Table 1.
Clinical studies (non-medical switching)
| Reference | Patients | Patients switched, n | Pre-switch treatment, duration | Post-switch treatment, duration | Efficacy | Safety | ADAs |
|---|---|---|---|---|---|---|---|
| Jorgensen et al. 2017 [53] | Mixed (CD, UC, SpA, rheumatoid arthritis, PsA, chronic plaque psoriasis) | 240 | INX RP, mean duration 6.8 years | CT-P13, follow-up 52 weeks | INX RP vs CT-P13: disease worsening, 26 vs 30%; adjusted risk difference − 4.4% (95% CI − 12.7 to − 3.9) within pre-specified non-inferiority margin of 15%; adjusted RR: 1.17 (95% CI 0.82–1.52). Remission: 61% in each group; adjusted rate difference: 0.6% (95% CI − 7.5% to 8.8%) | INX RP vs CT-P13: ≥ 1 TEAE: 70 vs 68%; infusion reactions: 4 vs 2%; serious TEAEs 10 vs 9%; discontinuation because of AE: 4 vs 3%. No deaths | At any time point, INX RP vs CT-P13: 11% vs 13% |
| Kay et al. 2015 (abstracts and poster) [55, 56] | Rheumatoid arthritis (N = 189) | 53 | INX RP (Remicade®), 16 weeks (study also included patients on BOW015 throughout, with no switch) | BOW015, 38 weeks | INX RP/BOW015 vs BOW015/BOW015: similar disease activity and disability scores (shown as graph; statistical analysis NR) | INX RP/BOW015 vs BOW015/BOW015, patients with ≥ 1 TEAE: 53 vs 48%; SAE: 6 vs 7%; infusion reaction: 2 vs 4%; discontinuation due to TEAE: 0 vs 1% | INX RP/BOW015 vs BOW015/BOW015, week 30: 47 vs 42%; at week 58: 66 vs 65% |
| Park et al. 2017 [61] | AS (N = 174) (PLANETAS open-label extension) | 86 | INX RP, 54 weeks (study also included patients on CT-P13 throughout, with no switch) | CT-P13, 48 weeks | Clinical response maintained at similar levels before and after switch, and similar in switch and non-switch groups (all P NS) | INX RP/CT-P13 vs CT-P13/CT-P13, proportion of patients with ≥ 1 TEAE during extension study: 71 vs 49%; considered related to study drug: 39 vs 22% | INX RP/CT-P13 vs CT-P13/CT-P13, proportion of patients with ADAs at week 102: 27 vs 23% (P NS) (all patients with ADAs also had nADAs) |
| Smolen et al. 2016 (abstract) [69] | Rheumatoid arthritis (N = 396) | 94 | INX RP, 54 weeks (study also included patients on INX RP or SB2 throughout, with no switch) | SB2, 24 weeks | Response rates were maintained and similar between groups (shown on graph) | Incidence of AEs and infusion-related reactions, INX RP/INX RP: 36 and 2%; SB2/SB2: 40 and 4%; INX RP/SB2: 36 and 3% | Newly developed ADAs, INX RP/INX RP: 15%; SB2/SB2: 14%; INX RP/SB2: 15% |
| Tanaka et al. 2017 [70] | With rheumatoid arthritis (N = 104) | 33 | INX RP, duration 54 weeks | CT-P13, duration 105 weeks | Mean DAS28 at end of follow-up, maintenance vs switch group: 3.2 vs 4.0; P NR); discontinuation because of lack of efficacy: 3 vs 3% | ≥1 AE, maintenance vs switch group: 90 vs 88%; discontinuation because of AE: 11 vs 24% | Maintenance vs switch group at end of follow-up: 16 vs 17%. New ADA post switch: 3 vs 3% |
| Yoo et al. 2017 [73] | Rheumatoid arthritis (N = 302) (PLANETRA open-label extension) | 144 | INX RP, 54 weeks (study also included patients on CT-P13 throughout, with no switch) | CT-P13, 48 weeks | Clinical response maintained at similar levels before and after switch, and similar in switch and non-switch groups (all P NS based on 95% CIs) | INX RP/CT-P13 vs CT-P13/CT-P13, proportion of patients with ≥ 1 TEAE during extension study: 54 vs 54%; considered related to study drug: 19 vs 22% | INX RP/CT-P13 vs CT-P13/CT-P13, proportion of patients with ADAs at week 102: 45 vs 40% (P NS) (all patients with ADAs also had nADAs) |
