Table 2.
Observational studies on non-medical switching
| 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 |
| Glintborg et al. 2016 (abstract) [105] and 2017 [52] | 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 |
| Flodmark et al. 2013 [88] (comment: Ekelund et al. 2014 [134]) | 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 |
ADA anti-drug antibody, AE adverse event, AS ankylosing spondylitis, ASDAS Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASFI Bath Ankylosing Spondylitis Functional Index, CD Crohn’s disease, CRP C-reactive protein, CT-P13 biosimilar infliximab, DAS Disease Activity Score, ESA erythropoietin-stimulating agent, FC faecal calprotectin, HAQ Health Assessment Questionnaire, Hb haemoglobin, HbA1c haemoglobin A1c, HGBI Harvey–Bradshaw Index, IBD inflammatory bowel disease, INX infliximab, IRR incidence rate ratio, MASES Maastricht Ankylosing Spondylitis Enthesitis Score, NR not reported, NS not significant, PASI Psoriasis Area and Severity Index, PMS Partial Mayo Score, PsA psoriatic arthritis, rhGH recombinant human growth hormone, RP reference product, SAE serious adverse event, SD standard deviation, SpA spondyloarthritis, T1DM type 1 diabetes mellitus, T2DM type 2 diabetes mellitus, TEAE treatment-emergent adverse event, UC ulcerative colitis, VAS visual analogue scale
aData extracted from English-language abstract (full text in Italian)