TABLE 3.
Discontinuation and Switching Outcomes of IFX Biosimilars
| Author, year | DC or retention rate a | DC causes a | Switch rate a | Reasons for Switch |
|---|---|---|---|---|
| Avouac, J 201818 | DC rate: overall (23%), RA (23%), AxSpA (27%), other rheumatic diseases (25%), Crohn’s (22%) | All indications: ineffectiveness (80%), AEs (8%), lost to follow-up (10%), pregnancy (2%) | All indications: Restart RP (79.7%) TNFi switch (8.5%) Switch to new MOA (3.4%) Biologic-free (8.5%) Mean time to switch, RP to biosimilar: overall 5.8 ± 4.9 years, RA 7.4 ± 5.5 years |
Setting: voluntary systematic switch to biosimilar |
| Bansback, N 202026 | All indications: Crude persistence: IFX-dyyb (80%), RP (75%); P = 0.02 Adjusted HR for persistence: 0.83 (vs RP); P = 0.07 |
All indications: 57.4% of biosimilar users had switched from RP | ||
| Boone, NW 201817 | Biosimilar discontinuation: RA (11%), AS (20%), IBD (7%) | RA (n = 1): ineffectiveness due to nocebo effect | Setting: nonmedical switch to biosimilar | |
| Codreanu, C 201833 | All indications: 13.2% discontinued biosimilar (CT-P13) | All indications: AEs (35%), ineffectiveness (25%), nonadherence (10%), patient request (10%), sponsor request (5%), lost to follow-up (15%) | ||
| Fisher, A 202034 | All indications: Policy cohort: 20.5% switch from RP to biosimilar Historical cohort: <5% switch from RP to another biologic |
Introduction of the British Columbia Ministry of Health Biosimilars Initiative (2019) | ||
| Glintborg, B 201727 | Overall 16% discontinued IFX biosimilar: RA (18.9%); PsA (13.3%); AxSpA (14.3%) All indications: HR for DC (vs RP): 1.31 [1.02-1.68]; P = 0.03 |
All indications: ineffectiveness (53.8%), AEs (28.0%), remission (3.8%), cancer (3.8%), death (1.5%), several reasons (2.3%), other reasons (eg, pregnancy, surgery; 6.1%), unknown (0.8%) | Time to switch, RA: 7.3 ± 3.6 years | Nationwide nonmedical switch to biosimilar (CT-P13) |
| Grøn, KL 201928 | RA-specific: Adjusted HR for discontinuation, 0-90 days (vs CZP): IFX biosimilar 0.58 [0.33-1.10] 91-365 days (vs CZP): IFX biosimilar 0.83 [0.59-1.17] Crude retention: IFX biosimilar (69%), CZP (60%), ABA (57%) Biosimilar: CT-P13 |
RA-specific:DC causes: Ineffectiveness (36-60%), AEs (15%-42%), otherb (<10%) | ||
| Kim, SC 201635 | All indications: 41% of biosimilar users switched from RP; proportion of biosimilar IFX increased by 19% from November 2012 to March 2014 |
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| Kim, TH 202036 | Overall 48.7% RA: overall 66.9%, naive 68.1%, switched 57.9% AS: overall 40.4%, naive 38.4%, switched 44.1% |
Overall ineffectiveness (40.6%), AEs (10.5%), loss to follow-up (14.6%), pregnancy (3.4%), drug holiday (14.6%), other (16.3%) RA overall: ineffectiveness (51.5%), AEs (11.7%), lost to follow-up (8.7%), pregnancy (3.9%), drug holiday (15.5%), other (8.7%) AS overall: ineffectiveness (32.4%), AEs (9.6%), loss to follow-up (19.1%), pregnancy (2.9%), drug holiday (14.0%), otherc (22.1%) |
12.3% (RA) and 35.0% (AS) switched from RP to biosimilar | Included patients who underwent nonmedical switch (CT-P13) and those who were biosimilar-naive |
| Layegh, Z 201937 | Overall Remsima DC: 13% | All indications: At 2-year follow-up: 1 patient on Remsima stopped because of AE (lung malignancy) After 2-year follow-up: 1 stopped because of AE (skin cancer) |
All indications: Overall switch rate (Remsima to another TNFi): 4% At 2-year follow-up: 2 patients receiving Remsima switched, both because of inefficacy; 3 patients switched back to RP After 2-year follow-up: 1 continued receiving RP; 1 switched to ABA because of ineffectiveness |
Setting: voluntary switch from Remicade to Remsima |
| Nikiphorou, E 201538 | DC rate: overall (28.2%), RA (26.7%), AS (21.4%), PsA (42.9%), JIA (50.0%), chronic reactive arthritis (0%) Biosimilar: CT-P13 |
RA-specific (n = 4): AE (antidrug antibodies) (75%), subjective reasons with no objective disease deterioration (25%) |
Switch rate, RA: 20% (n = 3) Among 3 patients who switched: 1 restarted RP, 1 switched to GLM, and 1 switched to RTX Mean time to switch, RA: 6.5 years |
|
| Nikiphorou, E 201939 | All indications: DC rate: RP (62%), biosimilar (30%) Biosimilar: CT-P13 |