| Haag-Weber et al. 2009 [74] | With renal anaemia (N = 386) | 137 | ESA RP (Eprex/Erypo), 28 weeks (study also included patients on HX575 throughout, with no switch) | HX575, 28 weeks | Haemoglobin values, range, HX575/HX575 vs ESA RP/HX575: 11.6–11.9 g/dL vs 11.5–12.1 g/dL (CI for between-group difference in change from baseline within pre-specified equivalence boundaries); weekly dosage remained constant (median dosage change in both groups: 0%) | NR separately for post-switch period, except for number of deaths [9 (3.6%) in HX575/HX575 group; 5 (3.6%) in ESA RP/HX575 group] | NR separately for post-switch period |
| Harzallah et al. 2015 [75] | With renal anaemia (N = 53) | 53 | 1st epoetin NR, then epoetin alfa RP (Hemax; pre-switch), 15 days | Biosimilar epoetin alfa (Epomax), 43 days | Pre-switch vs post-switch haemoglobin levels, blood pressure and median drug doses similar (shown as graph; statistical analysis NR) | Pre-switch vs post-switch differences in AEs NR; 5 patients discontinued after switch: 2 because of abdominal pain (considered unrelated to study drug) and reason NR for other 3 (all had stable haemoglobin levels at drop-out) | NR |
| Wiecek et al. 2010 [81], Wizeman et al. 2008 [82] (two studies) | With renal anaemia (N = 481) | 481 (118 + 121 + 242, across 2 trials and open-label extension) | Epoetin alfa or epoetin zeta, ≥ 12 weeks | Epoetin zeta or epoetin alfa, ≥ 12 weeks | Pre- vs post switch: median haemoglobin levels and doses maintained within pre-specified equivalence margins | Incidence and nature of TEAEs similar between groups and appeared unaffected by switch | None detected |
| Hadjiyianni et al. 2016 [84], Ilag et al. 2016 [85] | With T1DM (N = 452 [ELEMENT 1]) | 207 | Insulin glargine RP (IGlar; Lantus®), duration NR (study also included patients on IGlar throughout, with no switch) | LY IGlar, 24 weeks | No significant differences in efficacy parameters through 52 weeks, but greater weight gain in IGlar/LY than IGlar/IGlar group (1.0 vs 0.2 kg; P = 0.035) | No significant difference in TEAEs and serious AEs | ELEMENT 1: no significant difference in ADA incidence |
| Hadjiyianni et al. 2016 [84], Ilag et al. 2016 [85], Rosenstock et al. 2015 [86] | With T2DM [N = 299 (ELEMENT 2)] | 155 | Insulin glargine RP (IGlar; Lantus®), duration NR (study also included patients on IGlar throughout, with no switch) | LY IGlar, 24 weeks | No significant differences in efficacy parameters through 52 weeks | No significant differences in TEAEs, but significantly fewer patients in IGlar/LY IGlar than IGlar/IGlar group experienced ≥ 1 SAE (3 vs 8%, P = 0.03) | Overall (any time post-baseline) ADA incidence significantly higher in IGlar/LY IGlar than IGlar/IGlar group (19 vs 8%, P = 0.01) (potentially because of baseline imbalances), but not when measured at 24-week time point |
| Romer et al. 2011 [92] (modelling Belleli et al. 2015 [91]) | With growth disturbances (N = 163) | 45 | Genotropin, 9 months (studies also included patients on Omnitrope® throughout, with no switch) | Omnitrope® (powder and/or solution), up to 75 months | Pre- vs post-switch: similar predicted (model-based analysis) vs observed growth data; height and velocity nearly identical and parallel between switch vs non-switch groups | TEAEs, 1st 9 months (before switch): in 36 patients (22%); 9–18 months: in 29 patients (18%) | 1st 9 months (before switch): in 2 patients (1%); 9–18 months: in 1 patient (0.6%) |
| Engert et al. 2009 [93] | Undergoing chemotherapy (N = 92) | 29 | Filgrastim RP, 1 chemotherapy cycle (study also included patients on XM02 throughout, with no switch) | XM02, ≤ 5 chemotherapy cycles | Febrile neutropenia incidence across all cycles, filgrastim RP/XM02 vs XM02/XM02: 41 vs 32 (P NS) | AE profile reported as being similar between groups (actual post-switch data NR) | NR |
