Table 3.
Published observational studies
| Study | N | Intervention | Duration of follow-up | Effectiveness of medication | Response and/or remission criteria | Discontinuation rate | Immunogenicity | Safety |
|---|---|---|---|---|---|---|---|---|
| Avouac J et al., 2018, France |
N = 64 n = 41 CD n = 23 UC |
Switch to CT-P13 | 3 biosimilar infusions |
HBI (baseline; follow-up): 0.83; 0.56 PM (baseline; follow-up): 0.71; 0.33 No significant change in disease activity scores |
N/A | 22% for CD patients by 3rd infusion; 13% of all IBD at a mean follow-up of 34 weeks | No significant change in serum trough concentration after switch | No SAEs |
| Binkhorst L et al., 2018, The Netherlands |
N = 197 n = 135 CD n = 62 UC |
Switch to CT-P13 | 16 weeks | Loss of response: 5.5% (n = 11) | Increase in disease-related symptoms as established by the physician and/or changes in treatment | 10% | No significant change in serum trough concentration after switch |
1 severe acute IRR No SAEs or unexpected AEs |
| Fiorino G et al., 2018, Italy and Spain |
IFX: n = 13 CT-P13: n = 9 Switch: n = 12 |
Maintenance on IFX Initiated on CT-P13 Switch to CT-P13 |
N/A | N/A | N/A | N/A |
16.7% (2/12) developed ADA after switch to CT-P13; 100% cross-reactivity of ADAs between IFX, CT-P13, and SB2 |
N/A |
| Kang B et al., 2018, Korea |
N = 74 (pediatric) n = 60 CD n = 14 UC |
Maintenance on IFX (n = 36) Switch to CT-P13 (n = 38) |
1 year |
Sustained remission rate: IFX: 77.8%, Switch: 78.9% (p = 1.00) |
Clinical remission lasting for at least 2 years plus mucosal healing identified on 2 consecutive annual follow-up colonoscopies |
IFX: 13.9%, Switch: 7.9% (p = 0.649) |
Therapeutic trough levels: IFX: 90.3%, Switch: 88.6%; New ADA: IFX: n = 2, Switch: n = 1 |
27 AEs in IFX vs. 30 in switch group |
| Schmitz EMH et al., 2018, The Netherlands |
N = 133 n = 85 CD n = 48 |
Switch to CT-P13 | 1 year | Disease worsening: 9% (n = 12; with 2 deemed not switch-related) | N/A | 26% | 3 developed ADAs after switch | 9.8% discontinued treatment due to AEs |
|
Strik A et al., 2018, Belgium and The Netherlands (SECURE study) |
N = 120 n = 61 CD n = 59 UC |
Switch to CT-P13 | 16 weeks |
Loss of response at 16 weeks: CD: 12% UC: 24% |
Increase in HBI > 4 in CD patients and in SCCAI > 2 in UC patients | N/A |
Geometric mean ratio of drug concentration (week 16 vs. baseline): CD: 107.6% (97.4–118.8) UC: 110.1% (90% CI 96.0–126.3); 3 developed new ADAs after switch |
6 SAEs, with only 1 (perianal abscess) deemed related to study treatment |
| Argüelles-Arias F et al., 2017, Spain |
N = 120 n = 67 switch, 13 naïve CD n = 31 switch, 9 naïve UC |
Switch to CT-P13 (n = 98) Naïve patients initiated on CT-P13 (n = 22) |
6 months |
Sustained remission rate in switch patients: CD: 87.5% at 3 months, 83.9% at 6 months UC: 92% at 3 months, 91.3% at 6 months |
No need for steroids, surgery or increased dose in both CD and UC switch patients | N/A | N/A | SAEs in 7.5% of total study population |
| Argüelles-Arias F et al., 2017, Spain |
N = 98 n = 67 CD n = 31 UC |
Switch to CT-P13 | 1 year |
Disease worsening at 1 year: CD: 30.2% UC: 19%; |
N/A |
CD: 9% UC: 19.4% |
N/A | SAEs in 11.2% of patients |
|
Sustained remission rates: CD: 83.6% at baseline, 62.7% at 1 year UC: 80.6% at baseline, 64.3% at 1 year |
