Infliximab In Colitis Research Articles

Infliximab in Inflammatory Bowel Disease: Leveraging Physiologically Based Pharmacokinetic Modeling in the Clinical Context.

In this study, a physiologically based pharmacokinetic (PBPK) modeling framework was employed to explore infliximab exposure following intravenous (5 mg/kg) and subcutaneous administration (encompassing the approved 120 mg flat-fixed dose as a switching option) in virtual adult and pediatric patients with inflammatory bowel disease (IBD). The PBPK model and corresponding simulations were conducted using the PK-Sim® software platform. The PBPK simulation indicated that a 120 mg subcutaneous flat-fixed dose might not be optimal for heavier adults with IBD, suggesting the need for infliximab dose escalation. For an older virtual pediatric patient (14 years old), subcutaneous administration of a 120 mg flat-fixed dose appears to be a feasible IBD treatment option. In the final exploration scenario, the model was extended to predict hypothetical subcutaneous infliximab doses in a virtual pediatric population (6-18 years old), stratified into three weight bands (20-30 kg, 30-45 kg, and 45-70 kg), that would yield post-switch trough concentrations of infliximab comparable to those seen in adults with the 120 mg flat-fixed subcutaneous dose. The PBPK-model-informed dose suggestions were 40 mg for the 20-30 kg band, 80 mg for the 30-45 kg band, and 120 mg for the 45-70 kg band. As demonstrated in this paper, the PBPK modeling framework can serve as a versatile tool in clinical pharmacology to investigate various clinical scenarios, such as exploring alternative dosing regimens and routes of administration, ultimately advancing IBD treatment across diverse (sub)populations of clinical interest.

Evaluating the Efficacy of Infliximab in Inflammatory Bowel Disease: A Systematic Review of the Literature.

The introduction of steroid therapy in 1955 markedly decreased the mortality rate of severe ulcerative colitis (UC) from 24% in the placebo group to 7%, and it is currently less than 1% in specialist centers. Despite this advancement, the response of severe UC to steroids has stagnated over the past 50 years, with a high rate of colectomy persisting for severe to moderately severe cases. Infliximab (IFX) (Remicade, CentocorInc., Malvern, PA, United States), an intravenously administered chimeric monoclonal immunoglobulin G1 antibody targeting tumor necrosis factor-alpha (TNF-α), has shown efficacy in numerous randomized controlled trials for treating moderate to severe and fistulizing Crohn's disease, particularly in patients unresponsive to conventional therapies. This led to its approval by the US Food and Drug Administration in 1998 for treating active and fistulizing Crohn's disease. Most clinical research on IFX has focused on Crohn's disease, which is characterized as a Th1-type condition driven by pro-inflammatory cytokines like TNF-α. Conversely, UC has traditionally been viewed as a Th2-type condition where TNF-α plays a lesser role. However, recent studies indicate that TNF-α might also contribute to the pathogenesis of UC. These findings highlight the necessity for larger randomized controlled trials to further investigate the benefits of therapies like IFX, with the ultimate goal of improving treatment outcomes and quality of life for patients with inflammatory bowel disease.

Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial

IntroductionA 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....

P786 Evaluation of the efficacy and safety of the use of subcutaneous infliximab in the treatment of inflammatory bowel disease in naïve patients

