | |
| Sabido-Espin, 201775 | USA | AH, DC | 36 months | N = 5,956 | Age: M = 44.0, SD = 10.7 years; Gender: 74.7% Female; Subtype: NR; MS duration; NR; EDSS: NR | Retrospective/insurance claims database | IFNβ-1a s.c | ||
| Sanchirico, 201976 | USA | AH | 12 months | N = 7,072 | Age: M = 55.0, SD = 10.0 years; Gender: 78.3% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/medical and pharmacy claims | GA, IFNβ-1a, IFNβ-1b, TFN, DMF, FTY | ||
| Schreiber, 201877 | Denmark | AH | 12 months | N = 195 (enrolled); N = 126 (12 months) | Age: M = 41.0, SD = 8.7 years; Gender: 66.7% Female; Subtype: RRMS; MS duration: M = 9.0, SD = 6.0 years; EDSS: M = 3.0, SD = 1.7 | Prospective/multicentre | FTY | Only Includes intervention study, but observational data used | |
| Settle, 201630 | USA | AH | 6 months | N = 30 (recruited); N = 13 (routine care); N = 17 (intervention) | Age: M = 48.0, SD = 10.8 years; Gender: 50.0% Female; Subtype: RRMS, SPMS; MS duration: NR; EDSS: Median 3-3.5, range 2.0-8.0 | Prospective/veterans’ affair medical centre | IFNβ-1a i.m. | Compares usual care to online web-based tool; Veterans’ Affair Medical Centre sample | |
| Shao, 201878 | USA | AH | M = 281.56 days | N = 6,003 | Age: M = 46.0, SD = 10.1 years; Gender: 77.5% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/commercial claims database | IFNβ-1a, IFNβ-1b, GA | ||
| Smith, 201579 | USA | DC | M = 554.2 days | N = 8,107 | Age: M = 43.1, SD = 10.7 years; Gender: 76.2% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/insurance claims database | IFNβ-1a | Newly commenced IFNβ-1a | |
| Solsona, 201780 | Spain | AH | Median, 979 days | N = 110 | Age: M = 38.8, SD = 9.3 years; Gender: 66.4% Female; Subtype: NR; MS duration: NR; EDSS: Median, 1.5 (range, 0-4.5) | Retrospective/multiple sclerosis clinic data | IFNβ-1a s.c. | ||
| Steinberg, 201036 | USA | AH | 3 years; reported in 12-month periods | N = 1,606 | Age: M = 51.8, SD = 9.8 years; Gender: 76.0% Female; Subtype: RRMS; MS duration: NR; EDSS: NR | Retrospective/database claims | IFNβ-1a, IFNβ-1b | ||
| Stockl, 201081 | USA | AH, DC | 8 months | N = 468 | Age: M = 53.2, SD = 10.2 years; Gender: 83.3% Female; Subtype: NR; MS duration; NR; EDSS: NR | Retrospective/insurance database claims | IFNβ-1a, IFNβ-1b, GA | Disease management program compared to retail and specialty pharmacy participant | |
| Tan, 201182 | USA | AH | 12 months | N = 2,446 | Age: M = 41.9, SD = 10.1 years; Gender: 74.9% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/insurance database claims | IFNβ-1a, IFNβ-1b, GA | ||
| Vieira, 201983 | USA | AH | 24 months | N = 4,563 | Age: M = 46.7, SD = 9.9 years; Gender: 78.2% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/database | FTY, TFN | ||
| Warrender-Sparkes, 201684 | International | DC | 12 months | N = 2,640 | Age: M = 32.9, SD = 10.0 years; Gender: 70.3% Female; Subtype: RRMS, SPMS, CIS; MS duration: NR; EDSS: Median, 2 (IQR 1, 2.5) | Retrospective/MBase registry | IFNβ-1a, IFNβ-1b, GA, FTY | Newly diagnosed, commencing DMT | |
| Williams, 201885 | USA | AH | 12 months | N = 381 | Age: M = 41.8, SD = 10.9 years; Gender: 82.8% Female; Subtype: NR; MS duration: NR; EDSS: NR | Retrospective/administrative database claims | FTY, GA | Hispanic and African American subgroups | |
| Zecca, 20 1738 | Switzerland | AH | 9 months | N = 56 (observation); N = 53 (evaluable data) | Age: Median, 49.0 (IQR 38, 55); Gender: 77.4% Female; Subtype: RMMS; MS duration: Median, 6.5 years (IQR, 38, 55); EDSS: Median, 2 (IQR 1,3.3) | Retrospective and prospective/multicentre | IFNβ-1a s.c | Includes a retrospective and prospective observation period | |
| Zhang, 201786 | Canada | AH | 12 months | N = 801 | Age: M = 41.5, SD = 9.5 years; Gender: 76.0% Female; Subtype: NR; MS duration: NR; EDSS: Median, 3 (IQR 2,4) | Prospective/clinical and administrative database | IFNβ-1a, IFNβ-1b, GA | ||
| Zhornitsky, 201587 | Canada | DC | 18 years | N = 1,471 | Age: M = 38.4, SD = 9.3 years; Gender: 75.3% Female; Subtype: RRMS; MS duration: M = 6.0, SD = 6.7 years; EDSS: Median, 2.0 years (IQR: 1.5-3.0; Range, 0-8.0) | Prospective/MS clinic | IFNβ-1a, IFNβ-1b, GA | ||
| Zimmer, 201788 | Switzerland | AH, DC | 24 months | N = 98 | Age: Median, 41.0 years (IQR: 31.0, 46.0; Range, 22.0-71.0); Gender: 79.6% Female; Subtype: RRMS; MS duration: Median, 4.6 years (IQR: 1.0, 11.4; Range, 0.2-36.4); EDSS: NR | Prospective/MS clinic database | FTY | ||
Notes: Unless otherwise stated, IFNβ-1a includes both intramuscular and subcutaneous administration. All studies are observational unless otherwise stated. Sample sizes included are reported statistics, not total sample, unless specified. Only baseline and preintervention data are reported for intervention studies. Where required, means and standard deviations were combined excluding IV medications data, using sample group statistics through an online calculator: https://www.statstodo.com/CombineMeansSDs_Pgm.php.
AH = adherence; CIS = clinically isolated syndrome; DC = discontinuation; DMF = dimethyl fumarate; EDSS = expanded disability status scale; FTY = fingolimod; GA = glatiramer acetate; IFNβ-1a = interferon beta-1a; IFNβ-1a i.m = interferon beta-1a intramuscular; IFNβ-1a s.c = interferon beta-1a subcutaneous; IFNβ-1b = interferon beta-1b; IQR = interquartile range; MPR = medication possession ratio; NR = not reported; pwRRMS = people with relapse remitting multiple sclerosis; PPMS = primary progressive multiple sclerosis; PDC = proportion of days covered; PEG = pegylated interferon; PM = propensity matched; RRMS = relapse remitting multiple sclerosis; SPMS = secondary progressive multiple sclerosis; TFN = teriflunomide.