Search

Background: In Germany, several biologic therapies are available for the treatment of moderate-to-severe plaque psoriasis, with the option of exceeding recommended dosages if standard dosing does not achieve a satisfactory treatment response., Objectives: To examine dose escalation in patients with biologic-treated psoriasis and its implications on the costs for German statutory health insurance (SHI)., Methods: We conducted a retrospective, noninterventional cohort study using German SHI health claims data from 2016 to 2021. Adult patients initiating biologic treatment were included in drug-specific cohorts. The odds for dose escalation, defined as the exceedance of the individually received daily dose over the maintenance dose recommended by the European product information, were compared between cohorts using multivariate logistic regression. The impact of dose escalation on SHI expenditure was analysed with a generalized linear model., Results: The relative frequency of dose escalation varied between cohorts [range 1%, < 5/92 (risankizumab) to 43%, < 5/7 (infliximab)]. Compared with patients treated with risankizumab, the odds for dose escalation were statistically significantly (P < 0.05) higher in patients treated with all other biologic drugs except tildrakizumab. Patients with dose escalation during the maintenance phase accrued on average €6473 more in direct healthcare costs to SHI over a 1-year period compared with those without dose escalation, with statistical significance (P < 0.05) after controlling for differences in covariates., Conclusions: Compared with patients treated with other biologics, dose escalation during the maintenance phase was lowest among patients treated with risankizumab. Dose escalation was associated with higher costs and thus a higher economic burden for German SHI., Competing Interests: Conflicts of interest A.P. is an employee of the Department of Dermatology of the University of Frankfurt, Germany. He has received lecture fees and advisory board fees from AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, BMS, Boehringer-Ingelheim, Celgene, Celltrion, GSK, Eli Lilly, Eva Pharma, Galderma, Hexal, Janssen, Klinge Pharma, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, Moonlake, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough, UCB Pharma and Zuellig Pharma. A.M.S. and S.G.R. are employees of AbbVie Inc. and may hold AbbVie stock, stock options and/or patents. AbbVie Inc. sponsored the study, contributed to the design, participated in the interpretation of data. K.C.M., V.W., A.M. and A.H. are employees of the IGES Institut GmbH, which is a paid consultant of AbbVie Inc. for designing the study, carrying out the analyses, and interpreting the results. P.L. is an employee of the InGef – Institute for Applied Health Research Berlin GmbH, which was contracted and reimbursed by IGES Institut GmbH for providing the data and carrying out the analyses. M.G.L. is an employee of the Icahn School of Medicine at Mount Sinai, New York, USA. He has received research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer-Ingelheim, Cara therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron and UCB, Inc., and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Aristea Therapeutics, Avotres Therapeutics, Brickell Biotech, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Celltrion, Corevitas, Dermavant Sciences, Dr. Reddy, EPI, Evommune, Inc., Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Galderma, Helsinn, Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, Strata, Trevi and Verrica., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: The Saudi Food and Drug Authority (SFDA) has approved the subcutaneous (SC) administration of infliximab, presenting a more convenient alternative with reduced outpatient visits and diminished expenses compared to the intravenous (IV) administration. However, the financial implications of this formulation have not been examined from the perspective of Saudi payers., Methods and Materials: A prevalence-based budget impact model was developed to evaluate the financial effects of introducing "environment without" versus "with infliximab SC." The model's time horizon spanned over 2 years (2021-2023), aligning with the biennial national pharmaceutical procurement cycle. The comparison focused on infliximab SC versus all available formulations of infliximab IV in the Saudi market for two inflammatory bowel diseases (IBD): Ulcerative Colitis (UC) and Crohn's Disease (CD). Treatment comparators' comparability and dose escalations were substantiated by published studies, utilizing dosing information from the summary of product characteristics. Drug acquisition costs were derived from SFDA registered prices, with IV formulation administration costs included. Scenario analysis assessed the budget impact of infliximab SC introduction at uptake rates ranging from 0% to 100%., Results: Introducing infliximab SC demonstrated cost-saving potential in the treatment of IBD. At 100% uptake with UC patients for 2 years, infliximab SC resulted in savings of -SAR-31.9 million (-SAR29,145 per patient). Similarly, for CD, introducing infliximab SC at 100% uptake over 2 years yielded savings of -SAR106.2 million (-SAR36,585 per patient)., Conclusion: This study reveals that infliximab SC is associated with cost-saving potential when compared to infliximab IV formulations available in Saudi Arabia. Future research should address uncertainties related to real-world comparative effectiveness, the convenience of administration, patient tolerability, and physician acceptance of the SC formulation of infliximab, alongside comparisons with other TNF-alpha inhibitors., Competing Interests: N Alkhatib holds equity in Pi Pharma Intelligence, LLC, which provides health technology solutions, scientific and consulting services to biopharmaceutical, diagnostics, and medical device companies on a nonexclusivity basis. By the company internal policy, owners, employees, and associates are prohibited from holding equity in client and sponsor organizations or contracting independently with client and sponsor organizations or receiving compensation independently from such organizations. