Table 2.
Study details and results from all identified studies of RebiSmart® (adherence, clinical outcomes, and health care resources use)a
| Study name | Study objective | Study design | Indication | Sample size | Follow-up period | Key results |
|---|---|---|---|---|---|---|
| Bayas et al (2015)18 | To evaluate adherence to and effectiveness of treatment in patients with RMS using RebiSmart for self-injection of SC interferon β-1a | Multicenter, prospective, observational | RMS | 912 | 12 months or until ED | • Age in the safety population (mean ± SD) was 63.3±10.3 years • Mean cumulative adherence was 97.1±7.3% (range 30%–100%; n=791) • Adherence rates (mean ± SD) were similar in treatment-naive patients (97.3±6.5%; range 42%–100%; n=453) and patients starting interferon β-1a within 6 weeks before study entry (96.7±8.8%; range 30%–100%; n=200) • Mean adherence per patient since the last visit at 1 year or ED was 96.5±9.4% (range 20%–100%; n=759) • At month 12/ED, 72.4% (560/774) of highly adherent patients and 41.2% (7/17) of patients with a lower adherence were relapse-free • A significantly higher proportion of relapse-free compliant high-dose patients (>120 µg/week) compared with lower dose patients in clean patient subset (92.5% vs 86.7%; P=0.0146) at month 6 with nonsignificant trend remaining at week 12/ED (82.1% vs 76.6%) • AAR 0.3±0.7 in highly adherent patients (n=774) and 0.6±1.3 in less adherent patients (n=16) |
| Devonshire et al (2016)21 | To evaluate 24-week treatment adherence of RMS patients using RebiSmart® for SC injection of interferon β-1a | Multicenter, single-arm, observational | RMS | 162 | 96 weeks (24-week data were available in this publication) | • Patient age (mean ± SD) was 37.4±9.8 years • The proportion of patients with ≥80% adherence was 91.8% (95% CI 86.3, 95.2) at week 12; 82.9% (95% CI 76.2, 88.0) at week 24 • Similar treatment adherence in patients with and without anxiety at baseline (96.1% vs 95.2%, P=0.322 at week 12; 89.0% vs 89.0%, P=0.901 at week 24) |
| Fernandez et al (2016)19 | To determine long-term adherence to SC interferon β-1a treatment administered with the RebiSmart® | Multicenter, retrospective, observational | RRMS | 258 | Until device replacement (36 months maximum lifetime) treatment discontinuation | • Patient age (mean ± SD) was 40.7±9.5 years • Overall adherence was 92.6% (95% CI 90.6, 94.5) • 32% of patients (n=78) achieved an adherence rate of 100%, and 80.6% of patients (n=208) achieved an adherence rate of ≥90%; 13.2% of patients (n=34) showed an adherence of <80% • Over the study period, a slight decrease in adherence with a mean overall adherence of 94.0% (95% CI 92.0, 96.0) at 0–3 months and 90.4% (95% CI 87.4, 93.3) at the time of device replacement • The incidence of relapses decreased from 5.8% (n=258 at 0–3 months) to 4.0% (n=150 at 33–36 months) • Having experienced relapses from the beginning of treatment was significantly related to achieving an adherence of ≥80% (OR =3.06, 1.28–7.31) • Suboptimal adherence (adherence of ≥80%) was about three-times higher in subjects with relapses compared with those without relapses |
| Ghezzi et al (2017)30 | To evaluate the changes in quality of life of adolescents with RRMS receiving treatment with interferon β-1a administered subcutaneously using RebiSmart® (FUTURE study) | Multicenter, single-arm, observational, prospective study | RRMS | 50 | 52 weeks | • Adolescents (age 12–16 years) who completed the study (n=40) showed 12-, 24-, and 52-week adherence rates of 82.5%, 80.0%, and 67.5%, respectively • At end of treatment, 32 (80%) of patients were relapse-free • Self-reported quality of life: ○ PedsQL4.0 self-reported Total Scale score and all subscale scores tended to increase (nonsignificantly) from baseline to end of treatment; except for Emotional Functioning score, which showed a nonsignificant decline ○ A mean raw change over time of +0.44 points was found for PedsQL4.0 Total Scale score, with the highest improvement (+1.41) identified for the School Functioning scale • Parent-reported QoL: ○ PedsQL4.0 Total Scale score increased significantly from baseline to end of treatment (+5.27 points, P=0.041) ○ Significant increases also emerged in the parent-reported Psychosocial Health summary score (+5.90 points; P=0.015) and the School Functioning scale score (+7.84 points; P=0.029) • There was no difference in either adolescent self-reported or parent-reported PedsQL4.0 scores in relation to age (12–15 vs 16–8 years) |
