Long-term follow-up of patients treated with infliximab (anti-TNFa antibody) in clinical trials
2000; Elsevier BV; Volume: 118; Issue: 4 Linguagem: Inglês
10.1016/s0016-5085(00)84399-1
ISSN1528-0012
AutoresStephen B. Hanauer, T Schaible, Kimberly L. DeWoody, P Marsters, Marilyn Peltier, Karen Dittrich, Gregory R. Harriman,
Tópico(s)Neutrophil, Myeloperoxidase and Oxidative Mechanisms
ResumoNeutrophils playa central role in host defence, by killing and eliminating micro-organisms through production of reactive oxygen species.Defective neutrophil function has been related to incomplete bacterial clearance and chronicity of infections.G-CSF stimulates granulopoesis, increases neutrophil activity and mediates anti-inflammatory effects.Recombinant human (rh) G-CSF promoted healing of CD-like intestinal lesions from patients with chronic granulomatous-or glycogen storage disease lb.Aim: We performed a prospective, open pilot study to investigate the safety and efficacy of rhG-CSF for the treatment of severe endoscopic recurrence in CD.Patients & Methods: Five clinically inactive CD patients (CDAI<150) with severe endoscopic ileitis (Rutgeert's score i3-i4) who had undergone curative surgery within the past year received 300fLg rhG-CSF (Neupogen'", Amgen) subcutaneously, 3 times weekly for a total of 12 weeks.No concomitant therapy was allowed except continuation of 5-aminosalicylates (2-3g/d) without change of dose.Clinical and laboratory safety data as well as disease activity (CDAI) were recorded at each visit (day 0, dl, d2, week I, w2, w4, w8, wI2).Colonoscopy, intestinal permeability and quality of life (IBDQ) were assessed before and after treatment.Primary outcome was complete mucosal healing (Rutgeert s score iO).Results: All patients completed the protocol.Mild bone pain occured in a single patient, transient headache (WHO grade II) in another resolved after reducing G-CSF dosage to 150fLg.Neutrophil counts were markedly elevated after the first injection [day 0: median 4.4 Gil (range 3.7-7.5)vs. day 1: 23.3 (19.3-33.3)p<O.OI] and remained increased throughout drug administration [day 2: 13.0 (9.9-14.4)p<O.OI and week 1: 25.2 (24.3-36.5)p<O.01].Entire mucosal healing was achieved in one patient, whereas no endoscopic changes were observed in the others.One patient showed the closure of a longstanding rectovaginal fistula..7],intestinal permeability [wI2: 0.012 (0.008-0.026) p=0.2],IBDQ [wI2: 210 (172-222) p=0.2] and CRP [wI2: 0.7 mg/dl (0.5-1.4) p=l] remained normal and were not significantly different to baseline.Conclusion: These data indicate that rhG-CSF is safe, well tolerated and may provide some efficacy in CD.The potential role of rhG-CSF for treatment of postoperative recurrence and fistulas needs to be further addressed in controlled trials.
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