Vedolizumab Should Be Used Before Anti-TNFs For Moderate To Severe IBD

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Presentation transcript:

Vedolizumab Should Be Used Before Anti-TNFs For Moderate To Severe IBD William J. Sandborn, MD Professor and Chief, Division of Gastroenterology Director, UCSD IBD Center

How to decide? Risks and Benefits Vedolizumab Infliximab CTZ ADA GOL 1st line Bioloigc Vedolizumab Infliximab ADA CTZ GOL Risks and Benefits

Feagan BG. NEJM 2013 Rutgeerts P. NEJM 2005 Sandborn WJ Gastro 2012 Sandborn WJ Gastro 2014

Efficacy of induction therapy in biologic naïve Danese S. Annals 2014

Feagan BG. NEJM 2013 Rutgeerts P. NEJM 2005 Sandborn WJ Gastro 2012 Sandborn WJ Gastro 2014

Efficacy as first line agent Good efficacy for Induction and Maintanence therapy in UC Good efficacy for Induction and Maintanence therapy in UC Vedolizumab Anti-TNF

Sandborn WJ. NEJM 2013 Targan et al. NEJM 1997 Hanauer et al. Gastro 2006 Sandborn WJ. NEJM 2007

Sands BE. Gastro 2014

Sandborn WJ. NEJM 2013 Sandborn WJ. NEJM 2007 Colombel et al. Gastro 2007 Hanauer et al. Lancet 2002

Efficacy as first line agent Good efficacy for Induction and Maintanence therapy in UC and CD Good efficacy for Induction and Maintanence therapy in UC and CD Vedolizumab Anti-TNF

Feagan BG. NEJM 2013 Sandborn WJ NEJM 2013

Feagan BG. NEJM 2013 Sandborn WJ NEJM 2013

Outcomes with anti-TNF in biologic exposed Efficacy of subcutaneous biologics impacted by prior biologic exposure Impact of prior biologic exposure on efficacy of Infliximab less clear Chaparro M WJG 2012

Efficacy as first line agent Good efficacy for Induction and Maintanence therapy in UC and CD Prior biologics WILL impact efficacy Good efficacy for Induction and Maintanence therapy in UC and CD Prior biologics MAY impact efficacy Vedolizumab Anti-TNF

Safety: Is Vedolizumab Gut Selective? No peripheral blood lymphocytosis No protective effect in primate model of MS (EAE) No inversion of CD4\CD8 ratio in CSF of humans Clinical data – no cases of PML observed Preservation of systemic humoral responses to T cell dependent antigens with modest impairment to oral antigen (vaccine study)

Hepatitis B Surface Antibody (HbsAb) Concentration Through Day 74* Wyant T A. et al. Gut 2014

Serum IgA Response to Oral Cholera Vaccine Through Day 74* *Dukoral Population Wyant T A. et al. Gut 2014

Black Box Warnings Vedolizumab Ant-TNF None Serious Infections Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. Malignancy Lymphoma and other malignancies Fatal hepatosplenic T-cell lymphoma

Comparison of Lymphoma (Vedolizumab, Natalizumab) Lymphoma Expected Rate (General Population) 2/10,000 PYF Anti-TNF therapy 6/10,000 PYF Anti-integrins (Vedolizumab, Natalizumab) 3/10,000 PYF Dulai PS, Siegel CA. GCNA 2014

Dermatology (psoriasis) Other Risks Vedolizumab Anti-TNF therapy Serious Infection - +/- Opportunistic + Demyelinating Autoimmune (SLE, vasculitis) Dermatology (psoriasis) Cardiac (CHF) Pulmonary (Sarcoidosis, ILD) Caveat: most new drugs have additional toxicities identified during post-marketing surveillance Kopylov U. GCNA 2014 Feuerstein JD. GCNA 2014

Risks of Therapy Anti-TNF Vedolizumab Good efficacy for Induction and Maintanence therapy in UC and CD Prior biologics WILL impact efficacy Low risk of malignancy, driven by IMM No signal for systemtic risks Good efficacy for Induction and Maintanence therapy in UC and CD Prior biologics MAY impact efficacy Low risk of malignancy, driven by IMM Systemtic risks well established Vedolizumab Anti-TNF

Which one would you choose? Drug A Drug B Efficacy similar Lower if used second Gut selective with no signal of other risks Efficacy similar Unclear if lower as 2nd line Clear association to other systemic risks