We believe that sufficiently powered and appropriately statistically analysed trials and pharmacovigilance studies, with long-term follow-ups and multiple switching sequences, are still needed to support decision-making around biosimilar interchangeability. |
In the interim, switching should remain a clinical decision made by the treating physician and the patient based on available evidence and individual patient circumstances. |
1 Introduction
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% |
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 |
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 | |
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 | |
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 | |
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 |
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 |
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 |
Reference | Patients | Patients switched, n | Pre-switch treatment, duration | Post-switch treatment, duration | Efficacy | Safety | ADAs |
---|---|---|---|---|---|---|---|
Abdalla et al. 2017 [43] | With inflammatory arthritis (N = 34) | 34 | INX RP, mean duration 70 months | Biosimilar INX, mean follow-up 16 months | 6 months before vs 6 months after switch: HAQ score, patient global assessment of disease activity, number of disease flares or medication dose similar (all P NS). Pain (29 mm vs 38 mm; P = 0.028) and CRP values (1.95 vs 4.0 mg/L; P = 0.001) significantly higher during longer follow-up | No significant difference in number of SAEs (2 vs 3), AEs (numbers NR) or infusion reactions (1 vs 1) during follow-up periods. 5 patients discontinued INX | NR |
Ala et al. 2016 (abstract) [44] | With IBD (N = 20) | 20 | INX RP, duration NR | CT-P13, 6 months post-switch | Most patients remained in clinical remission or improved during follow-up (actual numbers NR) | No significant AEs reported post-switch | NR |
Arguelles-Arias et al. 2017 [45] | With IBD (N = 120) | 98 | Originator INX, median duration 297 weeks, or INX-naive | CT-P13, follow-up 6 months | Remained in clinical remission, switched vs naïve, CD, 3 months: 88 vs 67%; 6 months: 84 vs 50%. UC, 3 months: 92 vs 44%; 6 months: 91 vs 67% | NR separately for the 2 treatment groups | NR |
Bennett et al. 2016 (abstract) [46] | With IBD (N = 104) | 104 | INX RP, median time 162 weeks | CT-P13, follow-up 6 months | Pre-switch vs post-switch, median CRP: 2 vs 2 (P = 0.81); median DAS: 1 vs 1 (P = 0.44); remission: 85 vs 81% (P = 0.51) | After switch: 4 patients had AEs (2 minor infusion reactions, 2 skin disease); 19 patients stopped treatment (6 electively, 9 loss of response, 4 for other reasons) | Pre-switch vs post-switch: 29 vs 27 patients (P = 0.88) |
Benucci et al. 2017 [47] | With SpA (N = 41) | 41 | Originator INX, median duration 74 months | Biosimilar INX, follow-up 6 months | 6 months before vs 6 months after switch, median BASDAI (2.6 vs 2.7), BASFI (2.2 vs 2.3), ASDAS-CRP (1.3 vs 1.4); DAS28-CRP (2.7 vs 2.7), MASES (0.2 vs 0.4), VAS pain (17 vs 18) (all P > 0.05). Median duration of morning stiffness 7.2 vs 5.8 (P = 0.02) | No significance difference in AEs (Fisher test P = 1.0; actual data NR). 1 patient stopped biosimilar INX because of severe palmoplantar psoriasis | 6 months before vs 6 months after switch: 27.3 vs 27.8 ng/mL (P = 0.98) |
Buer et al. 2017 [48] | With IBD (N = 143) | 143 | Originator INX, CD, median 87 months; UC, median 57 months | CT-P13, follow-up 6 months | Median change in DAS (HGBI for CD, PMS for UC), 0–3 months and 3–6 months: all 0. Clinical remission baseline vs 6 months, CD: 87 vs 81%; UC: 88 vs 95%. No significant change in CRP, Hb, FC, INX dose, dose interval or plasma INX levels post-switch. All P NS | Post-switch: AEs in 17 patients (3 with UC, 14 with CD); 5 infusion reactions (leading to treatment discontinuation in 1 patient) | Baseline vs new post-switch: n = 2 vs n = 3 patients |
Dapavo et al. 2016 [49] | With plaque psoriasis (N = 35) | 30 | INX RP, median duration 237 weeks | CT-P13, median follow-up 23 weeks with median 4 cycles | Pre- vs post-switch (end of follow-up), PASI score: P NS (actual values NR); VAS scores: P NS (actual values NR) | Post-switch: herpes zoster (1 patient) | NR |
Fiorino et al. 2017 [50] | With IBD (N = 547) | 97 | INX RP, duration NR; mean number of infusions 18 [study also included patients with no treatment (naive) or other biologic pre-switch] | CT-P13 switch group, median follow-up 6.6 months | INX RP/CT-P13 vs naive/CT-P13 vs other/CT-P13, estimated probability of response at 24 weeks: 79 vs 74 vs 63%. Primary failure: 0 vs 10 vs 11% (P = 0.005). Estimated probability of treatment persistence at 24 weeks: 92 vs 82 vs 71% | SAEs, INX RP/CT-P13 vs naive/CT-P13 vs other/CT-P13: 12 vs 7 vs 22%; infusion reactions: 7 vs 3 vs 15%. IRR naïve vs switched for SAEs and infusion reactions leading to drug withdrawal: 1.10 (P NS) and 1.88 (P NS), respectively | NR |
Gentileschi et al. 2016 (letter to editor) [51] | With rheumatic diseases (N = 23) | 23 | INX RP (Remicade®), mean duration: 72 months | CT-P13 (Inflectra®), mean 1.7 months | 7/23 patients (30%) relapsed after switch (5 switched back to INX RP, of whom 4 improved) | NR | NR |
With rheumatoid arthritis, SpA or PsA (N = 802) | 802 | INX RP, duration 6.8 years | CT-P13, median follow-up 413 days | Disease activity, 3 months pre- vs post-switch: no clinically relevant differences. unchanged in majority of patients | Post-switch treatment discontinuation: 132 patients (lack of effect, n = 71, AEs, n = 37) | Baseline vs post-switch (data from 2016 abstract, n = 96): 15 vs 16% (P = 0.7) | |
Jung et al. 2015 [54] | With IBD (N = 110) | 36 | INX RP, duration NR (study also included naive patients started straight on CT-P13 treatment, with no switch) | CT-P13, duration up to 54 weeks | INX RP/CT-P13: efficacy maintained in 31/36 patients, CT-P13 discontinued in 3 patients because of lack of efficacy and in 1 patient who wanted to switch back to INX RP (reason NR) | INX RP/CT-P13: AEs, n = 1 patient (skin rash and arthralgia) | NR |
Nikiphorou et al. 2015 [58] | With established rheumatic diseases (N = 39) | 39 | INX RP (Remicade®), mean duration 4 years | CT-P13, median follow-up 11 months | Patient-reported outcomes (including pain, fatigue) similar pre-switch vs post-switch (all P NS) | 11 patients (28%) discontinued CT-P13: ADAs [sample taken before switch, n = 3; re-activation of tuberculosis, n = 1; new-onset neurofibromatosis, n = 1; subjective reasons (details NR), n = 6 (5 restarted INX RP)] | Not assessed after switching |
Rahmany et al. 2016 (abstract) [62] | With IBD (N = 78) | 78 | INX RP; median treatment duration: CD 46 months, UC 25 months | CT-P13, 4–6 months | Pre- vs post-switch, remission, CD: 67 vs 72%; UC: 60 vs 85%; mean CRP: 5.4 vs 5.6 (P NS); UC: 3.1 vs 3.0% (P NS) | 1 infusion reaction. Rate of mild AEs similar pre- and post-switch (actual data NR). Post-switch treatment discontinuation: 5 patients (3 biological class switch, 1 infusion reaction, 1 deep remission) | NR |
Razanskaite et al. 2017 [63] | With IBD (N = 143) | 143 | INX RP, median number of infusions 10 | CT-P13, follow-up: ≥ 3 infusions | Pre- vs post-switch, median IBD-Control-8 score: 11 vs 14 (P = 0.041). Mean CRP, albumin levels, platelet count, white cell count: all P NS. Treatment persistence INX RP historical cohort vs switch cohort: P NS | Pre- vs post-switch, joint pains: 26 vs 14%; headaches: 22 vs 17%; infections: 13 vs 9% | Pre- vs post-switch: 40 vs 40% of patients (P NS) |
Schmitz et al. 2017 [67] | With rheumatoid arthritis, PsA, AS, SpA, psoriasis or arthritis with UC (N = 27) | 27 | INX RP, median duration 143 months | CT-P13, duration approximately 12 months | Median INX trough levels, CRP levels, DAS28: all P NS | Post-switch, therapy discontinuation because of AEs: 2 patients (hyperventilation, suspected vasculitis); because of higher disease activity: 2 patients | Post-switch: no new detected |
Sheppard et al. 2016 (abstract) [65] | With rheumatic diseases (N = 25) | 25 | INX RP, duration NR | CT-P13, duration NR | 1 patient (4%) reported loss of disease control post-switch; no significant difference in CRP values before and after switch (actual data NR) | 4 patients (16%) developed AEs after switching: flu-like symptoms (n = 1), inflamed foreskin (n = 1), pruritic rash (n = 2); all were switched back to INX RP | NR |
