Abstract Background Emerging evidence suggests early initiation of advanced therapies (AT) may improve outcomes, but optimal timing remains unclear. We aimed to assess the impact of AT timing on persistence. Methods We interrogated the Persistence Australian National IBD Cohort (PANIC5) registry from 2017-2021, covering all Australian AT prescribing data for Crohn’s disease (CD) and ulcerative colitis (UC). We included bio-naïve patients who initiated ATs after 2017, when all ATs became available. We defined early AT as 12 months from initial IBD treatment (aminosalicylates or thiopurines) and non-persistence as 6 months without dispensing. Persistence was compared using log-rank tests and Cox proportional hazards. Results 19,087 CD and 9,671 UC patients underwent 31,967 and 14,784 lines of AT respectively, totaling 103,025 patient-years follow up. Of this population, there were 11,097 CD and 8,018 UC bio-naïve patients who initiated ATs after 2017. Median time from initial treatment to AT was 36.0 (IQR 0.0-119.0) and 47.0 (14.0-115.0) months for CD and UC. 34.8% of CD and 22.1% of UC patients had early AT. In CD, early tumour necrosis factor inhibitor (TNFi) was associated with increased persistence (median 60.0 vs 44.0 months, HR = 0.90 95%CI:0.83-0.98, P=0.01). Early vedolizumab (HR = 1.45 95%CI:1.05-1.77, P=0.003) and ustekinumab were associated with decreased persistence (HR = 1.41 95%CI:1.16-1.72, P=0.001). In UC, early AT was associated with decreased persistence for TNFi (19.0 vs 31.0 months, HR = 1.26 95%CI:1.15-1.38, P0.001) and vedolizumab (40.0 vs 59 months; HR = 1.57 95%CI:1.30-1.89, P0.001). There was no difference between early or late tofacitinib (median 8months, HR = 1.63 95%CI:0.34-7.87 P=0.53). Subgroup analysis of patients without induction steroids found similar patterns for both CD (TNFi HR = 0.90, P=0.015; vedolizumab HR = 1.55, P=0.001; ustekinumab HR = 1.45, P=0.001) and UC (TNFi HR = 1.33, P0.001; vedolizumab HR = 1.54, P0.001; tofacitinib HR = 2.22, P=0.32). Conclusion Early AT is associated with increased persistence for TNFi in CD, suggesting timely treatment may improve outcomes. This was not true for other ATs in CD or in UC, even after adjusting for steroid use as a surrogate of disease severity. Conflict of interest: Dr. Gu, Bonita: Dr Bonita Gu has received sponsorship for conference attendance from Johnson & Johnson and Ferring. Chetwood, John: JDC has received speaker fees from Novartis, Falk, Johnson & Johnson, and Eli Lilly. Pudipeddi, Aviv: Aviv Pudipeddi has received speaker honoraria or advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Johnson & Johnson, Pfizer and Takeda. Yau, Yunki: No conflict of interest Kariyawasam, Viraj: Educational grants or research support – Ferring, Janssen, AbbVie, Takeda, Shire, WSLHD Research and Education network, Crohn’s and Colitis USA Speaker fees – Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Chiesi, Celltrion, GSK, Eli-Lilly, Research Review, Limbic Advisory boards – Janssen, Takeda, Ferring, AbbVie Board director- IBD Sydney organisation (not for profit) Paramsothy, Sudarshan: SP has served as a consultant for Vedanta Biosciences and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer
Gu et al. (Thu,) studied this question.