| Gatzemeier et al. 2009 [94] | Undergoing chemotherapy (N = 240) | 79 | Filgrastim RP, 1 chemotherapy cycle (study also included patients on XM02 throughout, with no switch) | XM02, ≤ 5 chemotherapy cycles | Febrile neutropenia incidence in cycle 4, filgrastim RP/XM02 vs XM02/XM02: 3.3 vs 4.3% (P NS) | Data specifically for time period after switch NR | NR |
| Krendyukov et al. 2017 (abstract) [95] | Undergoing chemotherapy (N = 218) | 107 | Filgrastim RP or EP2006, 1 cycle (study also included patients on filgrastim RP or EP2006 throughout, with no switch) | 6 cycles of alternating treatment, switching between filgrastim RP and EP2006 | Switched vs reference, febrile neutropenia: 3.4 vs 0% (95% CI − 9.65 to 4.96; within predefined non-inferiority margin); infections: 9.3 vs 9.9%. Hospitalisation due to febrile neutropenia, n = 1 (switched patient in cycle 6) | Switched vs reference (all cycles), TEAEs related to filgrastim: 42.1 vs 39.2%; musculoskeletal or connective tissue disorders related to filgrastim: 35.5 vs 39.2% (including bone pain: 30.8 vs 33.3%) | None detected |
| Papp et al. 2017 [97]; Gooderham et al. 2016, (abstract) [96] | With plaque psoriasis (N = 350) | 77 | Adalimumab, 16 weeks (study also included patients on adalimumab or ABP501 throughout, with no switch) | ABP501, 36 weeksa | NR post-switch | TEAEs, 4 weeks post-switch: continued ABP501 vs continued adalimumab vs switched to ABP501: 23 vs 19% vs 16% | At week 20, continued ABP501 vs continued adalimumab vs switched to ABP501: 55 vs 60 vs 65%; nADAs: 7 vs 11 vs 13% |
| Weinblatt et al. 2016 (abstract) [98] | With rheumatoid arthritis (N = 506) | 125 | Adalimumab, 24 weeks (study also included patients on adalimumab or SB5 throughout, with no switch) | SB5, 28 weeks | Adalimumab/adalimumab vs adalimumab/SB5 vs SB5/SB5, response at 52 weeks: 71 vs 81 vs 77% (P NR); mean change in modified Sharp score: 0.50 vs 0.25 vs 0.17 (P NR) | Adalimumab/adalimumab vs adalimumab/SB5 vs SB5/SB5, ≥ 1 TEAE: 33 vs 38 vs 32%; serious infection: 0 vs 2 vs 0%; injection site reactions: 2 vs 0 vs 0% | Adalimumab/adalimumab vs adalimumab/SB5 vs SB5/SB5, incidence: 18 vs 17 vs 16% |
| Nasanov et al. 2016 (abstract) [99] | With rheumatoid arthritis (N = 160) | NR (approx. 80, based on study design) | RTX RP, 24 weeks, or BCD-020, 24 weeks | BCD-020 24 weeks or RTX RP 24 weeks | RTX RP/RTX RP vs RTX RP/BCD-020, ACR20 at week 48: 92.3 vs 77.8% (P = 0.25); BCD-020/RTX RP vs BCD-020/BCD020: 89.3 vs 96.0%, (P = 0.61). RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020 ACR70 at week 48: 34.6, 40.7, 39.3, 40.0% | AEs, RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020: 38, 57, 63, 44% | RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020: 0 vs 0 vs 0 vs 4% |
| Park et al. 2017 [60] | With rheumatoid arthritis (N = 58) | 20 | Rituximab, up to 72 weeks (study also included patients on CT-P10 throughout, with no switch) | CT-P10, up to 56 weeks | CT-P10/CT-P10 vs rituximab/CT-P10, mean change at week 24 vs baseline, after 1st course, DAS28-CRP: − 2.2 ± 1.15 vs − 2.2 ± 1.16 (P NS); DAS28-ESR: − 2.7 ± 1.17 vs − 2.4 ± 1.33 (P NS). Percentage achieving good or moderate EULAR-ESR and EULAR-CRP responses similar between groups for each time point (week 8, 16 and 24) | CT-P10/CT-P10 vs rituximab/CT-P10, AE: 24 vs 20%; SAE: 3 vs 5%; infusion-related reaction: 3 vs 5%; infection: 8 vs 10% | CT-P10/CT-P10 vs rituximab/CT-P10: 13 vs 15% (all since pre-switch). nADAs, n = 1 |