All indications: DC reasons for new initiators, RP vs biosimilar: ineffectiveness (18.0% vs 5.0%), SE (9.1% vs 5.0%), antibodies (2.0% vs 5.0%), comorbidity (1.7% vs 1.0%), switch (to biosimilar per local policy or other: 24.0% vs 10.0%), remission (2.0% vs 1.0%), pregnancy (1.0% vs 1.0%), unknown (4.1% vs 2.0%) DC reasons for RP to biosimilar switchers: ineffectiveness (3.2%), SE (5.4%), antibodies (2.1%), comorbidity (1.1%), switch 6.5%, pregnancy (1.1%), unknown (4.3%) |
All indications: Switch rate: RP (24%) vs biosimilar 10%) |
|
| Sung, YK 201716 | RA-specific: DC rate (of entire observation period): RP (46.7%) vs biosimilar (43.6%) DC rate (before 6 months): overall (29%), RP (35.6%) vs biosimilar (23.6%) |
AEs: RP (37.5%), biosimilar (19.0%)Ineffectiveness was the most common reason in both groups but was only reported with RP | ||
| Tweehuysen, L 201840 | All indications: 24% discontinued biosimilar |
All indications: ineffectiveness (55%), AEs (23%), combination (21%) | Among 47 pooled patients who stopped CT-P13: 79% restarted RP, 15% switched to another biologic, and 6% did not use a biologic | Setting: voluntary open-label transition from RP to biosimilar (CT-P13) |
| Valido, A 201941 | All indications: After SW: 8.3% stopped therapy |
All indications: disease progression (5%), AEs (1.7%), lost to follow-up (1.7%) | Mean time to switch to biosimilar (range), RA: 8.0 (4.8-16.6) years Among 5 patients who stopped biosimilar, 1 patient restarted RP, 3 switched to new MOA, and 1 was lost to follow-up |
Setting: nonmedical switch from RP to biosimilar (CT-P13) (n = 60) |
| Vergara-Dangond, C 201742 | All indications: DC rate: 1 patient stopped because of AE (14.3%) |
1 patient stopped because of AE (14.3%) | Setting: 7 of 13 patients were switched to an IFX biosimilar (CT-P13) | |
| Yazici, Y 201815 | RA-specific: DC rated: 33.9% (RP continuers) vs 87.0% (RP to biosimilar switchers); P < 0.001 Mean time to discontinuation: 276 days (RP continuers) vs 132 days (RP to biosimilar switchers); P < 0.001 Biosimilar: CT-P13 |
RA-specific: Switch to another biologic during follow-up: 19.0% (RP continuers) vs 81.5% (RP to biosimilar switchers); P < 0.001 Among RP continuers who switched: 77.4% switched to another TNFi, 23.6% switched to a new MOA Among RP to biosimilar switchers: 88% restarted RP, 12% switched to another TNFi |
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| Yazici, Y 201814 | RA: DC rate: 42.1% (RP); 62.8% (biosimilar); P < 0.001 Time to switch: 263 days (RP) vs 207 days (biosimilar); P < 0.001 IBD: DC rate: 37.5% (RP); 62.3% (biosimilar); P < 0.001 Time to switch: 288 days (RP) vs 177 days (biosimilar); P < 0.001 Biosimilar: CT-P13 |
RA: Switch to another biologic: 23.5% (RP) vs 35.8% (biosimilar); P < 0.001 In the RP initiator cohort, patients switched to IFX biosimilar (34.8%) or other biologics (65.2%) In the biosimilar cohort, patients switched to RP (56.2%) or other biologics (43.8%) IBD: Switch to another biologic: 14.1% (RP) vs 50.6% (biosimilar); P < 0.001 RP initiators switched to biosimilar (46.5%) or other biologics (53.5%) The biosimilar cohort switched to RP (82.1%) or other biologics (17.9%) |
a Reported by author or data allowed for calculation.
b Cancer, plan for pregnancy, treated at another hospital, infection, lost to follow-up, death, surgery, project participation, remission, other, or unavailable.
c Change in therapy to IFX or other bDMARD, patient decision, investigator judgment, surgery, patient switched to another clinical study, improvement in symptoms, insurance criteria not fulfilled, trial ended.
d We noted discrepancy in discontinuation rate for switchers and reported data based on the Results section.
Ab = antibody; ABA = abatacept; AE = adverse effect; AS = ankylosing spondylitis; AxSpA = axial spondyloarthritis; Crohn’s = Crohn’s disease; CT-P13 = IFX biosimilar; CZP = certolizumab pegol; DC = discontinuation; ETN = etanercept; GLM = golimumab; HR = hazard ratio; IBD = inflammatory bowel disease; JIA = juvenile idiopathic arthritis; MOA = mechanism of action; PsA = psoriasis or psoriatic arthritis; RP = IFX reference product; RTX = rituximab; SE = side effect; TNFi = tumor necrosis factor inhibitor.