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Alkhatib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy)., Design: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE)., Results: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively)., Conclusion: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal., Trial Registration Number: NCT00571337 and NCT02177071., Competing Interests: Competing interests: PB has received research grants from AbbVie, Amgen, Celltrion, Mylan, Pfizer and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly and Takeda; and consulting fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda and Tetrameros. LV has received fees from AbbVie, Amgen, Biogen, Mylan, Takeda, MSD, Janssen, Pfizer, Ferring and Galapagos. SV has received speaker’s fees from AbbVie, Ferring, Janssen and Takeda. J-FC has received grants from AbbVie, Janssen Pharmaceuticals, Prometheus, Takeda and Bristol Myers Squibb; receiving payment for lectures from AbbVie, and Takeda; receiving consulting fees from AbbVie, Amgen, AnaptysBio, Allergan, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Genentech (Roche), Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Invea, Iterative Scopes, Merck, Landos, Microba Life Science, Novartis, Otsuka Pharmaceutical, Pfizer, Protagonist Therapeutics, Prometheus, Sanofi, Seres, Takeda, Teva, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. EL has received educational and research grants from Janssen, Pfizer, AbbVie and Takeda, Fresenius-Kabi; speaker fees from AbbVie, Dr Falk Pharma, Ferring, Janssen, Pfizer, Celgene, Bristol Myers Squibb (BMS), Galapagos and Takeda; advisory board fees for AbbVie, Celgene, Ferring, Janssen, BMS, Pfizer, Takeda, Gilead-Galapagos, Arena and Elli Lilly; and consultancy fees from AbbVie., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Limited approval of second-line treatments in pediatric inflammatory bowel disease (pIBD) necessitates optimized use of infliximab (IFX) with proactive therapeutic drug monitoring (TDM). We investigated whether early combo-therapy with an immunomodulator (IMM) provides additional benefit., Methods: In the retrospectively reviewed medical records of all children treated with IFX and proactive TDM between 2013 and 2022, IMMearly (IMM ≤3 months since IFX start) was evaluated against IMMother/no (late/short or no IMM) over follow-up of 3 to 60 months. Kaplan-Meier analysis was used to analyze time to loss of response (LOR) with IFX discontinuation or time to antibodies-to-IFX (ATI) development., Results: Three hundred fifteen patients with pIBD were reviewed; of those, 127 with 2855 visits were included (77 CD, 50 UC/IBD-unclassified). Sixty patients received IMMearly, 20 patients IMMother, and 47 had IFX monotherapy. Median follow-up time was 30 and 26 months for IMMearly and IMMother/no, respectively, with comparable proactive TDM. Infliximab treatment persistence was 68% after 60 months. Loss of response was observed in 7 IMMearly and 15 IMMother/no patients (P = .16). Early combo-therapy significantly delayed LOR with IFX discontinuation (median LOR free interval IMMearly 30 months vs IMMother/no 9 months, P = .01). Patients with IMMother/no were 10-, 3- and 2-times more likely to experience LOR with IFX discontinuation after 1, 3, and 5 years, respectively. There were no significant group differences regarding the presence of any positive (>10 arbitrary units per milliliter [AU/mL]) or high (>100 AU/mL) ATI, median ATI concentrations, and ATI-free interval., Conclusions: Early IMM combo-therapy in proactively monitored patients with pIBD significantly prolonged the median LOR free interval compared with late/short or no IMM treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cyclophosphamide and infliximab are recommended as induction therapies for severe Behçet's syndrome. Whether infliximab is safer and more effective than cyclophosphamide in treating severe Behçet's syndrome is not known., Methods: In this phase 2, Bayesian, multicenter randomized controlled trial, we assigned patients fulfilling the International Study Group's criteria for Behçet's syndrome who had major vascular or central nervous system involvement to receive either intravenous infliximab (5 mg/kg at weeks 0, 2, 6, 12, and 18) or cyclophosphamide (0.7 g/m 2 intravenously at weeks 0, 4, 8, 12, 16, and 20, with a maximal dose of 1.2 g/infusion). All patients received the same glucocorticoid regimen. The primary outcome was complete response (clinical, biological, and radiological remission with a daily prednisone dose ≤0.1 mg/kg) at week 22., Results: Between May 2018 and April 2021, 52 patients with severe Behçet's syndrome (n=37 [71%] with vascular Behçet's syndrome and n=15 [29%] with neuro-Behçet's syndrome) were randomly assigned to receive either infliximab or cyclophosphamide. Complete response was achieved by 22 out of 27 (81%) and 14 out of 25 (56%) patients in the infliximab and cyclophosphamide treatment groups, respectively (estimated difference, 29.8 percentage points; 95% credible interval, 6.6 to 51.7). The posterior probability that at least 70% of treated individuals achieved complete response by week 22 was 97.4% for infliximab and 6.0% for cyclophosphamide. Overall, adverse events were recorded in 8 out of 27 (29.6%) patients receiving infliximab and 16 out of 25 (64%) patients receiving cyclophosphamide (estimated difference, -32.3 percentage points; 95% credible interval, -55.2 to -6.6). Serious adverse events were reported in 15% and 12% of patients receiving infliximab and cyclophosphamide, respectively., Conclusions: Among patients with severe Behçet's syndrome, induction therapy with infliximab had a superior complete response rate at 22 weeks and fewer adverse events than induction with cyclophosphamide. (Funded by the French Ministry of Health.).

Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC., Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed., Findings: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study., Interpretation: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3., Funding: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag., Competing Interests: Declaration of interests MCC is supported by a Gandel Major Philanthropy Grant and an Australian Postgraduate Award, and has received research funding from Janssen-Cilag. CFDLWS has served as a speaker for DiaSorin, has received educational support from Pfizer, Shire, and Ferring, has received research funding from the Robert C Bulley Charitable Foundation and St Vincent's Hospital Melbourne Research Endowment Fund, and is supported by an Australian National Health and Medical Research Council (NHMRC) Postgraduate Scholarship. DC has received educational support from Viatris and is supported by an NHMRC Postgraduate Scholarship. EKW has served as a consultant, advisory board member, or speaker for AbbVie, Bristol Myers Squibb, Ferring, Janssen, Celltrion, Falk, and Takeda, is supported by an NHMRC Emerging Leadership Level 1 Fellowship, and has received research support from Ferring and Janssen. AP has served as an advisory board member or received speaker fees from AbbVie, Ferring, Janssen, Pfizer, Takeda, and Dr Falk Pharma. BC has served as a consultant, advisory board member, or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, the Helmsley Charitable Trust, the NHMRC, and Takeda. WN has received educational and research support from Pfizer, AbbVie, Janssen, Shire and Ferring. JB has served as a consultant, advisory board member, or speaker for AbbVie, Ferring, Janssen, Celltrion, Chiesi, Janssen, Pfizer, Amgen, GlaxoSmithKline, Bristol Myers Squibb, Microba, Anatara, and Takeda, and has received research support from the NHMRC, United States Department of Defense, AbbVie, Janssen, Ferring, Pfizer, and Takeda. MG has served on the advisory board of Pfizer and AbbVie and has received speaker fees and research grants from Abbvie, Celltrion, Janssen, Pfizer and travel grants from Pfizer. NM has received speaker fees from Takeda and Baxter, and educational support from Baxter. DRVL has received consulting fees from AbbVie and speaker fees for Takeda. NSD reports serving as an advisory board member or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, and the NHMRC. RWL reports advisory board membership for AbbVie, Aspen, Bristol Myers Squibb, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda, and research grants from the University of Sydney, the McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant, the Gastroenterological Society of Australia, the NHMRC, The Gutsy Group, and Pfizer. MPS has received educational grants or research support from Gilead and Celltrion, speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli Lilly, and Dr Falk Pharma, and has served on advisory boards or received consultancy fees for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, Bristol Myers Squibb, Celltrion, and Eli Lilly, and has received travel grants from Pfizer and Dr Falk Pharma. PDC has served as a consultant, advisory board member, or speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion and Emerge Health, and is supported by a NHMRC Emerging Leadership Level 2 Fellowship, and has received research support from AbbVie, Ferring, Janssen and Pfizer. All other authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Aims: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs., Methods: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes., Results: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10 -10 ) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months., Conclusion: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To study the safety and efficacy of intravitreal infliximab administered at the conclusion of pars plana vitrectomy (PPV) in the treatment of proliferative vitreoretinopathy (PVR) associated with rhegmatogenous retinal detachment (RRD)., Design: Randomized controlled phase II clinical trial., Subjects: Patients with primary RRD and grade C PVR, according to the updated Retina Society Classification., Methods: Sixty-six patients were randomized in a 1:1 ratio to undergo PPV and silicone oil (SO) injection with or without intravitreal injection of 1 mg/0.05 mL of infliximab in the air-filled globe before SO injection at PPV conclusion. Surgeons were masked to treatment allocation until PPV conclusion., Main Outcome Measures: The primary outcome measure was anatomic success (defined as complete retinal reattachment without a tamponade at 6 months post SO removal). Secondary outcome measures were final best-corrected visual acuity (BCVA), single-operation success rate (SOSR), rate of recurrent detachment, central macular thickness (CMT) by macular OCT, macular function by multifocal electroretinogram, and macular vascular density (VD) by OCT angiography., Results: Sixty eyes of 60 patients, 30 eyes in each group, completed the study. At baseline, there were no differences regarding age, gender, history of trauma, lens status, duration of RRD, BCVA, intraocular pressure (IOP), intraocular inflammation (IOI), detachment extent in clock hours, number/size of breaks, presence of vitreous hemorrhage, axial length, or grade/extent of PVR between both groups. For the outcome measures, 30 eyes in the infliximab group achieved anatomic success vs. 29 eyes in the control group. The SOSR was higher in the infliximab group (26) vs. the control (23), but this was not statistically significant (P = 0.317). Final logarithm of the minimum angle of resolution BCVA was better in the infliximab group (mean, 0.96; standard deviation [SD], 0.4; Snellen equivalent ≈ 20/180) vs. the control (mean, 1.14; SD, 0.4); Snellen equivalent ≈ 20/280; P = 0.044). There were no differences regarding IOP, IOI, time of SO removal, macular function, CMT, or VD., Conclusions: Pars plana vitrectomy with SO tamponade with or without intravitreal infliximab is effective in treating PVR-associated RRD. Infliximab may be associated with modest improvement in final visual outcomes but not anatomic outcomes., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Recently, a formula of subcutaneous infliximab (SC-IFX) has been approved for inflammatory bowel disease (IBD), demonstrating a better pharmacokinetic and immunogenic profiles, compared to intravenous infliximab (IV-IFX), with similar efficacy and safety., Aim: The aim of this study is to evaluate the clinical, biochemical, and pharmacological outcomes of IBD patients in clinical remission, who switched from IV-IFX to SC-IFX, with a follow-up period of 6 months., Methods: Retrospective cohort study, including IBD patients in clinical remission, previously medicated with IV-IFX, who switched to SC-IFX 120 mg every other week. Biochemical parameters were evaluated before the switch and 6 months after, namely infliximab serum concentrations, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin., Results: Included 41 patients in clinical remission, 32 with Crohn's disease (78.0%) and 9 with ulcerative colitis (22.0%). All patients maintained clinical remission during the 6 months after the switch, with a treatment persistence rate of 100%, and no patients requiring corticosteroid therapy, switching back to IV-IFX, or IBD-related hospitalization. The mean infliximab serum concentrations were significantly higher after 6 months of SC-IFX (17.3 ± 6.6 vs. 9.1 ± 5.5 µg/ml, P  < 0.001). However, there were no differences between values of ESR, CRP, and fecal calprotectin, before and after the switch ( P  = 0.791, P  = 0.246, and P  = 0.639). Additionally, none of the patients developed antibodies to infliximab., Conclusion: Switching from IV-IFX to SC-IFX in IBD patients in clinical remission is effective and leads to higher infliximab serum concentrations, regardless of the combination with immunomodulatory therapy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Psoriasis is a chronic inflammatory disease that is debilitating, particularly in its more severe forms. Multiple systemic therapies are used in moderate-to-severe psoriasis, but the development of biological interventions has revolutionized its management and improved its outcomes. To compare the effectiveness and safety of the different biological interventions approved for use in moderate-to-severe plaque psoriasis. Multiple databases were searched for relevant articles and a prospectively planned network meta-analysis was conducted on randomized controlled trials that assessed biological treatments in moderate-to-severe psoriasis. The search yielded 84 trials that encompassed 39,798 patients. Infliximab 5 mg/kg had the highest probability of achieving 75% reduction on PASI scale in comparison to placebo (RR = 18.76, 95% CI [12.31; 28.57], high certainty), while Ixekizumab 80 mg and Brodalumab 210 mg had the highest probability at achieving PASI90 and PASI100 (37.81, [28.57; 50.03] and 81.04, [26.16; 251.01], respectively, with moderate certainty) On the other hand, Risankizumab 150 mg and Ustekinumab 90 mg were the only regimens with significantly less withdrawal rates due to adverse events (0.41, [0.18-0.96], and 0.57, [0.35-0.91], respectively with High certainty) compared to placebo. Anti-IL17 and Infliximab were among the most effective in ameliorating the symptoms of psoriasis, however, anti-IL17 were better at achieving full or almost full improvement on the PASI scale. Real life decision-making is not so clear-cut and should remain patient centered, taking into consideration factors such as safety, comorbidities, biologic naivety, dosing preferences and insurance considerations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Infliximab (IFX) has transformed the management of inflammatory bowel diseases (IBD). While intravenous (IV) IFX has been effective, a subcutaneous (SC) formulation offers advantages in convenience and cost. However, there is lack of evidence regarding the transition from IV to SC-IFX, especially for patients with inadequate responses. This study investigates the effectiveness of switching from IV to SC-IFX in patients with inadequate responses during IV maintenance therapy. A retrospective study enrolled IBD patients who transitioned to SC-IFX after demonstrating inadequate responses during IV maintenance therapy. The study collected data of demographics of patients and dose and therapies administered prior to the IV-IFX. Primary outcomes included improvements in C-reactive protein (CRP) or fecal calprotectin (FC) levels. This study evaluated the trough levels and its differences between pre- and post-switching. Among 44 patients included, 10 exhibited CRP elevation before the switch, with 6 showing normalization post-switch. Similarly, 42 patients had elevated FC levels pre-switch, with 26 experiencing reductions post-switch. Trough levels increased after the switch. However, there were no significant differences between responders and non-responders. This study is the first study to investigate the transition therapy of IV to SC-IFX in patients with inadequate response. This suggests that SC-IFX could be a viable alternative in the management of IBD. However, further research is necessary to evaluate its efficacy in a larger population of patients who exhibit inadequate responses during IV-IFX maintenance therapy., (© 2024. The Author(s).)