Maintenance of HBI ≤ 4 in CD patients or PM ≤ 2 in UC patients, without the need for steroids, surgery or increased dose after switching | |||||||
| Buer LCT et al., 2017, Norway |
N = 143 n = 99 CD n = 44 UC |
Switch to CT-P13 | 6 months |
Sustained remission rates: CD: 87% at baseline, 81% at 6 months UC: 88% at baseline, 95% at 6 months |
Maintenance of HBI ≤ 4 in CD patients and PM < 2 in UC patients | 3% | 3 developed ADAs after switch |
Rate of IRRs 0.7% (5/750) 17 AEs reported, 2 resulting in treatment discontinuation |
| Eberl A, et al., 2017, Finland |
N = 62 n = 32 CD n = 30 UC |
Switch to CT-P13 | 3 biosimilar infusions | No change in disease activity (HBI, PM score) | N/A | N/A |
2 developed ADAs after switch; Trough levels: CD: 5.75 mg/L at baseline, 5.5 mg/L at 3rd infusion (p = 0.05) UC: 5.2 mg/L at baseline, 4.25 mg/L at 3rd infusion (p = 0.019) |
Rate of IRRs 2.5% (4/156 infusions) |
|
Fiorino G et al., 2017, Italy (PROSIT-BIO cohort) |
N = 97 n = 53 CD n = 44 UC |
Switch to CT-P13 |
6.1 ± 2.2 months (mean ± SD) |
Kaplan–Meier estimate for the probability of response: 94.5% at 8 weeks, 90.8% at 16 weeks, 78.9% at 24 weeks |
N/A |
Kaplan–Meier estimate for the probability of treatment persistence: 100% at 8 weeks, 98.7% at 16 weeks, 92.1% at 24 weeks |
N/A |
SAEs in 12.4% of patients; discontinuation due to SAEs in 3.1% IRRs in 7.2% of patients; discontinuation due to IRRs in 2.1% |
| Guerrero Puente L et al., 2017, Spain |
N = 36 n = 23 CD n = 13 UC |
Switch to CT-P13 |
8.4 ± 3.5 months (mean ± SD) |
Loss of response: 13.9% (mean time to relapse = 2.4 months); Relapse-free survival at 6 months: 85.7% |
Increased disease activity as assessed by the clinic, radiology, laboratory and endoscopy findings | N/A | No significant difference in pre- and post-switch drug levels at 8 and 16 weeks of follow-up |
3 (8.3%) of patients experienced AEs; 1 resulted in treatment discontinuation No IRR, malignancy or death |
| Kolar M et al., 2017, Czech Republic |
N = 74 n = 56 CD n = 18 UC |
Switch to CT-P13 | 56 weeks | Sustained remission rates: 72.2% at baseline, 77.8% at week 56 (p = 0.55) | Maintenance of HBI ≤ 4 in CD patients and PM < 2 in UC patients | N/A | ADA positive patients: 9.5% at baseline, 6.0% at week 56 | 2 patients with CD discontinued due to AEs |
| Ratnakumaran R et al., 2017, UK |
N = 210 n = 140 CD n = 48 FCD n = 18 UC n = 4 IBD-u |
Switch to CT-P13 (n = 191) Maintenance on IFX (n = 19) |
1 year |
Loss of response: Switch: 24.6% IFX: 42.1% (p = 0.10); Sustained remission rate: Switch: 58.1% IFX: 47.4% (p = 0.37) |
Increased disease activity according to physician’s global assessment. Asymptomatic patients in clinical assessment were considered in remission | N/A | N/A | Incidence of AEs were 0% for the IFX group and 4.7% for the switch group (p = 1.0) |
| Razanskaite V et al., 2017, UK |
N = 143 n = 118 CD n = 23 UC n = 2 IBD-u |
Switch to CT-P13 | Up to 1 year | IBD-Control-8 Score: 11 at switch, 14 at 3rd infusion (p = 0.041) | N/A | 27% at 1 year |
Mean ADA levels: Pre: 73.2 ± 83.9 AU/mL Post: 96.1 ± 102.0 AU/mL (p = 0.24); no significant difference in pre- and post-switch trough level |
The most common AEs at 3rd infusion were headaches (17%), joint pain (13.8%) and infections (13.8%) |
| Smits LJT et al., 2017, The Netherlands |
N = 83 n = 57 CD n = 24 UC n = 2 IBD-u |
