Background Behçet's disease (BD) is a multisystem disease characterized by mucocutaneous, ocular, neurologic, vascular, or gastrointestinal manifestations. Involvement of the neuronal (NBD) and vascular (VBD) systems and intestinal tract (intestinal BD) is rare, although such cases tend to have a poor prognosis.
Objectives We conducted a prospective multicenter clinical trial to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy (ClinicalTrials.gov, NCT01532570).
Methods IFX at 5 mg/kg was administered to 18 patients (3 NBD [2 acute and 1 chronic progressive], 4 VBD, and 11 intestinal BD) at Weeks 0, 2, and 6 and every 8 weeks thereafter until Week 46. In patients who showed inadequate responses to IFX after Week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain MRI, CT angiography, positron emission tomography, cerebrospinal fluid, CRP, or ESR), exploring the percentage of complete responders at Week 30 as the primary endpoint.
Results The percentage of complete responders was 61% (11/18) at both Weeks 14 and 30 and remained the same until Week 54. By BD type, the percentage of complete responders at Week 30 was 33% (1/3) among NBD patients, 100% (4/4) among VBD patients, and 55% (6/11) among intestinal BD patients. In acute NBD patients, IFX lowered the cell count and IL-6 concentrations in the cerebrospinal fluid and inhibited the onset of attacks. In a chronic progressive NBD patient, IFX lowered cerebrospinal fluid IL-6 concentrations along with inhibition of progression of clinical symptoms and brainstem atrophy. VBD patients showed improvement in clinical symptoms at an early stage (Week 2) with reductions in serum CRP levels and ESR. Accordingly, positron emission tomography/CT imaging studies showed reversal of inflammatory changes in three of the four VBD patients. Intestinal BD patients also showed improvements in clinical symptoms along with decrease in serum CRP levels after Week 2. Consistently, scarring or healing of the principal intestinal ulcer in each patient was found in more than 80% of these patients after Week 14. Irrespective of the type of BD, all patients achieved improvements in visual analogue scale and Short Form 36 scores, leading to the dose reduction or complete withdrawal of steroids. IFX dose was increased to 10 mg/kg in three intestinal BD patients, resulting in improvement of clinical symptoms, CRP level, and visual analogue scale score. Safety and pharmacokinetics profiles were comparable to those in patients with rheumatoid arthritis or Crohn's disease.
Conclusions The results demonstrate that IFX is effective and well tolerated in the treatment of recalcitrant NBD, VBD, and intestinal BD with poor response or intolerance to conventional therapy. IFX may therefore represent a promising new therapeutic option for use in BD patients with these serious complications.
Disclosure of Interest Y. Ishigatsubo Grant/research support from: Astellas Pharma, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Kissei Pharmaceutical, Meiji Seika Pharmaceutical, Mochida Pharmaceutical, MSD, Nippon Shinyaku, Ono Pharmaceutical, Pfizer, Takeda Pharmaceutical, Teijin Pharmaceutical, Consultant for: Celgene K.K., Mitsubishi Tanabe Pharma, Speakers bureau: AbbVie, Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma, MSD, Santen Pharmaceutical, Takeda Pharmaceutical, S. Hirohata Grant/research support from: Astellas Pharma, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Pfizer, Takeda Pharmaceutical, Consultant for: Mitsubishi Tanabe Pharma, Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma, MSD, H. Kikuchi Consultant for: Mitsubishi Tanabe Pharma, Speakers bureau: Mitsubishi Tanabe Pharma, U. Tateishi Consultant for: Mitsubishi Tanabe Pharma, N. Sato Employee of: Mitsubishi Tanabe Pharma, K. Ozaki Employee of: Mitsubishi Tanabe Pharma, K. Kondou Employee of: Mitsubishi Tanabe Pharma, T. Hibi Grant/research support from: AbbVie G.K., Eisai, JIMRO, Zeria Pharmaceutical, Consultant for: Ajinomoto Pharmaceuticals, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Speakers bureau: AbbVie G.K., Eisai, JIMRO, Zeria Pharmaceutical, Mitsubishi Tanabe Pharma