Background: The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD)., Methods: This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5., Results: This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5., Conclusions: This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria., Methods: We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk., Results: Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence., Conclusions: Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain., Protocol Registration: www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.

CT-P13, a biosimilar of infliximab, is used to treat inflammatory diseases that arise from immune system complications, resulting in excessive and persistent inflammation. The subcutaneous (SC) formulation of CT-P13 overcomes the drawback of prolonged administration associated with the intravenous (IV) infliximab biosimilar, necessitating autoinjector (AI) administration. This randomized, open-label, two-arm, parallel-group, single-dose clinical pharmacology study aimed to evaluate the pharmacokinetics (PK) and safety of CT-P13 SC administration via AI compared with the existing pre-filled syringe (PFS) method. A total of 147 healthy participants were randomized into two groups, of which 139 completed the study. Blood samples were collected from before CT-P13 SC administration to 2016 h after the start of the administration. Serum concentrations were analyzed using the Meso Scale Discovery electrochemiluminescence method. Geometric mean ratios (90% confidence interval) of the AUC inf (areas under the concentration-time curve from zero to infinity) and C max (The maximum serum concentration) for CT-P13 SC AI versus CT-P13 SC PFS groups, were 94.15% (85.02%-104.26%), 92.48% (84.66%-101.01%), respectively. CT-P13 SC AI and CT-P13 SC PFS achieved comparable PK because the 90% CI was within the predefined equivalence margin. At the end of the study, immunogenicity results revealed that 70 (97.22%) and 73 (98.65%) participants tested positive for anti-drug antibody (ADA) in the CT-P13 SC AI and CT-P13 SC PFS groups, respectively. They were tested positive for neutralizing antibodies. No other significant safety differences were observed between the treatment groups. In conclusion, both administrations demonstrated PK equivalence and were both safe and well-tolerated., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: The aim of this study was to evaluate the influence of anti-infliximab (IFX) antibodies on three different points of care: response/tolerance to IFX, tapering strategy, and in a subsequent treatment with a second tumor necrosis factor inhibitor (TNFi)., Methods: A prospective cohort of 60 patients with radiographic axial spondyloarthritis who received IFX were evaluated retrospectively regarding clinical/laboratorial data, IFX levels, and anti-IFX antibodies at baseline, after 6, 12 to 14, 22 to 24, 48 to 54, 96 to 102 weeks, and before tapering or switching., Results: Anti-IFX antibodies were detected in 27 patients (45%), of whom 23 (85.1%) became positive in the first year of IFX treatment. In comparison to the group that was negative for anti-IFX antibodies, patients who were positive for anti-IFX antibodies demonstrated the following: less use of methotrexate as a concomitant treatment to IFX (5 [18.5%] vs 14 [42.4%]; P = 0.048), more infusion reactions at 22 to 24 weeks (P = 0.020) and 48 to 54 weeks (P = 0.034), more treatment failures (P = 0.028) at 48 to 54 weeks, reduced overall IFX survival (P < 0.001), and lower sustained responses (P = 0.044). Of note, patients who were positive for anti-IFX antibodies exhibited a shorter tapering survival (9.9 months [95% confidence interval (CI) 4.0-15.8] vs 63.4 months [95% CI 27.9-98.8]; P = 0.004) in comparison with patients who were negative for anti-IFX antibodies. Conversely, for patients who failed IFX, patients who were positive for anti-IFX antibodies had better clinical response to the second TNFi at three months (15 [83.3%] vs 3 [27.3%]; P = 0.005) and six months (15 [83.3%] vs 4 [36.4%]; P = 0.017) than the patients who were negative for anti-IFX antibodies after switching., Conclusion: This study provided novel data that anti-IFX antibodies is a parameter for reduced tapering survival, reinforcing its detection to guide clinical decision. Additionally, we confirmed in a long-term cohort the anti-IFX antibody association with worse IFX performance and as predictor of the second TNFi good clinical response., (© 2024 American College of Rheumatology.)

Objectives: Combination therapy consists of both anti-tumor necrosis factor (anti-TNF) and an immunomodulator (IMM) and has been shown to improve outcomes in patients with inflammatory bowel disease (IBD). This study assesses the impacts of IMM withdrawal from combination therapy to anti-TNF monotherapy in children with IBD., Methods: This single-center retrospective cohort study included children with IBD initiated on combination therapy between 2014 and 2019 who discontinued the IMM. We evaluated whether IMM withdrawal impacts laboratory values and disease activity. Linear mixed effects models with random intercepts were used to compare differences between groups. Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation of therapy., Results: One hundred and fifty-two patients discontinued the IMM which did not significantly affect disease activity. However, 18% of patients escalated therapy after IMM withdrawal, primarily due to low anti-TNF levels. Lower anti-TNF and higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels before IMM withdrawal were associated with subsequent escalation of therapy. Overall, there was no statistically significant effect on anti-TNF drug levels. Patients with Crohn's disease (CD) on infliximab (IFX) and methotrexate (MTX) who discontinued the IMM had an increase in mean ESR and CRP (p < 0.05)., Conclusions: IMM withdrawal from anti-TNF combination therapy may be considered safe in the setting of higher anti-TNF levels and normal serum inflammatory markers. Clinicians should consider assessing anti-TNF levels and inflammatory markers after IMM withdrawal, especially in patients with CD receiving IFX who discontinued MTX., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Inflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn's Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD., Aim: This study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD., Method: This study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn's Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period., Results: In the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002)., Conclusion: Both IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients., Clinical Trial Registration: This study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022)., (© 2024. The Author(s).)

Background & Aims: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC)., Methods: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population)., Results: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified., Conclusions: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction., Clinicaltrials: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to evaluate the efficacy and safety of infliximab (IFX) in patients with parenchymal neuro-Behçet's syndrome (p-NBS)., Methods: We retrospectively analysed eleven p-NBS patients treated with IFX at our institution and combined them with studies from database searches for a meta-analysis. Pooled estimates of clinical response (complete and partial remission) and MRI improvement at months 3, 6, and 12 were calculated., Results: One patient achieved CR and the other ten patients achieved PR at our institution. 8 studies (77 patients) were included in the meta-analysis. At 3, 6, and 12 months, 97% (95%CI 61.9-100%), 89.6% (95%CI 45.9-100%), 100% (95%CI 96.0-100%) of patients showed clinical response and 100% (95%CI 89.7-100%), 89.1% (95% CI 26.3-100%), 99.5% (95% CI 96.0-100%) of patients showed radiological improvement, respectively. Severe adverse events were observed in 7 patients., Conclusions: IFX was effective and relatively safe for p-NBS. Patients should be re-evaluated after 3 months of IFX to determine further therapy.

