Introduction

Microscopic colitis (MC) is a chronic disabling inflammatory disease. Yet, the economic impact of MC is still largely unknown. In this nationwide study, we investigated societal costs, comprised of healthcare costs and productivity losses, in relation to MC diagnosis.

Aims & Methods

We identified 8,659 biopsy-verified patients diagnosed with MC between 2008 and 2017. Patients were followed from 4 years before diagnosis until either 4 years after diagnosis, emigration, death, or 2019 (end of follow-up), whichever came first. Each patient was compared to up to 5 general-population comparators matched on birthyear, sex, county of residence, and calendar year. Using real-world data from Swedish national registers, we determined healthcare costs from prescribed medications, non-primary outpatient visits, and hospitalizations, while costs for productivity losses were derived from lost workdays due to sick leave or disability leave. All costs were adjusted for inflation and converted from Swedish currency, SEK, to USD (1 USD = 10.61 SEK).

Results

Patients with MC had 1.54 times higher societal costs than their general-population comparators already at 4 years before diagnosis, and the excess cost further increased during the years leading up to diagnosis. The excess cost of MC peaked during the year of diagnosis when patients with MC had 2.11 times the cost of comparators, corresponding to a mean annual excess cost of $6,402 (adj. mean difference [95%CI]: $6,460 [$6,099; $6,820]).

Although the mean cost of MC decreased after diagnosis, it did not return to pre-diagnostic levels. Instead, the cost of MC persisted at 1.85 times the costs of their comparators 4 years after diagnosis. The absolute excess cost of MC was also significantly higher 4 years after diagnosis compared with 4 years before diagnosis ($4,654 vs $2,926; P-value <0.05). Stratification by age, sex, and education level showed similar cost trajectories, with cost ratios peaking in the year of diagnosis and persisting at higher levels after diagnosis.

While work loss was the largest contributor to the absolute excess cost of MC both before and after diagnosis, the cost ratio (1.83) was lower than for other cost categories. Compared with the general population, the relative excess cost was highest for outpatient visits with a cost ratio of 3.00 during the year of diagnosis, followed by 2.54 for medications and 2.36 for hospitalizations.

Table 1. Mean societal costs of patients with microscopic colitis (MC) and general-population comparators (control) in relation to year of diagnosis.

Conclusion

Patients with MC have higher societal costs than the general population before diagnosis, and the excess costs increase and persist for several years after diagnosis. While excess costs may be multifactorial, improved disease control could provide opportunities to reduce the post-diagnostic cost of MC.

Disclosure

The authors report no conflicts of interest related to this abstract.

Introduction

Risankizumab (RZB) is a highly specific humanized monoclonal antibody that targets the p19 subunit of interleukin-23 and was designed to have low immunogenicity and high bioavailability, allowing for less-frequent dosing, although the clinical implications of these modifications have not been studied. The FORTIFY maintenance open label extension (OLE) is an ongoing phase 3 substudy evaluating the long-term efficacy and safety of RZB in pts with moderate to severe Crohn’s disease (CD). Here, we report interim efficacy and safety results from the FORTIFY OLE following up to 4 years (yrs) of RZB treatment.

Aims & Methods

The FORTIFY (NCT03105102) OLE enrolled pts who completed 52 weeks (wks) of RZB maintenance.^1,2 Pts received subcutaneous (SC) RZB 180mg every 8wks (Q8w) starting at wk56, except for pts who received rescue therapy prior to or during the OLE; these pts received SC RZB 360mg Q8w (see Table footnote for rescue therapy details). Pooled data (180mg+360mg) were analyzed through wk144 of the OLE (wk200 of cumulative RZB treatment) using as observed (AO) and modified nonresponder imputation (mNRI, pts were considered nonresponders for visits after premature discontinuation of RZB due to the primary reason of lack of efficacy or adverse event limited to Crohn’s disease only, as well as initiation of rescue, while other missing data were handled by multiple imputation [MI]) methods (‘All Patients [No Rescue or Prior to Rescue]’ group in Table). For pts who received rescue therapy, only their data obtained prior to receiving rescue were included in the aforementioned AO and mNRI analyses (‘All Patients [No Rescue]’ group in Table). Data from pts on the day of or after rescue were analyzed separately and reported AO starting at the initiation of rescue (defined as the last nonmissing value prior to or on initiation of rescue) and every 24 wks post-rescue (‘Rescue’ group in Table). Safety was evaluated in all pts receiving any RZB treatment in the OLE. Treatment-emergent adverse events (TEAEs) reported on/after the first dose in the OLE were summarized (cutoff date: 30DEC2024).

Results

A total of 1112 pts (excluding 36 pts who received RZB rescue at entry to OLE) received ≥1 dose of RZB 180mg or 360mg in the OLE. Efficacy rates (per mNRI analysis) were stable from OLE wk0 to wk144 for clinical remission per stool frequency/abdominal pain score (SF/APS, 64.5% to 75.8%) and per CD Activity Index (CDAI, 68.6% to 82.8%), endoscopic response (55.1% to 73.8%), and endoscopic remission (39.0% to 58.8%) (Table). Pts who received rescue therapy in the OLE demonstrated clinical and endoscopic improvements over time. The profiles of TEAEs and AEs of special interest were consistent with the known safety profile of RZB.^3,4
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Conclusion

Durable clinical and endoscopic efficacy was observed in pts with moderate to severe CD who completed up to 4 yrs of RZB maintenance therapy in the FORTIFY OLE. Pts who received rescue therapy in the OLE also showed clinical and endoscopic improvements by wk144. No new safety risks for RZB were identified, supporting its long-term use in treating CD.

