Infliximab biosimilars: real-world and switching evidence

Infliximab continuation 94.9% in the switch group and 90.1% in the originator group (p=0.18); discontinuation for loss of response 4.9% vs 4.0%, immunogenicity 0.8% vs 1.0%, adverse effect 2.3% vs 1.0%; no differences in safety or efficacy between patients switched to CT-P13 or SB2.

Disease worsening in 11.6% of the switched group and 16.8% of the maintenance group; adjusted risk difference 5.9% (95% CI -1.1 to 12.9); adverse events, anti-drug antibodies and disease measures comparable.

Retention 85% (221 of 260) at the third biosimilar infusion; 59 patients (23%) discontinued by the last visit, 47 of them for perceived inefficacy; no serious adverse events; no change in objective disease activity or trough levels; BASDAI rose from 2.94 to 3.18 in axial spondyloarthritis (p=0.046); originator re-established in 47 of the 59 (80%).

ACR20 between weeks 54 and 78 ranged from 63.5% to 72.3% after the switch, 66.3% to 69.4% on continued reference and 65.6% to 68.3% on continued SB2; treatment-emergent adverse events 36.2%, 35.6% and 40.3%; infusion reactions 3.2%, 2.0% and 3.5%; new anti-drug antibodies in 14.6%, 14.9% and 14.1% of previously negative patients; 92.5% to 95.0% completed the transition period.

Geometric mean ratio of serum infliximab concentration after the switch to before it was 110.1% (90% CI 96.0 to 126.3) in ulcerative colitis and 107.6% (97.4 to 118.8) in Crohn disease, meeting the non-inferiority criterion.

97% remained on the medication throughout follow-up; a low number of adverse events; no change in disease activity, CRP, haemoglobin, faecal calprotectin, infliximab dose and interval or infliximab level; three patients developed new detectable anti-drug antibodies.

Disease worsening in 30% of the switched group and 26% of the group kept on originator, within the prespecified 15% non-inferiority margin; not powered for individual diseases.

ASAS20 at week 102 76.9% in the switched group and 80.7% in the maintenance group; ASAS40 and partial remission similar; anti-drug antibodies 27.4% vs 23.3%; discontinuation for adverse events 4.8% vs 3.3%.

ACR20 at week 102 71.8% in the switched group and 71.7% in the maintenance group; ACR50 51.4% vs 48.0%; anti-drug antibodies 44.8% vs 40.3%; adverse events in 53.8% vs 53.5%.

90.6% remained on infliximab; number of switches not associated with persistence after adjustment; clinical, CRP and faecal calprotectin remission comparable at baseline, week 12 and week 24.

Steroid-free clinical remission at 12 months in 76.9% (double switch), 65.7% (biosimilar to biosimilar) and 76.9% (single switch); treatment persistence 85.0%, 87.0% and 70.1%; no significant differences in clinical, CRP or calprotectin remission or persistence; infusion reactions in 3 of 176 (1.7%), all with anti-drug antibodies; no new anti-drug antibodies in the double-switch group, 3.8% and 3.7% in the other two.

One-year retention on GP1111 83% in originator-naive and 92% in originator-experienced patients; changes in disease activity before and after the switch close to zero; lower disease activity associated with higher retention.

No adverse effect on disease control or infliximab trough levels after a first or a second switch.

Drug persistence 94.9% at 54 weeks; loss of response in 17 (10.8%), 10 of them managed by dose optimisation; no change in clinical activity, fatigue, biological activity or pharmacokinetics; steroid-free remission maintained in 92.0% of double-switch and 90.0% of single-switch patients; beliefs about medicines unchanged.

No significant differences in physician-assessed disease activity, patient-reported outcomes, laboratory values or pre-infusion drug levels after the switch; new anti-drug antibodies in two patients; 12 of 48 had a significant relapse (7) or adverse event (5) within two years and 10 of them stopped Remsima.

Remission maintained at 12 months in 69.8% of Crohn disease patients (37 of 53) and 81.0% of ulcerative colitis patients (17 of 21); adverse events in 11 of 98 (11.2%).

Median trough level 5.5 mg/L before and after the switch in the whole group (p=0.05) and unchanged in Crohn disease (5.75 to 6.5 mg/L, p=0.68); in ulcerative colitis the median fell from 5.2 to 4.25 mg/L (p=0.019); two patients developed anti-drug antibodies; no change in disease activity and no safety concerns.

In the switch subgroup the efficacy estimates were 94.5%, 90.8% and 78.9% after 8, 16 and 24 weeks, against 95.7%, 86.4% and 73.7% in naive patients (log-rank p=0.64); across the cohort 66 serious adverse events after 2,061 infusions (12.1%), 38 of them infusion reactions; the biosimilar was stopped for severe infusion reactions in 29 patients, 2 of them in the switch group.

Disease activity similar 3 months before and after the switch; crude 1-year retention 84.1% vs 86.2% in the historic cohort (p=0.22), adjusted 83.4% vs 86.8% (p=0.03); 132 withdrew, mainly for lack of effect (54%) or adverse events (28%).

Similar incidence of side effects before and after; no clinically significant change in CRP, albumin, haemoglobin, platelets or white cells; IBD-control-8 score improved from 10.4 to 11.2; no difference in drug persistence between biosimilar and originator; no increase in immunogenicity; drug costs fell by 40,000 to 60,000 pounds a month.

Disease activity (Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index) and inflammatory markers (CRP, faecal calprotectin) did not change significantly over one year; anti-drug antibodies detectable in 7 of 83 (8%), five of them already present before the switch.

Median change in disease activity 0 for Crohn disease (range -23 to +7) and 0 for ulcerative colitis (range -3 to +6); median CRP and faecal calprotectin did not change significantly; median trough level rose from 3.5 to 4.2 ug/mL (p=0.010); two patients developed new anti-drug antibodies; five discontinued CT-P13; no serious adverse events.