Sieczkowska et al. 2016 [66] | With paediatric IBD (N = 39) | 39 | INX RP, mean duration 67 weeks | CT-P13, mean follow-up 8 months | Remission rate, at baseline: 69%; after 1st CT-P13 infusion: 75%; after 2nd CT-P13 infusion: 83%; statistically significant improvement in disease activity index | After switch: 3 patients (8%) with infusion reactions (1 leading to discontinuation), 1 with varicella zoster (leading to discontinuation), 7 with infections of upper respiratory tract | NR |
Smits et al. 2016 [68] | With IBD (N = 83) | 83 | INX RP, median duration 25 months | CT-P13, duration 16 weeks | Baseline (at switch) vs 16 weeks post-switch: no significant changes in efficacy parameters (disease activity; percentage in clinical remission; inflammatory biomarkers), but 4 patients needed additional medication to control increased disease activity | 24 patients (29%) reported AEs; 6 patients (7%) had suspected drug-related AEs: pruritis after infusion (n = 2); dizziness/tingling sensation after 1st or 2nd infusion (n = 2); warm sensation after 2nd infusion (n = 1); arthralgia (n = 1) | ADAs detected in 7 patient (8%), of whom 5 also had ADAs at baseline |
Tweehuysen et al. 2016 (abstract) [71] | With rheumatoid arthritis, PsA, or SpA (N = 192) | 192 | Innovator INX, duration NR | Biosimilar INX, follow-up 6 months | Baseline vs 6 months for rheumatoid arthritis and PsA, mean DAS28-CRP: 2.2 (SD 0.9) vs 2.2 (SD 0.84) (P NS); for SpA, mean BASDAI: 3.8 vs 4.3 (change + 0.5, 95% CI 0.12–0.89; P = 0.01). Median CRP levels: 1.5 mg/L vs 1.0 mg/L (P NS). Discontinuation because of loss of efficacy: 18% | Post-switch treatment discontinuation: 23 because of AEs (most frequent: fatigue, n = 10; malaise, n = 5; headache, n = 3), 2 because of infusion reaction. No SAEs reported | Baseline vs 6 months: 47 vs 38% |
Yazici et al. 2016 (abstract) [72] | With rheumatoid arthritis (N = 3018) | 148 | INX RP, duration NR | CT-P13, mean 9–12 months | Therapy discontinuation, continuation vs switched groups: 38% (average time to discontinuation 256 days) vs 82% (average time to discontinuation 124 days; 70% switched back to INX RP) | NR | NR |
Lopez et al. 2014 (abstract) [77] | Undergoing chemotherapy (N = 28) | 28 | Epoetin alfa, darbepoetin alfa; 12 months | Epoetin zeta, 12-months | Mean Hb, pre-switch epoetin alfa vs post-switch: 10.8 vs 11.1 g/dL (P NS); pre-switch darbepoetin vs post-switch: 9.9 vs 10.9 g/dL (P = 0.01). Post-switch dose increase to maintain target Hb: 46% of patients | NR | NR |
Morosetti et al. 2017 [79]a | With chronic renal failure (N = 87) | 87 | ESA, 6 months | Biosimilar, 6 months | Pre- vs post-switch Hb, ferritin, transferrin saturation: all P NS; mean monthly epoetin consumption/patient: 52,460 vs 49,517 Ul (P NS) | No changes in incidence of thrombosis or cardiovascular events | NR |
Balili et al. 2015 (abstract) [83] | With T2DM (N = 24) | 24 | Humulin 70/30, duration NR | Wosulin 70/30, duration NR | Pre- to post-switch mean HbA1c decreased by 1.3%, total insulin dose/day increased by 2.4 units. Target HbA1c was achieved (specific results NR) | NR | NR |
Segal et al. 2013 [87] | With T1DM or T2DM (N = 77) | 77 | Actraphane, Humulin 30/70 or Insuman, insulin duration 7 years | Biosulin 30/70, 6 months | Baseline (at switch) vs post-switch: no significant change in HbA1c, neither overall nor in subgroups by type of diabetes; small, significant increase in insulin dose | No severe hypoglycaemic episodes reported; other details NR | NR |
With growth disturbances (N = 98) | 98 | Genotropin RP, duration NR (graph suggests up to 2 years) | Omnitrope®, duration NR (graph suggests up to 1.5–2 years) | Growth in height after switch: modelled vs actual data suggest no impact of switch on growth | Number of patients with TEAEs in 12 months after switch: 18 patients; injection site pain: 18 (of whom 6 subsequently switched back to originator preparation) | NR | |
Gila et al. 2014 (abstract) [89] | With growth disturbances (N = 20) | 20 | rhGH RP, mean duration 38 months | Omnitrope®, follow-up 36 months | Height velocity, 18 months before switch: 9 ± 2 cm/year; at switch: 6 ± 1 cm/year; 18 months after switch: 7 ± 3 cm/year (statistical analysis NR) | No TEAEs reported after switch; 3 patients had transitory problems with Omnitrope® device | NR |