Background & Aims: Biologic therapies may effectively treat Crohn's disease (CD), and pediatric patients who discontinue multiple biologics risk exhausting treatment options. The frequency and context of biologic discontinuation have not been well-characterized. We aimed to determine patterns of biologic use, discontinuation, and evaluation in pediatric patients with CD., Methods: Pediatric patients with CD at 7 U.S. centers (2010-2020) were identified. Prospective ImproveCareNow registry data were supplemented with medical record abstraction. Biologics included monoclonal antibody and small molecule medications. Therapeutic drug monitoring (TDM) was considered induction if <14 weeks after biologic start, proactive if later during quiescent disease, and reactive during active disease., Results: Of 823 patients included (median age, 13.0 years; 40% female), 86% started biologics (78% infliximab, 21% adalimumab, <1% others). Twenty-six percent used concomitant immunomodulators for ≥12 months. Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive. Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%). If inefficacy, 86% underwent pre-discontinuation evaluation. If infliximab or adalimumab inefficacy and TDM was done, 62% had levels <10 μg/mL. Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation., Conclusions: Most children with CD are treated with biologics; 25%-37% discontinue biologics, resulting in 1 in 12 using >2 biologics during pediatric care. Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation. Concomitant immunomodulator use and proactive TDM decreased risk of biologic discontinuation. Strategies are needed to preserve biologic efficacy and prevent biologic discontinuation., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Acute severe ulcerative colitis (ASUC) is a potentially life-threatening medical emergency that occurs in up to 25% of patients with ulcerative colitis. Although intravenous corticosteroids remain the cornerstone of therapy, 30-40% of patients will not respond and need timely consideration of rescue therapy with (currently) either infliximab or ciclosporin or indeed colectomy, underscoring the importance of multidisciplinary care to ensure favourable outcomes for patients. We discuss the current evidence and present an approach to the management of ASUC for general and specialist clinicians caring for patients with ASUC., Sources of Data: The information in this review is derived from data published in peer- reviewed academic journals and registered clinical trials., Areas of Agreement: Management of acute severe colitis requires a multidisciplinary approach with early initiation with steroids and timely escalation of treatment to either medical rescue therapy or surgery., Areas of Controversy: Balancing the risks of delayed surgery vs. optimizing medical therapy, including accelerated dosing schedules for biologics, remains ambiguous., Growing Points: The position on newer molecules like Janus Kinase inhibitors, such as tofacitinib, is a growing area with early real-world data showing promise for steroid refractory ASUC., Areas Timely for Developing Research: Developing predictive biomarkers and clinical risk scores for personalized rescue therapy selection is an evolving area of research., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Immunogenicity is a major reason for secondary loss of response to infliximab (IFX). Recent work suggested potentially lower immunogenicity of subcutaneous (SC) compared to intravenous (IV) IFX. However, it is unknown whether re-exposure to IFX SC after secondary loss of response and immunogenicity to its intravenous formulation is safe and effective., Methods: In a retrospective cohort study conducted at two medical centers, patients with clinically (Harvey-Bradshaw Index ≥ 5) and/or biochemically (fecal calprotectin > 250 µg/g) active Crohn's disease (CD) and previous immunogenic failure of IFX IV underwent exposure to IFX SC. Harvey-Bradshaw Index, fecal calprotectin, IFX serum concentration, and anti-drug antibodies were assessed until month 12., Results: Twenty CD patients were included. The majority of patients (90%) had previous treatment with three or more biologics. Fifteen (75%) and ten (50%) of 20 patients continued IFX SC treatment until months 6 and 12, respectively. No immediate hypersensitivity reactions were observed. Two patients discontinued IFX SC treatment because of delayed hypersensitivity at week 2 and week 4. IFX serum concentrations increased from baseline to month 12, while anti-drug antibody levels decreased. Combined clinical and biochemical remission at month 12 was observed in seven of 20 patients (35%)., Conclusion: Subcutaneous infliximab treatment of Crohn's disease patients with previous immunogenic failure of intravenous infliximab was well tolerated and effective in a cohort of patients with refractory Crohn's disease., (© 2024. The Author(s).)

Background: Subcutaneous [SC] infliximab may provide multiple benefits over intravenous [IV] formulations. However, studies for efficacy and safety in inflammatory bowel disease [IBD] have been constrained by small sizes that limit the interpretation of outcomes, particularly for subgroups potentially at high risk of disease relapse., Methods: We conducted a systematic review and random-effects meta-analysis up to January 2023, to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis., Results: We identified 15 studies of patients established ≥ 3 months on IV infliximab, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease [CD], or perianal CD [p = 0.55 and p = 0.11 at 9-12 months, and p = 0.50 at 6 months, respectively]. Neither prior IV dose [≤ 10 mg/kg 6-weekly] [p = 0.48] nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p = 0.48 and p = 0.45 [UC vs CD], respectively)., Conclusion: Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and a low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10 mg/kg 6-weekly. These data should provide patients and clinicians alike with confidence in SC infliximab use in IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Biologic medications are a common therapy for those with inflammatory bowel disease (IBD). There are limited data on the outcomes of home-based biologic infusions for patients with IBD. The aim of this study was to compare the safety and efficacy of biologic infusions for IBD patients who receive either home- or office-based administration., Methods: Patients receiving infliximab or vedolizumab were analyzed retrospectively over a period of 152 weeks. Survival free of major adverse events including delayed infusion reaction, steroid initiation, drug discontinuation, or IBD-related emergency department visits, admission, and surgery were compared using a Kaplan-Meier curve. Individual adverse events, infusion-.related quality measures, and markers of patient adherence were analyzed., Results: Adverse event-free survival was greater among those receiving home-based infusion (n = 154) compared with office-based infusion (n = 133). The office infusion cohort had higher rates of delayed infusion reactions (4 vs 0), IBD-related surgery (6 vs 0), and drug discontinuation (44 vs 35); this was a sicker cohort of patients compared with those in the home infusion group. Home infusion patients were less likely to receive correct weight-based dosing for infliximab (71.7% vs 89.3%), obtain labs for drug monitoring (53.2% vs 71.4%), and adhere to routine clinic visits (37.9% vs 58.1%)., Conclusions: The home-based infusion of biologics for IBD appears safe with lower rates of major adverse events compared with office-based infusions. However, those receiving home infusion were less likely to receive correct weight-based dosing for infliximab and were poorly adherent to routine follow-up., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The optimal infliximab dose intensification strategy to address loss of response associated with subtherapeutic infliximab trough levels remains uncertain, as does whether post-intensification trough and treatment targets should influence this decision., Objectives: This pharmacokinetic simulation study aimed to identify infliximab dose intensification strategies capable of achieving post-intensification infliximab trough thresholds associated with clinical and objective treatment targets in Crohn's disease and ulcerative colitis., Methods: A validated pharmacokinetic infliximab model, applied to 200 simulated patients, identified those with subtherapeutic (< 3.00 mg/L) trough levels after 30 weeks of standard (5 mg/kg 8-weekly) dosing, and subsequently applied 10 dose intensification strategies over a further 32 weeks. The proportion of simulations achieving 32-week post-intensification infliximab trough levels associated with endoscopic remission (ulcerative colitis > 7.50 mg/L, Crohn's disease > 9.70 mg/L) was the primary outcome, with perianal fistula healing (Crohn's disease > 10.10 mg/L) and clinical improvement (ulcerative colitis > 3.70 mg/L, Crohn's disease > 7.00mg/L) evaluated as secondary outcomes. All outcomes were stratified by intensity of dose intensification, with standard (≤ 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) and intensive (> 10 mg/kg 8-weekly or 5 mg/kg 4-weekly; n = 5) dosing strategies defined, respectively., Results: The median pre-intensification infliximab trough level was 0.91 mg/L (interquartile range 1.37). Intensive dosing strategies were more likely to achieve infliximab trough concentrations associated with endoscopic remission (ulcerative colitis 36.48% vs. 10.80%, Crohn's disease 25.98 vs. 4.68%), perianal fistula healing (24.52% vs. 4.36%) and clinical improvement (ulcerative colitis 61.90% vs. 34.86%, Crohn's disease 40.32 vs. 12.08%) than standard intensification strategies (all p < 0.01). When controlling for cumulative (mg/kg) infliximab dose over 32 weeks, strategies that concurrently dose increased and interval shortened achieved the highest infliximab trough levels (all p < 0.01)., Conclusion: This simulation-based analysis highlights the potential of using post-intensification infliximab trough thresholds associated with aspirational treatment targets in Crohn's disease and ulcerative colitis to guide choice of infliximab dose intensification strategy. Intensive dose intensification strategies, particularly those that concurrently dose increase and interval shorten, appear to achieve higher infliximab levels than standard dose intensification strategies. This may be particularly important in the pursuit of stringent endpoints, such as endoscopic remission and fistula healing, which have been consistently associated with higher infliximab trough levels. These findings require validation across real-world cohorts., (© 2024. The Author(s).)