References

1. Ferrante M, et al. J Crohns Colitis. 2021;15(12):2001-2010.
2. Ferrante M, et al. Lancet. 2022; 399(10340):2031–46.
3. Papp KA, et al. J. Am. Acad. Dermatol. 2023; 89(6):1149–58.
4. Ferrante M, et al. J Crohns Colitis. 2024;18(Supplement_1):i168–70.

Disclosure

Marc Ferrante
Research grants from AbbVie, EG Pharma, Janssen, Pfizer, Takeda and Viatris. Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher. Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris
Remo Panaccione
Consulting fees from AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Theravance, UCB, and Takeda; speaker fees from AbbVie, Arena, Celgene, Ferring, Gilead Sciences, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; and research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. He has served on an advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Theravance
Jean-Frederic Colombel
Research grants from AbbVie, Janssen Pharmaceuticals, and Takeda; payment for lectures from AbbVie, Allergan, Amgen, Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Ferring Pharmaceuticals, Galmed Research, Genentech, GlaxoSmithKline, Imedex, Immunic, Iterative Scopes, Janssen Pharmaceuticals, Kaleido Biosciences, Lilly, Merck, Microbia, Novartis, PBM Capital, Pfizer, Protagonist Therapeutics, Sanofi, Takeda, TiGenix, and Vifor; and holds stock options in Intestinal Biotech Development.
Marla Dubinsky
Consulting fees from AbbVie, Arena, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead, Janssen, Pfizer, Prometheus Labs, and Takeda; and is founder and a shareholder of Trellus Health
Tadakazu Hisamatsu
Grant support from AbbVie, Daiichi-Sankyo, EA Pharma Co, Ltd. JIMRO, Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Co., Ltd. Consulting fees from EA Pharma Co, Ltd., Janssen Research & Development, LLC., Gilead Sciences, Eli Lilly, Bristol Myers Squibb. Lecture fees from AbbVie, EA Pharma Co, Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co, Ltd.
James O. Lindsay
Consultant and an advisory board participant for AbbVie, Atlantic Healthcare, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead, GSK, Janssen, MSD, Napp, Pfizer, Shire, Takeda, and Vifor Pharma; has received speaker fees and sponsorship for academic meetings from AbbVie, Ferring Pharmaceuticals, Janssen, MSD, Napp, Norgine, Pfizer, Shire, Tillotts Pharma, and Takeda; and has received investigator-led research grants from AbbVie, Gilead, Pfizer, Shire and Takeda.
Geert D’Haens
Consultant for AbbVie, AgomAb, AstraZeneca, AM Pharma, AMT, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals,, GSK, Pfizer, Immunic, J&J, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, Protagonist and Ventyx; and has received speakers bureau fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Pfizer, Bristol Myers Squibb, and Takeda

Alexandra Song, Yi Yao, Yang Yang, Javier Zambrano, Fernando Aponte, and W. Rachel Duan are full-time employees of AbbVie and may own AbbVie stock or options.

Funding
AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and authors thank all the trial investigators and the patients who participated in this clinical trial.
Medical writing support was provided by Stephanie Parsons, PhD, an employee of AbbVie.

Introduction

A wide range of relationships between the microbial community and various environmental or individual factors have been proposed. Monozygotic and dizygotic twins provide a unique model for assessing host-microbial interactions. The mycobiome has been increasingly implicated in the development of several diseases, but knowledge of the dynamics of the fungal community, particularly in twins, has not been addressed.

Aims & Methods

In this work, we investigated the fungal community in a twin cohort and explored its relationship with associated genetic and environmental factors through in-depth analysis.
The twin cohort consisted of 106 well-characterised and systematically studied monozygotic and dizygotic pairs (212 stool samples). DNA was extracted and PCR reactions were performed to sequence the lower gastrointestinal microbiome and the mycobiome community. The bacterial community was characterised using the V1-V2 region of the 16 rRNA gene and the fungal community was analysed using the ITS1-ITS2 region.

Results

The fungal community, represented by the sum of all fungal sequences, showed a significantly higher heterogeneity than the bacterial community. Several individual and genetic factors, such as the zygotic status of the twins (monozygotic vs. dizygotic), as well as sex, mode of birth, breast-feeding as newborns or living in the same household, were independent of the total number of fungal sequences. The bacterial community was significantly more abundant than the fungal community, the most common representatives of which were Candida and Geotrichum with sometimes very high abundances. Saccharomyces was also common in the cohort, but only in low abundance, other fungi with a wider distribution were Cladosporium or Penicillium. The environmental and individual factors mentioned above were also correlated with the individual fungal genera, but there were no significant correlations found here either. The next step was to correlate the bacterial and fungal communities with each other, and strong negative correlations were found with certain bacteria such as Prevotella.

Conclusion

Genetic factors in twins are not associated with dynamics in the faecal fungal community and were the subject of high inter-individual variability. However, there is a strong association between bacterial and mycobial interaction, which requires further in-depth understanding of microbial interactions.

Disclosure

No conflict of interest to declare