Published in:
01-07-2019 | Infliximab | Original Article
Efficacy of Infliximab in Crohn’s Disease Patients with Prior Primary-Nonresponse to Tumor Necrosis Factor Antagonists
Published in: Digestive Diseases and Sciences | Issue 7/2019
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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.