Objectives: Multiple studies in patients with Crohn's disease (CD) treated with anti-tumor necrosis factor alpha agents have shown that proactive therapeutic drug monitoring (TDM) during the maintenance phase leads to improved outcomes. We aimed to assess whether accelerated (IFX) administration during induction resulted in improved outcomes., Methods: This retrospective study included CD patients aged 5-17.9 years that were treated with IFX. We compared outcomes of patients treated during induction with 5-8 mg/kg dosing at Weeks 0, 2, 6, and 14 (Group 1), versus accelerated dosing (≥8 mg/kg and/or >4 infusions until Week 14, Group 2) of IFX. Primary outcome was steroid-free clinical remission by Week 52., Results: Sixty-eight patients were included, of whom seven discontinued IFX before Week 14, due to infusion reactions, immunogenic failure, or primary nonresponse. Comparison of Group 1 (n = 25) and Group 2 (n = 36) showed similar clinical characteristics, as well as inflammatory markers, at IFX initiation. Despite receiving significantly more IFX, and reaching a higher trough level by Week 14 (10.3 ± 1.2 vs. 3.3 ± 0.7, p < 0.001), the median Pediatric Crohn's disease Activity Index (PCDAI) was slightly higher in Group 2 versus Group 1 (14 [5-20] vs. 5 [0-15], p = 0.02). However, at Weeks 26 and 52 the PCDAI and inflammatory markers were comparable between the groups. Moreover, about 70% in both groups achieved the desirable trough IFX levels by Week 52., Conclusion: Accelerated IFX dosing during induction did not result in improved outcomes up to 12 months follow-up. Prospective studies are required to determine the exact timing in which proactive TDM should be applied., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential. The aims of this study are: (i) to validate the predictive performance of existing IFX PopPK models using a cohort of children with IBD; and (ii) to perform a Bayesian estimation of the most suitable model to predict the next IFX concentrations., Methods: PubMed was searched for IFX PopPK models in children. Selected models were rebuilt and analysed using R. Model performance was assessed through goodness-of-fit-plots, residuals against time, prediction error and prediction-corrected visual predictive checks. The validation cohort consisted of 73 children with IBD who were treated with IFX in our centre between 2017 and 2023 (340 IFX measurements)., Results: We identified 9 PopPK models. Model bias for individual predicted values ranged from -9.29% to 8.01% compared to bias for population predicted values. The model by Vande Casteele et al. demonstrated superior performance (individual predicted bias 2.13, population predicted bias -6.11); upon Bayesian estimation, it predicted induction trough levels with median error of 12.95% but had a median error of -69% predicting maintenance concentrations., Conclusion: The model by Vande Casteele et al. displayed superior performance in initial evaluations but had a high error in estimating next IFX levels and can only be used in practice to predict induction levels., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues. However, it is currently not known how consistent predictions of mAb disposition are across PBPK modelling platforms. In this work PBPK simulations of IgG, adalimumab and infliximab were compared between three platforms (Simcyp, PK-Sim, and GastroPlus). Accuracy of predicted serum and tissue concentrations was assessed using observed data collected from the literature. Physiological and mAb related input parameters were also compared and sensitivity analyses were carried out to evaluate model behavior when input values were altered. Differences in serum kinetics of IgG between platforms were minimal for a dose of 1 mg/kg, but became more noticeable at higher dosages (> 100 mg/kg) and when reference (healthy) physiological input values were altered. Predicted serum concentrations of both adalimumab and infliximab were comparable across platforms, but were noticeably higher than observed values. Tissue concentrations differed remarkably between the platforms, both for total- and interstitial fluid (ISF) concentrations. The accuracy of total tissue concentrations was within a three-fold of observed values for all tissues, except for brain tissue concentrations, which were overpredicted. Predictions of tissue ISF concentrations were less accurate and were best captured by GastroPlus. Overall, these simulations show that the different PBPK platforms generally predict similar mAb serum concentrations, but variable tissue concentrations. Caution is therefore warranted when PBPK models are used to simulate effect site tissue concentrations of mAbs without data to verify the predictions., Competing Interests: Declarations. Conflict of interest: The authors report no conflict of interest., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Data on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited., Aims: To evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent., Methods: In this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14., Results: Overall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5-8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06-7.54], p = 0.037) and W52(OR=2.68[1.16-6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14-0.98], p = 0.046). After a median follow-up of 20.9 months[11.7-33.7]), 50.0%(52/104) patients had discontinued infliximab., Conclusion: Infliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant., (Copyright © 2024. Published by Elsevier Ltd.)

We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. (Funded by the National Institute for Health and Care Research and others.)., (Copyright © 2024 Massachusetts Medical Society.)

In recent years, increasing numbers of reports have described new onset or active disease flare of IgA nephropathy (IgAN) during administration of TNF-α inhibitor (TNFi) therapy for chronic inflammatory diseases. Crohn's disease (CD) is the most common indication for TNFi therapy in this clinical setting, but the underlying etiology of IgAN in such patients remains unclear. We report our experience with three patients who developed acute worsening of preexisting urinalysis abnormalities and kidney dysfunction approximately 2 to 6 years after TNFi administration for CD. Kidney biopsies at the time of kidney disease flare revealed IgAN in two patients and IgAN complicated by acute tubulointerstitial nephritis in one patient. The CD and IgAN in all three patients were successfully managed with additional corticosteroid therapy and tonsillectomy without discontinuing TNFi therapy. The clinical course of our patients and similar patients described in the literature suggests that TNFi therapy for CD is associated with a relatively high risk for new onset or disease flare of IgAN. This report discusses the possible involvement of Th1/Th2 imbalance on the immunological background of CD or IgAN., (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Introduction: Expeditious initiation of biologic therapy is important in patients with inflammatory bowel disease (IBD). However, initiation of biologics in the outpatient setting may be delayed by various clinical, social, and financial variables., Aim: To evaluate the delay in initiation of an advanced therapy in IBD and to identify factors that contributed to this delay., Methods: This was a multi-center retrospective study. Outpatients who were initiated on a biologic therapy from 3/1/2019 to 9/30/20 were eligible for the study. Univariate and multivariate linear regression analyses were performed to identify variables associated with a delay in biologic treatment initiation. Delay was defined as the days from decision date (prescription placement) to first infusion or delivery of medication., Results: In total 411 patients (Crohn's disease, n = 276; ulcerative colitis, n = 129) were included in the analysis. The median [interquartile range-(IQR)] delay for all drugs was 20 [12-37] days (infliximab, 19 [13-33] days; adalimumab, 10 [5-26] days; vedolizumab, 21 [14-42] days; and ustekinumab, 21 [14-42] days). Multivariate linear regression analysis identified that the most important variables associated with delays in biologic treatment initiation was self-identification as Black, longer distance from treatment site, and lack of initial insurance coverage approval., Conclusion: There may be a significant delay in biologic treatment initiation in patients with IBD. The most important variables associated with this delay included self-identification as Black, longer distance from site, and lack of initial insurance coverage approval., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tumor necrosis factor-α inhibitors (TNFis) are used for the treatment of inflammatory bowel disease (IBD). The aim of this study was to evaluate the association between neurological adverse events (AEs) and TNFi use., Methods: Data of TNFis indicated for IBD were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the marketed date to the second quarter of 2023. The reporting odds ratio (ROR) and a Bayesian confidence propagation neural network were used to identify signals., Results: A total of 4,964 neurological AEs were reported in the IBD population. Infliximab had 3 signals, including demyelination [ROR (95% CI): 1.69 (1.33,2.15)], meningitis listeria [ROR (95% CI): 5.05 (3.52,7.25)], and optic neuritis [ROR (95% CI): 1.72 (1.3,2.26)]. The signals for adalimumab were gait disturbance [ROR (95% CI): 1.43 (1.32,1.56)] and muscular weakness [ROR (95% CI): 1.4 (1.27,1.55)]. A peripheral neuropathy signal was found for adalimumab [ROR (95% CI): 1.34 (1.18,1.53)] and certolizumab pegol [ROR (95% CI): 1.49 (1.07,2.08)]. However, there were no signals among neurological AEs for golimumab., Conclusion: Neurological signals were detected for TNFi use, indicating that the risk of neurological AEs requires additional attention in clinical use of TNFis.