Abstract Background The use of intravenous (IV) infliximab in inflammatory bowel disease (IBD) is an established treatment with a demonstrated safety and efficacy profile. Subcutaneous (SC) infliximab is currently available, showing comparable results in disease maintenance, but lacking studies in naïve patients. This study aims to determine whether initial treatment with SC infliximab is as effective and safe in real clinical practice. Methods This is a single-center observational study that included patients with clinically active IBD who directly initiated SC infliximab after IV induction (IV 5 mg/kg 0-2 weeks and SC 120 mg/2 weeks at week 6). The primary objective of the study was to evaluate the response to SC treatment at 3 and 9 months in patients naïve for infliximab. Secondary objectives included the need for intensification, rescue treatments (corticosteroids, change of biologic or surgery), the occurrence of adverse effects and pharmacokinetic aspects (blood levels, development of antibodies to infliximab or ATIs). Clinical activity was assessed using the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD) and Partial Mayo Score (PMS) for ulcerative colitis (UC). In addition, biochemical parameters (hemoglobin, albumin, C-reactive protein, and fecal calprotectin) were monitored. Results A total of 19 patients were included, 14 with CD and 5 with UC (Table 1). Among them, 16/19 had not received previous biological treatment and 3/19 had received another anti-TNF other than infliximab. They were followed at 3 (18/19) and 9 months (18/19) (Figure 1). Significant improvement (p<0.05) was observed in the parameters of clinical activity (6/18 persisting with mild-moderate activity at 9 months) and biochemical activity (fecal calprotectin). Infliximab levels were adequate at 3 (median 12; range 3.2-39) and 9 months (median 15.9; range 0.3-51). In total, 31.6% of patients (6/19) discontinued treatment: 1/19 due to mild acute urticaria at baseline, 2/19 due to the development of ATIs (one also developed lung abscesses requiring hospitalization) and 3/19 due to loss of secondary response requiring a change of biologic. Of the latter, one also needed treatment with oral corticosteroids. In none of the patients was the treatment intensified or surgery required. Conclusion Treatment with SC infliximab in naïve patients seems to be an effective and safe alternative with results comparable to IV infliximab in real clinical practice. In our 9-month study, clinical scores and fecal calprotectin improved significantly, with low immunogenicity rates. Only 31.6% of patients discontinued treatment due to adverse effects or loss of response. Table 1. Baseline characteristics of patients

P960 Comparison of clinical outcomes by induction therapy response status in patients with Inflammatory Bowel Disease (IBD) treated with subcutaneous (SC) versus intravenous (IV) infliximab (IFX): Post hoc analysis of a pivotal, randomised controlled trial

Abstract Background Clinical associations between initial response and long-term outcome are well established for IV IFX in IBD.1,2 In 2020, SC IFX was approved in Europe for treating moderate-to-severe Crohn’s disease (CD) or ulcerative colitis (UC), based on a pivotal randomised trial (NCT02883452) comparing SC and IV IFX.3 This post hoc analysis investigated clinical outcomes in patients (pts) treated with SC or IV IFX, by response to IV IFX induction. Methods In the pivotal trial, adults with active CD or UC received IV IFX induction (5 mg/kg; Week [W] 0 and W2), before randomisation to SC (n=66) or IV (n=65) arms. W6 clinical response (≥70-point decrease in Crohn’s Disease Activity Index [CDAI] score [CD]; ≥2-point decrease in partial Mayo score with ≥1-point decrease in rectal bleeding subscore or an absolute rectal bleeding subscore of 0 or 1 [UC]) was a stratification factor. The SC arm received SC IFX (120/240 mg for pts weighing <80/≥80 kg) every 2 weeks from W6–54; the IV arm received IV IFX 5 mg/kg every 8 weeks (W6–22), then switched to SC IFX (W30–54). Rates of clinical remission (CDAI score <150 [CD]; partial Mayo score ≤1 [UC]) and trough IFX concentrations (Ctrough) were assessed at W6, W30 and W54. Analyses were descriptive. Results There were 101 induction responders (IRs) to IV IFX, who were randomised to the SC arm (n=49, 74.2%; SC-IR subset) or the IV arm (n=52, 80.0%; IV-IR subset). Correspondingly, there were 17 (25.8%) and 13 (20.0%) induction non-responders (INRs; SC-INR and IV-INR subsets, respectively). In both study arms, IRs had higher clinical remission rates than INRs at both W30 and W54 (Figure A). Comparing by formulation, the SC-INR subset had nearly twice the W30 clinical remission rate of the IV-INR subset (58.8% vs. 30.8%; p=0.159 [Fisher exact test]). In addition, IV-INR subset clinical remission rates numerically increased after pts switched to SC IFX (W30: 30.8% vs. W54: 46.2%; p=0.476 [McNemar test]). These observations were generally consistent with Ctrough findings (Figure B); median Ctrough in the IV-INR subset increased from 1.5 to 18.3 µg/mL (p=0.005 [Wilcoxon signe-drank test]) after switching to SC IFX. Conclusion Findings suggested associations between initial response to IFX induction therapy and positive long-term outcomes for both SC and IV IFX, and supported potential benefits with SC IFX maintenance therapy for INRs, compared with the option of IV IFX maintenance. Given the post hoc nature of the analysis and the small analysis population (thus statistical inconclusiveness), investigation in larger studies is warranted. 1Murthy SK et al. Inflamm Bowel Dis 2015;21:2090–6. 2Wong ECL et al. J Crohns Colitis 2021;15:1114–9. 3Schreiber S et al. Gastroenterology 2021;160:2340–53.

Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

S866 Secondary Non-Immune Loss of Response to Long Term Maintenance Therapy With Infliximab for Inflammatory Bowel Disease is Not Due to Inadequate Trough Levels

S866 Secondary Non-Immune Loss of Response to Long Term Maintenance Therapy With Infliximab for Inflammatory Bowel Disease is Not Due to Inadequate Trough Levels

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study

BackgroundStudies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. ObjectiveTo compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. MethodsA retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. ResultsA total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). ConclusionOur study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

Oral colon-targeted responsive alginate/hyaluronic acid-based hydrogel propels the application of infliximab in colitis

Currently, commercialized infliximab (IFX) has rapidly propelled the clinical treatment of IBD, however, its inherent attributes, such as off-target effects and rapid metabolism, severely limit practical applications. Moreover, high doses injection of IFX can result in IBD treatment failure, which may induce other side effects. In this study, an colon microenvironment-responsive hydrogel (AL/HA hydrogel), consisting of acid-resistant sodium alginate and colon-degraded and targeted hyaluronic acid, was constructed by simple Ca2+/Zn2+ cross-linking. The ion-mediated hydrogel exhibited the protective effect of gastrointestinal tract to avoid early drug leakage, while the inflammation environments showed well-controlled drug release and significant biodegradable behaviors. Additionally, oral hydrogel exhibited long-standing enteritis areas compared with normal mice. Therefore, hydrogel-assisted enteritis treatment has great potential in IBD as an oral agent. After that, IFX was packaged in hydrogel to fabricate a facile oral antibody delivery system to treat IBD. IFX-embedded hydrogel showed remarkable therapeutic effect on IBD compared with free IFX. Surprisingly, oral hydrogel below 7 times IFX achieve the same amount of IFX-infused treatment that will further help alleviate the drawbacks of IFX. Our work elaborated on the efficacy of oral AL/HA@IFX in IBD, providing a guarantee for the future of promoted clinical transformation.

Association between 6-thioguanine nucleotide levels and preventing production of antibodies to infliximab in patients with inflammatory bowel disease

ObjectiveCombination therapy with infliximab and a thiopurine has been shown to be more effective than monotherapy in patients with inflammatory bowel disease (IBD). The therapeutic efficacy of thiopurines is correlated...

Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.

DOP86 Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn’s disease: A phase 3, randomised, placebo-controlled study (LIBERTY-CD).

Abstract Background CT-P13 subcutaneous (SC) infliximab formulation showed comparable efficacy and safety with CT-P13 intravenous (IV) infliximab in inflammatory bowel disease (IBD)1 and rheumatoid arthritis2. This study aimed to demonstrate the superiority of CT-P13 SC over placebo as maintenance therapy after induction therapy of CT-P13 IV in patient with Crohn’s disease (CD). Methods Moderately to severely active CD patients with Crohn’s disease activity index (CDAI) score 220 to 450 and simplified endoscopic activity score for Crohn’s disease (SES-CD) of ≥6 points for ileal-colonic CD or ≥4 points including ulcer score from at least 1 segment for ileal CD or colonic CD were enrolled LIBERTY-CD study (NCT03945019) and treated with open-label CT-P13 IV 5 mg/kg at Weeks 0, 2 and 6 as induction therapy. At Week 10, patients who had a clinical response were randomised (2:1) to receive either CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks up to Week 54. At Week 54, clinical remission and endoscopic response were assessed as co-primary endpoints. Clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission were assessed at Week 54 as key secondary endpoint. Safety was evaluated up to Week 54. Results A total of 396 patients were enrolled and 343 patients (86.6%) were randomised (231 in CT-P13 SC arm and 112 in placebo arm) at Week 10. At Week 54, the clinical remission rate was greater in CT-P13 SC arm than placebo arm (62.3% and 32.1% respectively, with P &amp;lt;0.0001). The endoscopic response rate was also greater in CT-P13 arm than placebo arm (51.1% and 17.9% respectively, with P &amp;lt;0.0001). CT-P13 SC also had significantly greater efficacy on key secondary endpoints results compared to placebo arm (Table 1). Safety profiles were generally comparable between CT-P13 SC and placebo arms, but a single death was reported during the maintenance phase (Table 2). Conclusion CT-P13 SC was more effective than placebo in clinical remission, endoscopic response, clinical response, clinical remission (alternative definition), endoscopic remission, and corticosteroid-free remission at Week 54. No new safety concerns were found during treatment of CT-P13 SC. These results demonstrate that maintenance therapy with CT-P13 SC provides both a robust clinical benefit and the convenience of SC administration to moderately to severely active CD patients. [1] Schreiber et al., 2021. Gastroenterology 2021;160:2340–23 [2] Westhovens et al., 2020. Rheumatology 2020;00:1

