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Dig Dis Sci. 2019 Feb 28. doi: 10.1007/s10620-019-05490-0. [Epub ahead of print]

Efficacy of Infliximab in Crohn's Disease Patients with Prior Primary-Nonresponse to Tumor Necrosis Factor Antagonists.

Author information

1
Division of Gastroenterology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA.
2
Division of Gastroenterology, University of Washington, 1959 NE Pacific Street, Seattle, WA, 98195, USA. ScottL@medicine.washington.edu.

Abstract

BACKGROUND:

Tumor necrosis factor antagonists (TNFs) are effective for moderate-severe Crohn's disease (CD). Approximately one-third of patients have primary-nonresponse to TNFs, which is reported to predict worse response to subsequent TNF therapy. However, this is based on treatment with subcutaneously (SC) administered, fixed-dose TNFs after failure of intravenously (IV) administered, weight-based TNFs. No study has specifically assessed the clinical and endoscopic effectiveness of IV TNFs following primary-nonresponse to SC TNFs. We hypothesize that IV, weight-based TNF dosing offers advantages over SC, fixed-dose TNFs and may be effective despite primary-nonresponse to previous SC fixed-dose TNFs.

METHODS:

This retrospective cohort study identified patients with moderate-severe CD with primary-nonresponse to one or more SC TNFs who subsequently received the IV TNF, infliximab for ≥ 12 weeks. We described baseline characteristics, and clinical, endoscopic and biochemical response to therapy.

RESULTS:

Key characteristics of 17 patients are described in Table 1. After ≥ 12 weeks of infliximab, 11 of 15 (73.3%) patients with clinical data reported clinical response and remission. Of 11 patients with endoscopic data, restaging colonoscopy revealed mucosal improvement in seven (63.6%) patients. Of these, five (45.5%) had endoscopic remission and three (27.3%) had mucosal healing. Table 1 Baseline characteristics of CD patients with primary-nonresponse to subcutaneous (SC) tumor necrosis antagonists (TNF), subsequently treated with intravenous (IV) TNF therapy Characteristics N 17 Mean age, years (range) 37.5 (18-67) Mean BMI, kg/m2 (range) 26.6 (17.8-40.6) Mean albumin prior to infliximab, g/dL (range) RR: 3.5-5.2 g/dL 3.57 (2.5-4.2) Female sex [n (%)] 7 (41.2) Tobacco use [n (%)]  Never 15 (88.2)  Former 1 (5.88)  Current 1 (5.88) Age at diagnosis [n (%)]  Less than 17 2 (11.8)  17-40 11 (64.7)  Over 40 4 (23.5) Mean disease duration, yrs (range) 7.76 (1-24) Disease extent [n (%)]  Ileal 2 (11.8)  Colonic 5 (29.4)  Ileocolonic 10 (64.7) Disease behavior [n (%)]  Nonstenosing, nonpenetrating 10 (58.8)  Stenosing 3 (17.6)  Penetrating 2 (11.8)  Stenosing and penetrating 2 (11.8) History of gastrointestinal surgery [n (%)] 4 (23.5)  Ileocecal resection (n) 2  Hemicolectomy (n) 2 Prior therapy [n (%)]  IV corticosteroids 3 (17.6)  Oral corticosteroids 14 (82.4)  5-ASA 12 (70.6)  Thiopurine 14 (82.4)  Methotrexate 10 (58.8) Prior biologic therapy  Adalimumab only 12 (70.6)  Certolizumab pegol only 2 (11.8)  Adalimumab and certolizumab pegol 2 (11.8)  Adalimumab, certolizumab pegol and golimumab 1 (5.88) Dose escalation of prior SC TNF [n (%)]  Adalimumab 9 (52.9)  Certolizumab pegol 0 (0.0)  Golimumab 0 (0.0) During infliximab, concomitant therapy [n (%)]  Immunomodulator 13 (76.5)  Corticosteroid 5 (29.4) CONCLUSIONS: Patients with moderate-severe CD with prior primary-nonresponse to SC, fixed-dose TNFs, subsequently treated with IV, weight-based TNF have high rates of clinical and endoscopic response and remission. Therefore, despite primary-nonresponse to SC TNFs, patients may benefit from IV TNF therapy and may not require a change to a different class of biologic therapy.

KEYWORDS:

Crohn’s disease; Infliximab; Primary-nonresponse; Tumor necrosis factor antagonist

PMID:
30815825
DOI:
10.1007/s10620-019-05490-0

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