Anti-infliximab antibody concentrations can guide treatment intensification in patients with Crohn's disease who lose clinical response.

BACKGROUND: The presence of antibodies towards infliximab (ATI) is associated with lower infliximab (IFX) trough concentrations and loss of response. IFX treatment intensification is effective for restoring response in most, but not all patients with Crohn's disease (CD). AIM: To compare outcome, pharmacokinetics and immunogenicity of treatment intensification strategies in patients with CD who lost clinical response to IFX. METHODS: A retrospective cohort study was conducted, including 103 patients with CD who lost clinical response during IFX maintenance therapy and therefore received a double dose IFX (10 mg/kg) and/or a next infusion after a shortened interval. IFX and ATI concentrations were measured in consecutive trough samples, just before (T0) and after (T+1) treatment intensification. RESULTS: Clinical response (physicians' global assessment) and biological response and remission (CRP) were restored in 63%, 42% and 24% of patients (evaluated at T+1). Treatment intensification increased IFX trough concentrations from 1.2 µg/mL [0.3-3.6] at T0 to 3.6 µg/mL [0.5-10.2] at T+1 (P < .0001). Using a drug tolerant assay, ATI were detected in the T0 sample of 47% of patients. ATI negatively impacted the achieved IFX trough concentration (Spearman r -0.57, P < .0001) and the probability of clinical response (P = 0.034) at T+1. When ATI were quantifiable but <282 ng/mL eq. at T0, combined interval shortening and dose doubling was more effective for restoring therapeutic IFX trough concentrations (≥3 µg/mL at T+1) than dose doubling alone, which in turn was more effective than interval shortening alone (P < .001). CONCLUSION: Antibodies towards infliximab can guide clinical decision-making on treatment intensification.

Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases.

BACKGROUND: Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD. AIM: To review the literature on anti-TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. METHODS: A PubMed literature search was performed using the following terms individually or in combination: 'biosimilars,' 'CT-P13,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'anti-TNFα therapy,' 'infliximab,' 'adalimumab,' 'pharmacokinetics,' 'immunogenicity.' RESULTS: Bioequivalence of CT-P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short-term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti-drug antibodies and whether similar exposure-response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. CONCLUSIONS: It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years.