Introduction: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring., Methods and Analysis: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants., Ethics and Dissemination: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment., Trial Registration Number: ACTRN12622001458729., Competing Interests: Competing interests: RDL has received conference fees from Janssen and Celltrion Healthcare. AS has received speaker fees from Sandoz and received research support and advisory fees from AbbVie, Pfizer, and Arrow Pharmaceuticals. GJW has served as a speaker, a consultant or an advisory board member for Janssen, Galapagos, AbbVie, Ferring, Dr Falk Pharma, Nova Labs and Sandoz. GTM has received educational grants or research support from GESA, The Gutsy Group, NHMRC, MRFF, AbbVie, Janssen, Pfizer, Shire and Takeda; speaker fees from AbbVie, Ferring, Janssen, Orphan, Pfizer, Roche, Sandoz, Shire and Takeda and has serve on advisory boards for AbbVie, Emerge, Eli-Lilly, Gilead, Hospira, Janssen, Orphan, MSD, Pfizer, Shire and Takeda. KL declares speaker fees, advisory Board fees and/or conference travel/registration support from AbbVie, Bristol Myers Squibb, Chiesi, Dr Falk, Ferring, Gilead, Guidepoint, Intercept Pharmaceuticals, Janssen-Cilag, MSD, Norgine, Pfizer, Sandoz, Takeda and the RAH Research Fund. JA has served as a speaker, a consultant and an advisory board member for, and has received research funding from, Abbott, AbbVie, Allergan, Anatara, AstraZeneca, Bayer, Celgene, Falk, Ferring, Gilead, Hospira, Immunic, ImmunsanT, Janssen, MSD, Nestle, Progenity, Pfizer, Sandoz, Shire, Takeda, Vifor, RAH Research Fund, The Hospital Research Fund with all monies received by her department for research support. YKA reports grants from Janssen, during the conduct of the study; has received speaking and consulting fees from AbbVie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards for AbbVie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Microba and received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. RVB has received grant/research support/speaker fees from AbbVie, Ferring, Janssen, Shire, Takeda, Bristol Myer Squibb and Emerge Health; and is a shareholder in Biomebank. SC declares advisory board participation, speaker fees, educational support and/or research support for Liverpool Hospital, South Western Sydney Local Health District (SWSLHD) Academic Unit or Crohn’s Colitis Cure from: AbbVie, Amgen, BMS, Celltrion, Chiesi, Eli-Lilly, Dr Falk, Ferring, Fresenius Kabi, Gilead, GSK, Janssen, MSD, Novartis, Organon, Pfizer, Sandoz, Takeda and non-pharmacological research support from Agency for Clinical Innovation, Gastroenterological Society of Australia, The Leona M and Harry B Helmsley Charitable Trust, Medical Research Future Fund, SWSLHD, Sydney Partnership for Health, Research and Enterprise (SPHERE). MG has served on the advisory board of Pfizer and has received speaker fees, research or travel grants from AbbVie, Celltrion, Dr Falk, Janssen, Pfizer, Pharmacosmos, Takeda. EKW declares speaker and consulting fees from AbbVie, BMS, Celltrion, Falk, Ferring, Janssen, Pfizer and research funding/support from AbbVie, Ferring, Janssen. JPS has received conference fees from Janssen, BMS, Takeda, educational grants from Pfizer, speaker fees from AbbVie, Takeda and Pfizer and an unrestricted grant from Tillots. PDC has served as a consultant, an advisory board member or a speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion, Emerge Health, Shire and Takeda and received research support from Ferring, Shire, Janssen, AbbVie, and Takeda. MGW has received educational grants and speakers fees from AbbVie, Takeda and Ferring; travel grants from Pfizer; and has served on advisory boards for AbbVie. MPS has received educational grants or research support from Ferring, Orphan and Gilead; speakers fees from Janssen, AbbVie, Ferring, Takeda, Pfizer and Shire; and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead and BMS. JM, PH, RBG, DC, MS, EC, LT, GH and AB declare no relevant competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities., Methods: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups., Results: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 μg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 μg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 μg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 μg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 μg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083)., Conclusion: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose., (© 2024. Springer Nature Switzerland AG.)

Background/aims: Studies on elective switching to the subcutaneous (SC) formulation of infliximab revealed comparable efficacy and safety and higher infliximab level than those exhibited by intravenous (IV) infliximab. However, no studies have reported on the effectiveness of SC switching in ulcerative colitis (UC) patients who experienced IV infliximab failure during maintenance treatment., Methods: This retrospective study included UC patients who had been switched to SC infliximab because of IV infliximab failure, between January 2021 and January 2023. Group A was defined as having clinically and biochemically active UC (secondary loss of response), and group B consisted of patients with stable symptoms but biochemically active UC., Results: Twenty-three patients met the inclusion criteria: 15 in group A and eight in group B. The serum infliximab levels significantly increased after SC switching in both groups. The electively switched group also exhibited increased infliximab levels after SC switching. Patients in group A showed improved partial Mayo score with a significant decrease in fecal calprotectin and C-reactive protein after switching. In group B, the fecal calprotectin level significantly decreased without clinical relapse after switching. A high proportion of patients (≥80%) in both groups achieved clinical and/or biochemical responses at the last follow-up. During the follow-up period, only two patients in group A discontinued SC infliximab, and only one complained of severe injection site reaction., Conclusions: In UC patients who experience IV infliximab failure during maintenance treatment, switching to SC infliximab may be a promising option because of better efficacy and safety.