Switch to CT-P13 | 52 weeks | Sustained remission rates: 64% at baseline, 73% at week 52 | Maintenance of HBI ≤ 4 in CD patients and SCCAI ≤ 3 in UC patients | 18% | 2 developed ADAs after switch; trough levels unaffected by switch | 7% (6) discontinued due to AEs |
| Sieczkowska J et al. 2016, Poland |
N = 39 (pediatric) n = 32 CD n = 7 UC |
Switch to CT-P13 |
CD: 8 ± 2.6 months (mean ± SD) UC: 5 ± 3.6 months (mean ± SD) |
Loss of response: CD: 6.3% UC: 14.2%; Sustained remission rate CD : 69% at baseline, 88% at last infusion |
N/A |
CD: 37% UC: 43% |
N/A |
2 IRRs after switch, 1 resulting in treatment discontinuation 1 UC patient discontinued due to varicella zoster infection after 1st CT-P13 infusion CT-P13 safety profile consistent with IFX |
|
Sustained remission rate UC : 29% at baseline, 57% at last infusion Mean PCDAI (range): At switch: 8.8 (0–35) 32 weeks: 6.6 (0–43); Mean PUCAI (range): At switch: 16.4 (0–30) 4th infusion: 2 (0–5) |
Maintenance of PCDAI < 10 or < 7.5 without the “height” item in CD patients and PUCAI < 10 in UC patients | |||||||
| Smits LJT et al., 2016, The Netherlands |
N = 83 n = 57 CD n = 24 UC n = 2 IBD-u |
Switch to CT-P13 | 16 weeks |
Sustained remission rate: CD: 60% at baseline, 67% at week 16 UC: 73% at baseline, 62% at week 16 |
Maintenance of HBI ≤ 4 in CD patients and SCCAI ≤ 3 in UC patients. | 6% | Median trough level: 3.5 μg/ml (range 0–18) at baseline, 4.2 μg/ml (range 0–21) at week 16 (p = 0.010); 2 developed ADAs post-switch | No SAEs |
| Jung YS et al., 2015, Republic of Korea |
N = 36 n = 27 CD n = 9 UC |
Switch to CT-P13 | 54 weeks |
Loss of response: CD: 7.4% UC: 11.1% |
Response in CD patients: ≥ 70-point CDAI decrease from baseline and ≥ 25% reduction in total CDAI score; Response in UC patients: 3-point decrease in total Mayo score or 2-point decrease in PM, along with 1-point decrease in rectal bleeding subscore or absolute rectal bleeding subscore ≤ 1 |
13.9% | N/A | 1 discontinued due to AEs |
| Kang YS et al., 2015, Republic of Korea |
N = 9 n = 5 CD n = 4 UC |
Switch to CT-P13 | 8 weeks |
Loss of response: CD: 20% UC: 0% |
Response in CD patients: > 70-point decrease in CDAI Response in UC patients: > 30% decrease in Mayo score, along with decreased rectal bleeding and endoscopy subscore |
N/A | N/A | 1 discontinued due to AEs |
| Park SH et al., 2015, Republic of Korea |
N = 60 n = 40 CD n = 4 FCD n = 16 UC |
Switch to CT-P13 | 30 weeks |
Disease worsening: CD: 12.9% FCD: 25% UC: 0%; |
N/A | N/A | N/A | 11.7% of patients receiving 5 mg/kg dose had a TEAE; 6.7% receiving > 5 mg/kg had a TEAE |
|
Sustained remission rate: CD: 80.6% FCD: 50% UC: 45.5% |
Maintained absence of draining fistulas in CD patients and as a total PM ≤ 2 in UC patients, with no individual subscore > 1 |
ADA antidrug antibodies, AE adverse event, CD Crohn’s disease, CDAI Crohn’s disease activity index, FCD fistulizing Crohn’s disease, HBI Harvey-Bradshaw Index, IBD inflammatory bowel disease, IBD-u unclassified inflammatory bowel disease, IFX infliximab originator, IRR infusion-related reaction, N/A not available, PCDAI Pediatric Crohn’s disease activity index, PM partial Mayo score, PUCAI pediatric ulcerative colitis activity index, SAE severe adverse event, SD standard deviation, SCCAI simple clinical colitis activity index, TEAE treatment-emergent adverse event, UC ulcerative colitis