| Emery et al. 2016 (abstract) [101, 102] | With rheumatoid arthritis (N = 245) | 119 | ETN RP, 52 weeks (study also included patients on SB4 throughout, with no switch) | SB4, 48 weeks | Weeks 52–100, ETN RP/SB4 vs SB4/SB4, ACR20: 79 vs 78%; ACR50: 61 vs 60%; ACR70: 42 vs 43% (statistical analysis NR) | Weeks 52–100, ETN RP/SB4: ≥ 1 TEAE, n = 58 (49%); ≥ 1 SAE, n = 2 (2%); serious infections, n = 1 (1%); death, n = 0 (0%); SB4/SB4: ≥ 1 TEAE, n = 60 (48%); ≥ 1 SAE, n = 6 (5%); serious infections, n = 1 (1%); death (from hepatic cancer), n = 1 (1%) | Weeks 52–100, ETN RP/SB4: n = 1 (1%); SB4/SB4: n = 1 (1%) |
| Griffiths et al. 2017 [103] | With chronic plaque psoriasis (N = 531) | 196 | GP2015 or ETN, 12 weeks (study also included patients re-randomised to same treatment, with different dosing schedule, with no switch) | Patients with PASI improvement ≥ 50% re-randomised to series of 3 treatment switches to week 30, then continuation on last assigned treatment to week 52 | Baseline to week 52, mean scores and percentage changes in PASI score at all time points similar between continued GP2015 and ETN groups, and between pooled continued and pooled switched groups. Response rates increased over time in all treatment groups until week 30 and then remained stable to week 52 | ≥1 TEAE up to week 52, continued GP2015 vs continued ETN switched GP2015 vs switched ETN: 60 vs 57 vs 61 vs 59%. AEs of special interest, continued GP2015 vs continued ETN switched GP2015 vs switched ETN: 11 vs 5 vs 11 vs 5% | Non-nADAs: 1% in the switched ETN group at week 36 (receiving GP2015 for 12 weeks at time of finding); 2% in continued ETN group |
| Strowitzki et al. 2016 [104] | Undergoing ovarian stimulation (N = 147) | 67 | FSH RP (Gonal–f), 1 cycle in RCT (study also included patients on Ovaleap throughout, with no switch) | Ovaleap, 1 cycle in RCT plus ≤ 2 cycles in extension study | Gonal-f/Ovaleap vs Ovaleap/Ovaleap, mean number of oocytes retrieved, cycle 2: 12.1 vs 12.0; cycle 3, mean: 15.0 vs 12.3 (P NR) | Frequency of TEAEs similar in 2 groups; there were 2 drug-related TEAEs, both in Ovaleap group: 1 injection-site erythema, pruritis and haematoma, 1 lower abdominal pain | Detected in 6 patients (none with nADAs); NR separately for 2 groups |
ABP501 adalimumab biosimilar, ACR American College of Rheumatology, ADAs anti-drug antibodies, AE adverse event, AS ankylosing spondylitis, BCD-020 rituximab biosimilar, BOW015 infliximab biosimilar, CD Crohn’s disease, CI confidence interval, CRP C-reactive protein, CT-P10 biosimilar rituximab, CT-P13 biosimilar infliximab, DAS28 Disease Activity Score in 28 joints, EP2006 filgrastim biosimilar, ESA erythropoietin-stimulating agent, ESR erythrocyte sedimentation rate, ETN etanercept, EULAR European League Against Rheumatism, FSH follicle-stimulating hormone, GP2015 etanercept biosimilar, HX575 epoetin alfa biosimilar, INX infliximab, LY IGlar LY2963016 insulin glargine, nADAs neutralising anti-drug antibodies, NR not reported, NS not significant, PASI Psoriasis Area and Severity Index, PsA psoriatic arthritis, RCT randomised controlled trial, RR relative risk, RP reference product, RTX rituximab, SAE serious adverse event, SB2 infliximab biosimilar, SB4 etanercept biosimilar, SB5 adalimumab biosimilar, SpA spondyloarthritis, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus, TEAE treatment-emergent adverse event, UC ulcerative colitis, XM02 filgrastim biosimilar
aOf 175 patients on adalimumab, those with PASI of ≥ 50 at 16 weeks were re-randomized 1:1 to remain on adalimumab or switch to ABP501