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PTH-076 Switching from originator infliximab to CT-P13: a UK single centre experience

2019· article· en· W3023753218 on OpenAlexaboutno aff
Anirudh Bhandare, Benjamin Crooks, Gaurav Nigam, Jimmy K. Limdi

Bibliographic record

Venuenot available
Typearticle
Languageen
FieldMedicine
TopicColorectal Cancer Treatments and Studies
Canadian institutionsnot available
Fundersnot available
KeywordsInfliximabMedicineComputer scienceInternal medicineTumor necrosis factor alpha

Abstract

fetched live from OpenAlex

Introduction and Aims The infliximab biosimilar (CT-P13) received market authorization for inflammatory bowel disease in late 2016 with the aim of reducing cost and increasing access to therapy. The prospect of ‘switching’ patients from originator to CT-P13 has concerned clinicians.We present an experience of ‘switching’ from originator infliximab (IFX-O) to CT-P13 and present efficacy, safety and immunogenicity data from our cohort. Methods We performed a retrospective review of patients switched from IFX-O to CT-P13 at our center. Disease demographics, clinical course and outcomes were analysed from electronic case records at 8 months and at last follow-up at 13 months. Results Ninety-six patients (35 female) were ‘switched’ from IFX-O to CT-P13. Of these 44 had Ulcerative colitis (UC) and 52 had Crohn’s disease (CD) with a mean age at diagnosis of 34.7 years (median= 33, IQR = 24.5). Montreal phenotype for UC was Proctitis( E1) = 1, Left sided(E2) = 16,Pancolitis ( E3) = 27 and for CD (L1 = 10,L2 = 12, L3 = 29,L4 = 1) and ( B1 = 27,B2 = 14, B3 = 11), 9 patients had perianal disease. Mean duration of IFX-O treatment before switching was 49.8 months (median = 44, IQR = 52) and on CT-P13 11.5 months (median 13). At switch, 76 patients had a normal CRP (UC = 33, CD = 43), and in 15 patients it was elevated (UC= 10, CD= 5). At 8 months, 72 patients (UC = 34, CD = 38) were in clinical remission (pMayo < 2 and HBI < 5) and 80 patients remained in biochemical remission (UC= 35,CD= 45). In 14 patients (UC= 8,CD= 6 ) CRP increased. Of 51 patients (UC= 21, CD= 30) undergoing endoscopic assessment, 31 achieved mucosal healing (UC =13, CD= 18). At 13 months 69 patients remained on CT-P13. 28% discontinued the drug due to immunogenicity(n=10), loss of response(n=5), surgery(n=5), remission (n=5), side effects (n=2) and 1 patient died of hospital acquired pneumonia. 39 out of 96 patients had therapeutic drug levels checked within a median of 13 months from switch. 27 had sub-therapeutic levels (below 4ug/ml ),11 of which were switched to another biologic, 5 referred for surgery, 4 had dose escalated to 10 mg/kg, 5 continued CT-P13( 4 with no antibodies seen and 1 with antibodies of 127),one had immunomodulator added and another stopped CT-P13 being in remission. Antibodies to Infliximab were seen in 15 of 39 patients (38.5%), of whom 8 were switched to an alternative biologic, 2 had dose escalation (10 mg/kg IFX),4 patients stopped IFX with no other intervention and 1 person continued treatment with low antibody titre of 6. Discussion Biosimilar IFX (CT-P13) was well tolerated. Clinical efficacy and loss of response rates with CT-P13 appears to be similar to IFX-O. This holds promise for a wider adoption of ‘switching’ to fulfil the purported aims of wider access to treatment at a lower cost.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.281
Teacher spread0.265 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2019
Admission routes1
Has abstractyes

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