| Järvinen et al (2017)76 | To investigate adherence measured by an electronic autoinjector device vs self-reported adherence and treatment convenience in subjects with RRMS | Multicenter, observational | RRMS | 31 | 24 weeks | • Patient age (mean ± SD) was 39.0±8.0 years • Mean adherence was 93.5% (95% CI 88.4, 98.2; device data); 96.6% (95% CI 94.3, 99.0; self-assessment) • Age groups 30–40 and >40 years had a mean adherence of 62% and 64%, respectively; the age group <30 years had a slightly higher mean adherence of 75% • Device found to ease patient’s treatment and perceived to be easy to use (>65% of patients) |
| Lugaresi et al (2012)28 | To assess short-term adherence to, and tolerability of, interferon β-1a administered via electronic autoinjection device in patients with RRMS (BRIDGE study) | Multicenter, single-arm, observational | RRMS | 119 | 12 weeks or early termination | • Patient age (mean ± SD) was 37.9±9.7 years • 88.2% of patients administered ≥80% of scheduled injections over 12 weeks • Significant decrease in adherence (P=0.001) from 100% through week 4 to 99.1% in weeks 5–8, to 89.0% in weeks 9–12 • Mean HADS depression (P=0.303) or anxiety (P=0.156) scores did not differ significantly from baseline • Mean (± SD) baseline PASAT score was similar in adherent and nonadherent patients (42.67±10.9 vs 42.86±13.0) |
| Lugaresi et al (2016)29 | To investigate long-term adherence to interferon β-1a administered using RebiSmart® among patients in a real-life setting (RIVER study; extension of BRIDGE study) | Multicenter, retrospective | RRMS | 57 | 20.5 months | • Patient age (mean ± SD) was 38.0±9.0 years • Overall adherence to RebiSmart® was 79.8% (median, 85.2%, range, 16%–100%) • There was no statistically significant difference in age (mean ± SD) of adherent and nonadherent patients in the entire study cohort (37.6±10.0 vs 38.1±8.6 years; P=0.845) • EDSS scores at baseline and last follow-up did not differ significantly between adherent and nonadherent patients (date not shown in publication) |
| Moccia et al (2015)22 | To investigate predictors of adherence to interferon β-1a | Retrospective analysis of prospectively collected data | RRMS | 114 | 1.5 years | • Patient age (mean ± SD) was 35.8±10.4 years • Adherence was 95.0±9.0% • Early missing (14.9%) was more likely to be associated with clinical relapse (OR =4.155; P=0.018), but not late missing (47.4%) (OR =1.454; P=0.408) vs fully adherent (37.7%) • Adherence was lower in early missing compared with late missing or fully adherent (P<0.001) • In different regression models, categories of time to first missing were not associated with age (P=0.865) |
| Paolicelli et al (2016)20 | To collect data on treatment adherence in a real-life setting, in order to identify predictors of adherence at baseline (TRACER study) | Multicenter, retrospective | RRMS | 384 | 12 months | • Patient age (mean ± SD) was 36.0±9.2 years • 89.3% of patients were adherent • Adherence decreased from 93.2% in patients aged 26–40 years (93.2%) to 87.5% in patients aged ≥41 years to 79% in patients ≤25 years (P=0.006) • 90.5% of patients with a baseline EDSS <4 showed ≥80% adherence (vs 71.4% in patients with EDSS score ≥4; P=0.016) |
| Pedersen et al (2018)26 | To evaluate patient adherence to treatment with SC interferon β-1a using RebiSmart® and assess injection-site reactions and treatment satisfaction | Multicenter, prospective, single-arm, observational | RRMS | 60b | 12 weeks | • Patient age (mean ± SD) was 43.7±7.9 years • 89% (n=48) of patients had ≥90% adherence to treatment • 94% (n=51) of patients had ≥75% adherence (95% exact CI 85, 99); only three (6%) patients had adherence <75% and could be defined as nonadherent according to the study protocol • Most patients (78%) rated convenience as the most important aspect of the device |