Clinical, Laboratory, and Endoscopic Efficacy of Adalimumab and Infliximab in Inflammatory Bowel Disease

Clinical, Laboratory, and Endoscopic Efficacy of Adalimumab and Infliximab in Inflammatory Bowel Disease

Therapeutic Drug Monitoring of Subcutaneous Infliximab in Inflammatory Bowel Disease-Understanding Pharmacokinetics and Exposure Response Relationships in a New Era of Subcutaneous Biologics.

CT-P13 is the first subcutaneous infliximab molecule approved for the management of inflammatory bowel disease (IBD). Compared to intravenous therapy, SC infliximab offers a range of practical, micro- and macroeconomic advantages. Data from the rheumatological literature suggest that subcutaneous CT-P13 may lead to superior disease outcomes in comparison to intravenous infliximab. Existing studies in IBD have focussed on pharmacokinetic comparisons and are inadequately powered to evaluate efficacy and safety differences between the two modes of administration. However, emerging clinical trial and real-world data support comparable clinical, biochemical, endoscopic and safety outcomes between subcutaneous and intravenous infliximab in both luminal Crohn’s disease and ulcerative colitis. Across the available data, subcutaneous CT-P13 provides relative pharmacokinetic stability and higher trough drug levels when compared to intravenous administration. The clinical impact of this observation on immunogenicity and treatment persistence is yet to be determined. Trough levels between the two methods of administration should not be compared in isolation as any subcutaneous advantage must be considered in the context of comparable total drug exposure and the theoretical disadvantage of lower peak concentrations compared to intravenous therapy. Furthermore, target drug levels for subcutaneous CT-P13 associated with remission are not known. In this review, we present the available literature surrounding the pharmacokinetics of subcutaneous CT-P13 in the context of therapeutic drug monitoring and highlight the potential significance of these observations on the clinical management of patients with IBD.

The Nocebo Effect in a Non-Medical Switching Program from Originator to Biosimilar Infliximab in Inflammatory Bowel Disease.

Despite growing awareness of the nocebo effect, few studies have evaluated the nocebo effect using combined assessment of patient-reported outcome measures (PROMs), clinical indices, and objective biomarkers in inflammatory bowel disease (IBD) patients switching from originator to biosimilar medicines. This study aimed to compare these outcomes across switch and non-switch cohorts to evaluate the nocebo effect in patients with IBD. Parallel cohorts of IBD patients who (1) switched from originator to biosimilar (CT-P13) infliximab and (2) continued biosimilar (CT-P13) infliximab were evaluated over 32 weeks. Clinical disease activity, objective biomarkers and PROMs were assessed at baseline, and weeks 16 and 32 across both cohorts. The PROM of interest was patient-perceived disease activity evaluated using a 0-100 visual analogue scale (VAS) per the IBD-Control Questionnaire. Of 81 patients, 47 switched from originator to biosimilar (CT-P13) infliximab. A negative change from baseline patient-reported disease control was observed across the switch cohort compared with the non-switch cohort at week 16 (mean VAS - 8.21 vs. 1.26; p=0.03), but not at week 32 (mean VAS - 1.21 vs. 1.38; p=0.58). Corresponding clinical and objective biomarker assessments over these timepoints were comparable across both cohorts. This study demonstrated a temporary yet discernible nocebo effect in the first 16 weeks following non-medical switching that was not sustained at week 32. Negative patient perceptions may be overcome by a patient-inclusive approach to non-medical switching in conjunction with close clinical follow-up and disease monitoring.

Safety, satisfaction and cost savings of accelerated infusions of standard and intensified-dose infliximab for inflammatory bowel disease.

Infliximab remains a mainstay for the treatment of inflammatory bowel disease (IBD), but a long infusion duration and subsequent monitoring can be burdensome to patients and healthcare providers. To assess the safety of accelerated infusions for standard and dose-intensified infliximab regimens, and the effect on patient satisfaction and potential cost savings. Patients with IBD on a stable maintenance dose of infliximab and in clinical remission received one or more accelerated infusions: over 30 min if receiving a standard dose (5 mg/kg), or over 60 min if receiving dose-intensified infliximab (up to 10 mg/kg). Outcomes included incidence of reactions (acute or delayed), patient satisfaction and potential cost savings. We also explored infliximab trough levels after one and three accelerated infusions. Fifty-two patients who received 150 infusions were studied. Incidence of reactions to accelerated infusions was 3.3% (3 out of 89) with a standard dose and 0% (out of 61) with dose-intensified infliximab. Reactions were delayed, mild and self-limiting. None required drug cessation. Patient satisfaction was improved with shortened infusion time as compared with the patients' previous experiences (P = 0.00002). Mean plasma trough level of infliximab reduced from 9.3 mg/L (±4.9) to 7.9 mg/L (±4.1) (P = 0.02) with accelerated infusions, but none developed anti-infliximab antibodies. Nursing cost savings were estimated as $123.52 and $247.04 per patient per year for standard and dose-intensified infliximab respectively. Accelerated infliximab infusions for standard and dose-intensified regimens seem to be safe and improved patient satisfaction. Potential impact on drug trough levels requires further investigations.

P483 Patient-reported quality of life, anxiety, and depression associated with switching originator infliximab to biosimilar

Abstract Background Non-medical switching from biologics to biosimilars is becoming increasingly common. Previous studies have demonstrated efficacy and safety of switching originator to biosimilar infliximab in inflammatory bowel disease (IBD) patients. Limited data exist on patient-reported quality of life (QOL) and possible emotional duress associated with these switches. The purpose of this study was to describe the impact of non-medical switches to infliximab biosimilars on QOL, anxiety, and depression. Methods This was a retrospective review of all IBD patients switched from originator to infliximab biosimilar at a large multicenter gastroenterology private practise in Texas. Patients were asked to complete standardised questionnaires on a quarterly basis beginning 3/2021, concurrent with large US payor policy changes mandating non-medical biosimilar switches. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was used to assess disease-specific QOL. The Hospital Anxiety and Depression Scale (HADS) was used to determine anxiety and depression. All questionnaires through 10/2021 were collected and designated as “pre” or “post” based on the date of the patient’s non-medical switch to infliximab biosimilar. Wilcoxon rank sum test was used to compare scores. We also performed subset analyses on patients with both “pre” and “post” questionnaires with paired t-test. Results From 3/2021 to 10/2021, a total of 81 questionnaires were submitted by 54 patients who underwent non-medical switches to an infliximab biosimilar. 30 questionnaires were submitted prior to (“pre”) and 51 questionnaires were submitted after (“post”) the non-medical switch. Median “pre” SIBDQ score was 58 (IQR 53–63). Median “pre” HADS-Anxiety and HADS-Depression score were 3.5 (IQR 1–6) and 1 (IQR 0–5), respectively. As shown in Figure 1, “post” scores were unchanged [SIBDQ 59 (IQR 54–63); HADS-Anxiety 3 (IQR 1–7); HADS-Depression 2 (IQR 1–4)]. Subset analyses included 14 patients who submitted both “pre” and “post” questionnaires. Similarly, no significant changes were observed [Figure 2]. Conclusion Non-medical switches to infliximab biosimilar did not affect QOL or mental health. To our knowledge, this is the first biosimilar switch study to incorporate anxiety and depression measures. These relationships should continue to be assessed.

P479 Trends in medication use and treatment patterns in Chinese patients with Inflammatory Bowel Diseases: A multicenter cohort study from 1999 to 2020

Abstract Background The temporal changes in medication use and therapeutic paradigm in patients with Inflammatory bowel disease (IBD) have not been well elucidated in China over the past two decades. Therefore, we aimed to identify the temporal changes in medication use and treatment patterns for Chinese patients with IBD and to evaluate the factors associated with initial drug strategies. Methods A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) from January 1999 to December 2019. Medication utilization, treatment patterns, and associated factors with initial drug strategies were investigated. Results Prescriptions of 5-aminosalicylates (ASA) and corticosteroids (CS) gradually decreased, whereas prescriptions of immunosuppressants (IMS) and infliximab (IFX) increased in patients with CD. Except for stable prescriptions of ASA and CS, IMS and IFX increased since 2007 in patients with UC. Subgroup (N=957) analyses revealed that treatment patterns went through notable changes from ASA to IMS or IFX in patients with CD, while ASA and CS were still steadily prescribed in patients with UC. Logistic regression analyses revealed that perianal and gastrointestinal surgeries before diagnosis, disease behavior, and disease location were associated with different initial therapeutic strategies in patients with CD. However, medications before diagnosis, disease location, and diagnostic year might affect initial strategies in patients with UC. Conclusion Parallel to increasing uses of IMS and IFX in IBD over past two decades, a significant decrease in uses of ASA and CS were observed in CD, but not in UC. Treatment strategies analyses provided a unique insight in understanding long-term therapeutic patterns in the Chinese population.

Infliximab in inflammatory bowel disease. Is premedication necessary?

The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1–6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 h post infusion and late reactions for more than 24 h. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2–66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary. El uso de infliximab (IFX) en enfermedad inflamatoria intestinal (EII) se ha asociado con un riesgo de 1–6% de reacciones a la infusión. La utilidad de premedicación con corticoides, paracetamol y/o antihistamínicos es controvertido. Evaluar si en pacientes con EII que utilizan IFX hay diferencias en las reacciones secundarias a infusión entre aquellos que utilizan o no premedicación. Estudio descriptivo, observacional, retrospectivo en pacientes con EII, que han utilizado IFX entre enero 2009 y julio 2019. Se definieron como reacciones agudas aquellas ocurridas en las primeras 24 hrs.post infusión y tardías después de ese período, clasificándose en leves, moderadas y severas. Se usó estadística descriptiva y de asociación (χ 2; p < 0,05). Se incluyeron 1,263 infusiones en un total de 64 pacientes, 52% hombres. Mediana de infusiones por paciente 22 (2–66). El 100% de las infusiones en inducción fueron con premedicación y en mantenimiento el 57%. La premedicación fue realizada con hidrocortisona, clorfenamina y paracetamol. La mayoría de las reacciones fueron agudas, de gravedad leve a moderada y ningún paciente necesitó descontinuar IFX. En mantenimiento hubo 9/718 (1.2%) reacciones a la infusión con premedicación y 4/358 (1.1%) sin ésta, sin diferencias significativas (p = 0.606). En inducción hubo 8/187(4.3%) reacciones a la infusión, significativamente mayor al compararlas con ambos grupos de mantenimiento. En esta cohorte de pacientes, el no usar premedicación en fase de mantenimiento de IFX no aumentó el número de eventos adversos a este fármaco. Estos resultados sugieren que su indicación no sería necesaria.

Особенности ответа на инфликсимаб пациентов с воспалительными заболеваниями кишечника и анкилозирующим спондилитом

Aim: to compare the efficacy of infliximab in inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) and its relationship with drug concentration and the level of antibodies against this medication. Patients and Methods: this prospective observational study included 34 patients with AS, Crohn’s disease, and ulcerative colitis who received infliximab for 7.5 [5; 21.5] months. Treatment efficacy was assessed in all patients by a single measurement of trough concentration of infliximab and serum antibodies (Abs) against this medication. Results: infliximab was reported to be clinically effective in 63.6% of patients with IBD and 83.3% of patients with AS. Abs against infliximab were identified in 22.7% of patients with IBD and 25% of patients with AS. Low infliximab concentration was detected in 31% of patients Пациенwith IBD and 50% of patients with AS. Meanwhile, no significant differences between the groups were reported. Among patients with antiinfliximab Abs, a good treatment effect was observed in two patients (25%) who received therapy for &gt; 16 months. In patients with AS, infliximab inefficacy and infusion reactions were accounted for by the generation of Abs (66.7%) or low infliximab concentration (100%). Among patients with IBD, Abs and low infliximab concentration were identified only in 25% patients in whom infliximab was ineffective. In contrast to AS, certain factors affecting drug efficacy (i.e., hormone dependence and body mass index), its concentration (i.e., extraintestinal manifestation), and Ab levels (i.e., disease duration and body mass index) were identified in IBD. Conclusions: features identified that represent various mechanisms of immune escape and immunogenicity in inflammatory immunemediated disorders should be considered when extrapolating the data between disorders and developing management strategy for inadequate treatment response to infliximab. KEYWORDS: infliximab, ankylosing spondylitis, inflammatory bowel disease, trough concentration, antibodies against infliximab. FOR CITATION: Nuriakhmetova T.Yu., Valeeva I.Kh., Shevnina Ya.O. et al. Specificity of treatment response to infliximab in patients with inflammatory bowel disease and ankylosing spondylitis. Russian Medical Inquiry. 2021;5(2):64–70. DOI: 10.32364/2587-6821- 2021-5-2-64-70.