A 15-year-old girl had experienced hip pain at 11 years of age. At 15 years of age, the patient complained of persistent generalised pain. Her rheumatoid factor and serum matrix metalloproteinase-3 levels were below standard values; there were no inflammatory responses, and the human leukocyte antigen test was negative for B27 and positive for B52 and B62. The bath ankylosing spondylitis disease activity index (BASDAI) value was 8.0 at the time of induction and 3.1 at 6 months after the introduction of adalimumab (at a dose of 40 mg). The BASDAI value improved with an increase in the dose of adalimumab to 80 mg at 8 months after the initial introduction of adalimumab (at 40 mg), although it remained at 4.8 at 16 months after the dose increase. The BASDAI value was 2.6 at 6 months, 2.7 at 1 year, and 1.8 at 1.5 years after the introduction of infliximab, indicating that the patient had progressed well without any adverse events. Based on this case, juvenile ankylosing spondylitis is a differential diagnosis for low back pain and generalised pain since childhood. Tumour necrosis factor (TNF) inhibitors were promptly introduced in this case, although it took 4 years from the initial presentation. TNF inhibitors were effective in treating juvenile ankylosing spondylitis in the present case without any adverse events. This case is notable because juvenile onset ankylosing spondylitis is one of the reasons for severe lumbago since childhood and because TNF inhibitors were administered promptly after diagnosis., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objective: Infliximab is indicated for a wide range of diseases, and infusion reactions (IRs) have been reported after infliximab administration in 17.6% of patients in clinical practice. This study aimed to identify the risk factors for IRs before the administration of infliximab based on available patient information., Materials and Methods: We retrospectively analyzed patients treated with infliximab. Data were compared between patients with and without IRs immediately before initiation of infliximab., Results: Elevated C-reactive protein (CRP) (odds ratio (OR), 2.150; 95% confidence interval (CI), 1.329 - 3.477; p = 0.002) before infliximab administration was a significant risk factor for developing an IR., Conclusion: Patients with elevated CRP levels before therapy initiation may require more careful monitoring after infliximab administration.

Objectives: The severe course of inflammatory bowel diseases (IBDs) refractory to advanced therapies in children results in the search for new therapeutic methods. The aim of this study was to evaluate the efficacy and safety of dual therapy with biologics in a cohort of children with IBD., Methods: Retrospective analysis of data from 29 children with a diagnosis of IBD, 19 with ulcerative colitis (66%), 10 with Crohn's disease (CD) (34%) qualified for dual biological therapy (DBT). The median age of patients was five (interquartile range [IQR], 1-15) years at diagnosis of IBD and 14 (IQR, 3-17) years at eligibility for dual therapy. Thirteen (45%) patients were treated with vedolizumab/adalimumab (VDZ + ADA), 13 (45%) with ustekinumab/adalimumab (UST + ADA), three (10%) with infliximab/vedolizumab (IFX + VDZ)., Results: Clinical remission was achieved in 13 (45%; seven UC and six CD) and 12 (41%; seven UC and five CD) Pediatric Weighted Crohn's Disease Activity Index (wPCDAI)/Pediatric Ulcerative Colitis Activity Index (PUCAI) patients after 4 and 12 months at the initiation of dual therapy. Clinical response based on wPCDAI/PUCAI was reported in 16 (55%; nine UC and seven CD) and 12 (41% seven UC and five CD) children after 4 and 12 months of follow-up, respectively. The median fecal calprotectin decreased significantly from 1240 µg/g (53-10,100) to 160 µg/g (5-2500; p = 0.004) between baseline and Month 4 and from 749 at baseline (57-10,100) to 17 (5-3110; p = 0.12) over 12 months. Moreover, 34% (six UC and four CD) of patients achieved endoscopic remission., Conclusions: DBT seems to be an effective alternative therapeutic option for patients with moderate and severe IBD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers., Methods: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication., Results: Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX., Conclusions: Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches., Protocol Registration: www.crd.york.ac.uk/prospero identifier is CRD42021289144.

Objectives: Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients., Methods: In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD., Results: During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response., Conclusion: Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose of Review: This review details the three new agents, including two novel mechanisms of action, approved to treat Crohn's disease in recent years. We review efficacy, safety, prescribing information, and available data on positioning these new therapies., Recent Findings: Risankizumab and upadacitinib are novel mechanisms of action approved to treat moderate to severe Crohn's disease. Risankizumab targets the cytokine interleukin-23. Upadacitinib is a selective Janus kinase-1 inhibitor approved for use in individuals who have previously failed or are intolerant to an anti-TNF agent. Subcutaneous infliximab provides a novel method of administering maintenance dosing of a longstanding and efficacious therapy., Summary: Risankizumab has shown efficacy in both biologic naïve and biologic experienced populations. The SEQUENCE trial shows superiority of risankizumab over ustekinumab for disease response in patients who have previously failed an anti-tumor necrosis factor agent. Upadacitinib has shown good efficacy in clinical trials even in the setting of a mandated steroid taper during induction. Subcutaneous infliximab maintenance therapy appears noninferior to i.v. infliximab and shows good treatment persistence in real world transitions. Additional data is needed to better understand how to position these therapies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies., Methods: Patients with Crohn's disease or ulcerative colitis received CT‑P13 IV loading doses (5 mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CT‑P13 IV (5 mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed., Results: Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3 µg/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch., Conclusion: Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Biologic drugs are highly effective for inflammatory bowel disease (IBD) management but are key drivers of costs of care especially when administered intravenously (i.v.). Availability of subcutaneous (SC) formulations has increased convenience for patients and improved access to care, but at the cost of revenue to health services., Aims: To evaluate the economic impact of transitioning a tertiary centre IBD cohort from i.v. to SC biologic administration and assess the implications for key stakeholders., Methods: A retrospective analysis of all patients who received i.v. infliximab or vedolizumab in the outpatient infusion centre of a tertiary IBD centre between July 2019 and June 2021 was undertaken. Data were collated from electronic medical records, pharmacy dispensing systems and the hospital business intelligence unit. An economic analysis and theoretical financial/capacity impact analysis of a transition to an SC model were estimated under two scenarios using a random 10% and 30% of the patient cohort., Results: Transitioning our IBD cohort from i.v. to SC administration would result in a loss to our health service of AU$2 732 123.75, composed of AU$1 463 003.75 in Weighted Inlier Equivalent Separation (WIES) and AU$1 269 120 in drug procurement revenue. However, it would ease capacity in the infusion centre by up to 5256 h., Conclusions: Transitioning patients to SC administration results in improved access to infusion centres and substantial savings to state governments; however, switching results in a loss of i.v. biologic-generated WIES to health services. Alternative funding models are required to achieve sustainability in IBD care and reduce reliance on i.v. biologic-generated income., (© 2024 Royal Australasian College of Physicians.)