Medications should never be stopped for Crohn’s disease patients in remission Thomas Ullman, M.D. Chief Medical Officer Mount Sinai Doctors Faculty Practice The Mount Sinai School of Medicine New York, NY

Reasons to Start Immunomodulators and Anti-TNF’s in Crohn’s Disease Steroid-dependent/refractory disease Penetrating/fistulizing disease Symptomatic disease Minimize mucosal inflammation Prevention of: Surgery Hospitalization Work/school absenteeism Improvement of quality of life (QoL)

Reasons to Discontinue Reasons to Continue Minimize complications Minimize steroid exposure Maintain remission Maintain quality of life Avoid potential toxicity Infections Malignancy Cost Inconvenience Reasons to Discontinue

What do the data tell us Results from the literature for the following Stopping thiopurines as monotherapy: bad idea Stopping thiopurines in combination therapy (thiopurine + anti-TNF): sort of bad idea Stopping anti-TNF’s in monotherapy: really bad idea Stopping anti-TNF’s in combination therapy (thiopurine + anti-TNF): bad idea Results from the literature not yet there Stopping methotrexate as mono- or combo-therapy Stopping natalizumab/vedolizumab

Stopping Thiopurines in Monotherapy

Randomized Trial of AZA vs Randomized Trial of AZA vs. PBO in Stable AZA using patients in remission >42 months in remission (CDAI<150) Oral prednisone < 10 mg/d No biologics, budesonide, TPN, surgery, rectal steroids, antibiotics for Crohn’s, aminosalicylates for 6 months 63 patients Randomized 1:1, double blind 40 AZA; 43 PBO Non-inferiority study Proportion with relapse in 18 months CDAI >250 or CDAI 150-250 for 3 consecutive weeks and increase >75 from baseline Lemann, Gastro 2005; 128:1812-1818

AZA withdrawal wasn’t non-inferior: Continue with While K-M differences not statistically different, the difference was Lemann, Gastro 2005; 128:1812-1818

Stopping Thiopurine in Combination Therapy

Remission after IMM Discontinuation in Combination Therapy Van Assche, Gastro 2008

Changes in CRP and IFX Levels? Van Assche, Gastro 2008

Stopping Anti-TNF in Combination Therapy

STORI trial 115 patients in remssion on IFX for mean 2.2 years 96 on AZA/6MP, 19 on MTX 44% relapse at 1 year Louis et al, Gastro 2012; 142:63-70

Cohort of Canadian Patients who voluntarily withdrew IFX: 50% relapse at 477 days Waugh, APT, 2010

Endoscopic Recurrence Among patients in surgical remission: “Deepest Remission,” as phrased by first author--DON’T STOP 5-year f/u of post-op infliximab (IFX) vs placebo in post-operative recurrence (Gastro 2009) All subjects offered open label IFX and followed for additional 4 years Outcomes Endoscopic Recurrence (Rutgeerts Score i2 or greater at year 5) Surgical Recurrence (need for re-operation) Initial Group Follow Up Group n Endoscopic Recurrence Surgical Recurrence IFX Continued IFX 7 0 of 7 (0%) Stopped IFX 5 4 of 5 (80%) Placebo Started IFX 10 3 of 10 (30%) Continued off IFX 2 2 of 2 (100%)

What do the data tell us Results from the literature for the following Stopping thiopurines as monotherapy: bad idea Stopping thiopurines in combination therapy (thiopurine + anti-TNF): sort of bad idea Stopping anti-TNF’s in monotherapy: really bad idea Stopping anti-TNF’s in combination therapy (thiopurine + anti-TNF): bad idea Results from the literature not yet there Stopping methotrexate as mono- or combo-therapy Stopping natalizumab/vedolizumab

“If It Ain’t Broke Don’t Fix It” Turns out this is not a Yogi-ism, but was popularized by Jimmy Carter’s first OMB Director: Bert Lance

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