| Rau et al (2017)27 | To investigate adherence pattern and cognitive– behavioral variables using electronic autoinjector RebiSmart® | Multicenter, single-arm, prospective study | RRMS | 188 | 24 months | • Patient age varied from 18 to 65 years • 12-month data • Of 129 patients with 1-year adherence data, quantitative and qualitative adherence were 96.3% and 88.9%, respectively • 82% reached qualitative adherence of ≥80% • FSMC motor score increased by 9.4% (P<0.002) and cognitive score increased by 10.0%, respectively (P<0.035) • 24-month data • Of 62 patients with 2-year adherence data, quantitative and qualitative adherence were 93.4% and 84.6%, respectively • 74% reached qualitative adherence of ≥80% • Cognitive fatigue increased by 8.4% (P<0.038) |
| Solsona et al (2017)23 | To describe adherence to interferon β-1a using RebiSmart® and to explore the relationship between adherence and relapses in a Spanish cohort | Retrospective, observational | MS | 110 | 979 days (mean duration of treatment) | • Patient age (mean ± SD) was 38.8±9.3 years • Mean adherence was 96.5% (IQR 91.1–99.1) • Mean adherence was 98.7% (IQR 91.3–100) during the first 6 months and 97.6% (IQR 91.1–99.8) during the last 6 months • No statistically significant differences in adherence were detected regarding age (Spearman’s rank correlation coefficient rs =0.183, P=0.055) • Increased adherence was associated with better clinical outcomes, leading to lower relapse risk (OR =0.953; 95% CI 0.912, 0.995); each percentage unit increase in adherence decreased the likelihood of relapse by 4.7% |
| Willis et al (2014)24 | To assess adherence to SC interferon β-1a injections using data from RebiSmart® | Single-group, observational, retrospective | RMS | 225 | 24 months | • Patient age (mean ± SD) was 44.1±8.82 years • Mean adherence over 24 months was 95.0% (95% CI 93.6, 96.4) • Proportion of patients with ≥80% adherence was 91.1% (95% CI 86.6, 94.5) at 24 months • No significant differences in percentage adherence between age categories were seen at 12 months (P=0.099) or 24 months (P=0.126) |
| Zecca et al (2017)25 | To evaluate the relationship between subjectively reported and objective adherence of MS patients using RebiSmart® in Switzerland and explore variables associated with objective adherence | Multicenter, survey-based, retrospective, prospective | RRMS | 56 | 9 months | • Patient median (IQR) age was 49.0 (38.0–55.0) years • Median objective adherence was significantly higher in self-reported adherent (100%; IQR 98.8%–100%) than in self-reported nonadherent patients (93.4%; IQR 77.2%– 97.5%) (P=0.00001) • No difference between retrospective (98.8%; IQR 93%–100%) and prospective (98.8%; IQR 88.5%–100%) objective adherence (P=0.75) • Older age was significantly associated with higher objective adherence (OR=1.064; 95% CI 1.016, 1.114; P=0.008) • Median (IQR) age as per adherence rates were: 41.0 (31.5–48.0) in patients with low adherence rates; 48.5 (36.5–54.8) in patients with medium adherence and 53.5 (42.0–63.0) in patients with high adherence rates |
Notes:
a
Key results listed focus on the impact of the device on adherence to treatment and, if available, a correlation between adherence and efficacy outcomes;
b
60 patients were recruited. However, adherence data were obtained in 54 patients only due to technical problems with six devices.
Abbreviations: ED, early discontinuation; EDSS, Expanded Disability Status Scale; FSMC, Fatigue Scale for Motor and Cognitive Functions; HADS, Hospital Anxiety and Depression Scale; IFN, interferon; IQR, interquartile range; OR, odds ratio; PASAT, Paced Auditory Serial Addition Task; PedsQL, Pediatric Quality of Life Inventory; QoL, quality of life; RMS, relapsing multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SC, subcutaneous.