P336. The effect of granulocyte and monocyte adsorption for Crohn's disease patients with loss of response or adverse events for anti‑TNF‑α therapy
K. Koji1, F. Ken1, M. Takayuki1
1Division of Lower Gastoenterology, Department of Internal Medicine, Nishinomiya, Japan
Background: Dysregulated peripheral immune profile is known to have an important role in the initiation and perpetuation of Crohn's disease (CD) and recently, anti-cytokine therapy with biologics has been recognized as a major therapeutic option for CD, which is refractory to conventional medications. In Japan, infliximab (IFX) and adalimumab (ADA) have recently become available for clinical application. These biologics have been associated with a significant improvement of patients' quality of life. However, it has been recognized that many patients who initially respond well to IFX or ADA subsequently become refractory or intolerant to these biologics. In such cases, we have been administering corticosteroid or immunosuppressant.
Methods: We hypothesized that therapeutic granulocyte and monocyte adsorption (GMA) as an extracorporeal haemoadsorption, which can eliminate elevated and activated leucocytes of the myeloid linage might be effective in CD patient refractory to anti-TNF‑α therapy. Subjects were 25 CD patients with an average CD activity index (CDAI) of 242.71 and CD duration of 8.5 years. And the average of simple endoscopic score for Crohn's disease (SES-CD) was 15.07. The 11 patients had lost response to anti-TNF‑α therapy, and 4 patients had developed severe adverse reactions to anti-TNF‑α therapy. We applied 5–10, once a week GMA sessions instead of IFX for remission induction. Three patients who had achieved remission with ADA received one GMA session every two weeks as maintenance therapy. Similarly, 4 patients who were receiving scheduled maintenance IFX at 8 weeks intervals received 3–4 weekly GMA sessions due to a rise in their CDAI scores while under maintenance IFX therapy.
Results: Nineteen of 25 patients who had lost response to IFX or ADA responded well to GMA with a significant fall in CDAI scores and SES-CD scores (P < 0.05). Four patients could discontinue prednisone and IFX. Further, IFX and GMA combination therapy has associated with a sustained clinical remission without experiencing side effects or the need to shorten the interval or increase the dose of IFX. Patients who received GMA in combination with IFX developed no adverse side effect.
Conclusions: Anti-TNF‑α therapy appears to induce and maintain remission of CD, but following repeated administration, many patients lose response or develop severe side effects. GMA is safe and by selectively depleting elevated/activated leucocytes could be an effective adjunct therapy to enhance the clinical benefit of IFX.