ABSTRACT
Background: Recently, a subcutaneous formulation of biosimilar infliximab (CT-P13) (SC-IFX) has been approved for inflammatory bowel disease (IBD). The aims of this study were to evaluate efficacy, safety, pharmacokinetics and patient experience following a switching to SC-IFX in patients who are in clinical remission on IV-IFX maintenance treatment. Method(s): Multicentre, descriptive, and observational study including Crohn's disease (CD) and ulcerative colitis (UC) patients who were going to be changed from IV-IFX to SC-IFX on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD-GETECCU). All patients were on clinical and biological remission at least 24 weeks before changing. Demographic and disease data, clinical activity (Harvey-Bradshaw index for CD and mayo index for UC), analytical data (C reactive protein (CRP) and fecal calprotectin (FC), as well as trough levels were collected at baseline, at 12 and 24 weeks. Result(s): One hundred and fifty-five patients were included: 54 UC (35%) and 91 (65%) CD;44% women and 56% men;age 45.5 years (32-55). IV-IFX was mainly administered due to active disease (72%) and perianal disease (7%) and during 32 months [range 14-56]. Preswitch, 78 (50.3%) were on 8-weekly dosing of IV-IFX, 77 (49.7%) were with intensification dose and the half (50.3%) were on concomitant immunomodulatory therapy. SC-IFX was mainly switching by COVID-19 pandemic (60%), to increase through levels (15%) or patient request (25%). The majority of patients (140, 90%) remained with standard dose, 8 (5%) required dose intensification (120 mg weekly in 4 and 240 mg every 2 weeks in 4) and 7 (4.5%) had successful de-escalation (120 mg every 3 weeks in 4 and 120 mg every 4 weeks in 3). Clinical indices, CRP levels and FC remained unchanged (Figure). Median SC-IFX levels significantly increased from baseline of 4.5 mug/ dl [range 2.6-9.2] to 14 mug/dl [range 9.5-16.2] at week 12 and 13.2 mug/ dl [range 10.4-19.7] at week 24. No factors (immunossupresor, body mass index, disease location) were associated with the increase of IFX trough levels. During 24 weeks of follow-up, 16 of the 78 patients (20.5%) stopped immunosuppressant treatment. The adverse events were recorded in 9 patients (5.8%), 4 (2.6%) were hospitalized and 4 (2.6%) had surgery (one of them for perianal disease). Nine patients (5.8%) stopped SC-IFX (1 primary failure, 2 loss of response, 4 adverse events, 1 voluntarily, and 1 surgery). Conclusion(s): The switch from IV to SC IFX maintains clinical remission safely in IBD patients, offers higher drug levels and a good patient acceptance. However, the significance of higher drug levels with SC-IFX requires further exploration.
ABSTRACT
Introduction: The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. Aims & Methods: Aims: The aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic;the outcomes among those under immunosuppressants/ biologics for IBD;the risk factors for contracting the infection and poor outcomes;and the impact of the infection after three-month followup. Methods: Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results: A total of 482 patients with COVID-19 from 63 centres were included: 247 Crohn's disease, 221 ulcerative colitis and 14 unclassified colitis;median age 52 years (IQR: 42-61), 48% women and 44% 1 comorbidity. Diagnosis was made by PCR: 62% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 18 patients died from COVID-19 (mortality:3.7%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Age 50 years (OR 2.09;95% CI:1.27-3.4;p=0.004), 1 comorbidities (OR 2.28;95% CI:1.4-3.6;p=0.001), and systemic steroids <3 months before infection (OR 1.3;95%CI:1-1.6;p= 0.003), were risk factors for hospitalisation due to COVID-19. A Charlson score 2 (OR 5.4;95%CI:1.5-20.1;p=0.01) was associated with ICU admission. Age 60 years (OR 7.1;95%CI:1.8-27.4;p=0.004) and having 2 comorbidities (OR 3.9;95% CI:1.3-11.6;p=0.01) were risk factors for COVID- 19 related death. Conclusion: IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients.