Promising Biologic for Eosinophilic Esophagitis

A recent study (I Hirano et al. Gastroenterol 2019; 156: 592-603) showed that RPC4046, a monoclonal antibody against IL13 is a promising agent for eosinophilic esophagitis. This multicenter double-blind study with 99 adults compared RPC4046 at doses of either 180 mg or 360 mg to placebo for 16 weeks.  Endoscopy was performed at baseline and at 16 weeks.  The study population included a high number who were considered steroid-refractory and excluded patients who were responsive to proton pump inhibitors. The study drug was administered initially as an IV load followed by weekly subcutaneous injections.

Key findings:

  • Mean changes in esophageal eosinophil count dropped by 94.8 in patients receiving 180 mg dosing and 99.9 in patients receiving 360 mg dosing.  In contrast, placebo-treated patients had a meager reduction of 4.4.
  • In this phase II study, there were no serious safety issues identified
  • There were no significant changes relative to placebo in dysphagia symptoms using the DSD (dysphagia symptom diary) composite score. Though there was improvement in global PRO measures compared to placebo.

There is an associated editorial (pg 545) explains the need for better therapies.  While both dietary therapies and topical steroids are likely effective in >70%, dietary therapy is plagued by problems with long-term adherence and there may become less effective with longer-term administration.

My take: Particularly for patients with refractory EoE, newer therapies are needed.  Given the chronic nature of EoE, cost of new treatments could be another hurdle.

Related blog posts:

Assessing and discussing risk of lymphoma in IBD

A recent article has shown that the absolute lymphoma risk from medications in children and young adults with IBD is quite low (Inflamm Bowel Dis 2012; 18: 838-43).

In this single center study from 1979-2008, 1374 pediatric IBD patients had charts reviewed to determine whether lymphoma developed.  In total, two male patients who had received thiopurines developed lymphoma (one Hodgkin, one anaplastic large cell) in 6624 patient-years of follow-up.  Both patients are alive after chemotherapy.  Mean follow-up was 4.8 years per patient.  The absolute lymphoma incidence rate was 3 per 10,000 patient-years; after thiopurine exposure, the rate was 4.5 per 10,000 patient-years compared to an expected 0.58 per 10,000 patient-years.

In this study, 22% of the patients had received TNF inhibitors.  None developed lymphoma.  The risk of biologics could not be fully assessed due to a limited study period: 713 person-years taking the medication.

The risk of thiopurine-associated lymphoma was similar to previous studies but did not reach statistical significance.  As related in other studies, the risk of biologic agents, like Remicade, Humira, and Cimzia, is heavily influenced by whether patients had also received immunomodulators.

One useful way to try to convey this risk has been with diagrams.  One useful diagram is a palette of one thousand people or of 10,000 people showing the absolute risk and one showing the risk for other complications like infection.  You can make your own by going to the following link:

Download Communication Tools

RiskComm

Additional references/blog entries:

Only one chance to make first impression

Biologics | Living Longer | Arthritis Today Magazine -From Arthritis magazine: biologics improve survival in Rheumatoid arthritis