Rashid et al. 2014 [90] | With growth disturbances (N = 103) | 103 | Non-Omnitrope® rhGH (Humatrope®, Norditropin®, Nutropin®, Saizen®), duration ≥ 15 months | Omnitrope®, duration 15 months | Height velocity, 6 months before switch: 6.4 cm/year; at switch: 6.0 cm/year; 6 months after switch: 5.9 cm/year; 12 months after switch: 5.3 cm/year (study authors comment that this decline is expected/associated with advancing age) | NR | NR |
2 Methods
2.1 Systematic Literature Searches
2.2 Study Eligibility and Data Extraction
2.3 Role of Funding Source
3 Results
Reference | Patients | Patients switched, n | Pre-switch treatment, duration | Post-switch treatment, duration | Efficacy | Safety | ADAs |
---|---|---|---|---|---|---|---|
Kolar et al. 2017 [57] | With IBD (N = 74) | 74 | INX RP, mean duration 3 years | Biosimilar INX, duration 24 weeks | Baseline (at switch) vs 56 weeks post-switch, CRP: 4.3 vs 3.3 mg/L (P = 0.89); faecal calprotectin: 135 vs 199 μg/g (P = 0.17); stable disease activity: 72 vs 78% (P NR). Median difference in both HBI and SCCAI from week 0 to week 56 = 0 | Frequency and type of AE similar before and after switch; no infusion reactions reported in switch cohort. Treatment discontinuation because of AE, CD: 2 patients (arthralgia, fibrous dysplasia in maxilla); UC: 2 patients (lack of response) | ADA positive: 9.5 vs 6% (P = 0.54 |
Park et al. 2015 [59] | With IBD (N = 173) | 60 | INX RP, duration: NR (study also included naive patients started straight on CT-P13 treatment, with no switch) | CT-P13, duration: 30 weeks | Disease worsened (remission not maintained/achieved) in 11% of patients in switch group during 30-week follow-up | Treatment-related TEAEs of special interest, n for naive vs switch, anaphylactic reaction: 0 vs 1; tuberculosis: 1 vs 0; infusion-related reaction: 0 vs 3; no cases of pneumonia or malignancy | NR |
Rubio et al. 2016 (abstract) [64] | With rheumatic diseases (N = 78) | 53 | INX RP (Remicade®), duration NR (study also included naive patients started straight on biosimilar INX, with no switch) | Biosimilar INX (Remsima®), follow-up 9 months | 4 patients (5%) in switch group and 1 patient (4%) in naive group discontinued because of loss of efficacy | In switch group, 1 patient discontinued because of cutaneous leishmaniasis. In naive group, 1 patient each discontinued because of photosensitivity, bronchospasm, urticaria | NR |
Hörbrand et al. 2013 [76] | With CKD (N = 6177) | 507 | Originator short-acting epoetin alfa, epoetin beta, epoetin delta, epoetin theta, long-acting darbepoetin alfa, methoxy polyethylene glycol epoetin beta, duration ≥ 3 months | Biosimilar short-acting epoetin alfa, epoetin zeta, duration ≥ 3 months | No change in median defined daily doses consumption when switched | NR | NR |
Minutolo et al. 2016 [78] | Under-going haemodialysis (N = 149) | 149 | Reference epoetin, darbepoetin, duration NR (analysis 12 weeks) | Biosimilar epoetin (HX575, SB309), duration 24 weeks | Baseline vs post-switch, haemoglobin: 11.1 g/dL vs 11.0 g/dL (P NS); dose: 8765 IU/week vs 10,886 IU/week (P = 0.001) | NR | NR |
Ohta et al. 2014 [80] | With renal anaemia (N = 30) | 30 | Epoetin beta, duration 3 months | Epoetin kappa, duration 3 months | Haemoglobin levels predominantly stable (shown graphically, statistical analysis NR) | NR | NR |
Roy et al. 2013 [100] | With non-Hodgkin’s B cell lymphoma (N = 223) | 29 | Rituximab RP (Mabthera®) or biosimilar (Reditux™) (≥ 4 cycles with 1 brand) | Rituximab biosimilar (Reditux™) or RP (Mabthera®) (≥ 4 cycles with 1 brand) | All cycles with Mabthera® vs ≥ 4 cycles with Mabthera® (i.e. includes switched patients), complete remission: 75 vs 74%; partial remission: 14 vs 14%; 5-year survival: 66 vs 64%; 5-year progression-free survival: 72 vs 71%. All cycles with Reditux™ vs ≥ 4 cycles with Reditux™ (i.e. includes switched patients), complete remission: 82 vs 80%; partial remission: 13 vs 17%; 5-year survival: 76 vs 71%; 5-year progression-free survival: 81 vs 75% | NR separately for switch group | NR |