RESUMO
Background: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. Methods: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. Results: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 µg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (nâ =â 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (Pâ =â .0341), fecal calprotectin (Pâ =â .0002), and Harvey-Bradshaw index (P = .0029) since W0. Conclusions: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.
RESUMO
BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.
