Author(s) Jennifer labas , FNP-BC, RN, MSN

1. November 2018 Managing Severe Ulcerative Colitis in the Hospital Setting – Salvage Therapy with Cyclosporine Bridge Author(s) Jennifer labas, FNP-BC, RN, MSN reviewed by the Crohn’s & Colitis Foundation’s Nurse & Advanced Practice Committee

2. Instructions • To begin, please enter into “Presentation mode” to enable full interactivity of case and questions. (Click “slide show” tab)When you see words or phrases that are underlined click on the underlined word and this will take you to the next screen. To continue the presentation make sure you click back in the bottom left corner.

3. Objectives • Audience will understand the clinical situation of ulcerative colitis, in which salvage therapy is considered. • Audience will understand induction of salvage therapy as a bridge to maintenance medical options. • Audience will understand what it means to achieve remission with salvage therapy, as well as the importance of compliance with follow-up care.

4. Introduction/Background • 25 y.o. male diagnosed with UC at age 15 when he developed diarrhea w/blood/urgency • Failure of • Mesalamine • Intermittent IV/PO steroids • Dual therapy w/Azathioprine + Adalimumab (including dose escalation to weekly dosing) • Infliximab (s/p 2 loading doses) →initial improvement after 2nd, then worsened • Admitted May 2017

5. Review of Systems (ROS) • No headaches, or oral ulcers • +Fatigue, no dizziness with standing • No skin rashes • Bilateral knee arthralgias consistent with active disease • 10-15 bloody BMs/day, no response to po Prednisone 40mg daily

6. Physical Exam • Blood pressure 110/72, pulse 67, temperature 36.4 °C (97.5 °F), temperature source Tympanic, resp. rate 15, weight 56.8 kg (125 lb 3.5 oz), SpO2 100 %. • The patient is alert and oriented x3, in no acute distress. • HEENT: Extraocular motion intact. Pupils equal, round and reactive to light. Oropharynx is clear. Sclerae are nonicteric. Neck: There is no lymphadenopathy; the thyroid is not palpable. • CARDIAC: RRR, normal S1, S2.No murmurs, rubs or gallops. • PULMONARY: Clear bilaterally to auscultation and percussion. • BACK: No CVA tenderness. • ABDOMEN: Soft, non-tender, non-distended. Bowel sounds are present. No obvious hepatomegaly, splenomegaly, or masses. No hernias or ascites. • PERIANAL: Examination is deferred. • GENITALS: Examination deferred. • LYMPHATICS: No palpable nodes in the neck. • MUSCULOSKELETAL: Normal gait and station, digits and nails. Extremities are all normal without edema. • SKIN: Anicteric. No rashes • NEUROLOGICAL: Cranial nerves intact. • PSYCHIATRIC: Appropriate judgement and insight, oriented to time, place and person, has normal recent and remote memory, and appropriate mood and affect.

7. Work Up – Obtain baseline flex sig • Flex sig with moderate inflammation was found from the anus to the sigmoid colon 2nd to pan UC • .

8. Previous Workup • BP: Normotensive • Lipid Panel: total cholesterol 148 • CMP: Magnesium 2.2, Creatinine 0.6 • Quantifuron Gold/Hepatitis B serologies: Negative • CBC: WBC 6.7, Hgb 12.0 • CMV PCR: Negative • GI Panel: Negative (initially) • CRP: 12

9. Do you have red flags/cause for concern based on physical exam & previous workup? • Is patient hypertensive? • Is patient cholesterol < 100? • Does patient have a baseline leukocytosis? • Does patient have a baseline anemia? • Does patient have normal electrolytes? • Does patient have normal creatinine? • Baseline KUB?

10. Do you have a Differential Diagnosis? • Is this CMV (cytomegalovirus)? • Flex sig for tissue CMV PCR and serum CMV PCR • If +, initially treat with IV Ganciclovir 5mg/kg IV BID x 3 weeks, then change to Valcyte 900 mg po BID until negative tissue/serum • Consult Infectious Disease for duration (likely want negative tissue biopsy and negative serum PCRs prior to cessation of therapy as immunosuppressed) • Assess for improvement if UC needs to be treated separately • Is this c.diff (clostridium difficile)? • GI panel (tests for 22 different GI bacteria/viruses) • If positive for c.diff, initiate Vancomycin 125mg po QID • Assess for improvement if UC needs to be treated separately

11. What is your plan of care? • Initiate IV Cyclosporine at 4mg/kg • Goal trough 300-400 • First trough checked 48 hours post infusion initiation • MUST BE CONTINUOUS INFUSION FOR RELIABLE TROUGH • Cannot be disconnected for shower, or for prolonged time as can drop level • If patient loses IV access, RN must immediately notify team • Given in conjunction with IV Solumedrol • Bactrim PJP prophylaxis (1DS q MWF) • SURGICAL CONSULT – NEVER LEAVE THIS DISCUSSION UNTIL THE LAST MINUTE – PATIENT NEEDS TIME TO PROCESS AND UNDERSTAND IF SALAVGE THERAPY FAILS, COLECTOMY IS ONLY REMAINING OPTION

12. Daily Evaluation • CRP 12 initially → down to < 3 with gradual improvement of symptoms • Day #6, CRP bump to 14→26→34 • C.diff rechecked (initially negative) • Now positive • PO Vancomycin initiated • CRP decreased from 34 to 7 in 24 hours • Initiated outpatient Vedolizumab prior authorization • Discharged home on: • BID Cyclosporine dosing (ex: 300mg IV bag = 300mg po BID) • Prednisone 40mg po daily • Bactrim 1 DS q MWF • Azathioprine 150mg daily • Vancomycin 125mg po QID x 14 days (for c.diff)

13. So How Did He Do Post Discharge? • Patient successfully weaned off Prednisone after Vedolizumab initiation in June 2017 (maintenance troughs decrease to 200-300) • Azathioprine dose optimized to 200mg po daily, based on metabolite levels • Successfully weaned off Cyclosporine August 2017 (after creatinine bumped from 0.6 to 1.2) • Most recent clinic visit February 2017 • Completed college • Relocated to Chicago • Got engaged • Starting a new job in full remission • Due for repeat colonoscopy

14. Summary • Cyclosporine is a very effective salvage therapy, once patient has exhausted all standard induction modalities. • It is only to be used as a bridge therapy, for no longer duration than 3 months, given nephrotoxicity risk. • Follow-up is EXTREMELY important given effects Cyclosporine can have on blood pressure, electrolytes, and kidneys. • Cyclosporine is NOT an option for patients who are noncompliant, given above risks. In this event colectomy would be recommended should no additional medical options be available.