Wk 10 IBD therapeutics Lewis

When are biologics 1st line?

Patients with moderate-severe severity

When is the window of opportunity for improving IBD?

Between diagnosis and early disease

What are counseling points for Sulfasalazine?

DR tablets have less GI intolerance, cause urine/skin to turn yellow/orange, caution in pts with G6PD deficiency, reduces sperm counts/ fertility in males takes folate

When is sulfasalazine contraindicated?

Sulfa or salicylic allergy

What is an example of an aminosalicylate?

Sulfasalazine

What are examples of 5-aminosalicylates?

Meslamine (oral): Asacol, Rowsa (enema), Cansa (supp), Balsalazide (Colazal, Olsalazine (Diptenum)

When should Apriso (Mesalamine oral) not be used?

Don’t use with antacids or PKU

When are aminosalicylates used?

Use in mild UC, does not work well for CD (except pentasa)

When are corticosteroids used?

No role in maintenance of IBD. (suppresses acute inflammation)

What are side effects of corticosteroids?

Cushing’s syndrome, osteoporosis, retardation of growth, thinning of skin, immunosuppression, cataracts + glaucoma, oedema, suppression of pituitary axis, teratogenic, emotional disturbances, raised BP, obesity, increased body hair growth, raised blood pressure, stomach ulcers

What are counseling points for budesonide?

Used as bridge therapy, avoid CYP3A4 inhibitors, separate oral budesonide 2 hours from antacids, minimal systemic absorption

What are the forms of budesonide?

Entocort (PO) for CD, Uceris (PO or rectal foam) for UC.

What are examples of immunomudlators?

Azathioprine, mercaptopurine, methotrexate, cyclosporine

What are ADRs of immunomodulators?

Immunosuppression, no live vaccines, risk of infection/ lymphoma. Monitor LFTs, kidney function, CBC

What route are azthioprine, mercaptopurine given?

Oral

What are counseling points of Azathioprine, Mercaptopurine?

Check TPMT activity (if low more risk for myleosuppression), ADRs (bone marrow suppression, pancreatitis). BBW malignancy. No live vaccines. Takes weeks -1 year to see results.

What are the routes of metabolism for Azathioprine (prodrug for 6-mercaptopurine)?

6-MP + TPMT → 6-methyl MP (hepatotoxic). 6-MP + XO → 6-thiouric acid (inactive). 6-MP + HGPRT → 6-thioinosinic acid (myelosuppression)

What are examples of xanthine oxidase inhibitors which interact with AZA and 6-MP?

Allopurinol, Febuxostat

What should be done if 6-MP or AZA is given with allopurinol?

Reduce dose of 6-MP or AZA by 25%

Can febuxostat be given with AZA and 6-MP?

No (contraindicated)

What routes are methotrexate given?

IM, SQ, PO weekly

What are counseling points for methotrexate?

Contraindicated in pregnancy & breastfeeding. NSAIDs, phenytoin, cipro, penicillins, probenecid, amiodarone, & PPIS inhibit excretion. Don’t give live vaccines. Can cause bone marrow suppression & pancreatitis. Obtain baseline tests & chest x-ray

What route is cyclosporine given?

IV

What are counseling points for cyclosporine?

DDI w/ all statins, CI w/ simva & ptavastatin. 10mg atorvastatin, 5mg rosuvastatin. Neurotoxicity & nephrotoxicity. Monitor cyclosporine levels 300-400ng/mL. No live vaccines

When is AZA-6MP given?

Used for maintenance of remission of CD & UC. Can be used for induction if combo w/ TNFa

When is MTX used?

Used for maintenance of remission in CD

When is cyclosporine used?

Used for induction of remission for UC

What antibiotics can be used as adjuncts?

Metronidazole, Ciprofloxacin, Rifamycin

What TNF-a inhibitors are used?

Infliximab (Remicade) IV, Adalimumab (Humira) SQ, Golimumab (SImponi) SQ, Certolizumab (Cimzia) SQ

When are TNF-a inhibitors used?

Induction of remission and maintenance therapy. 1st line

Which TNF-a can be stored at room temp for 14 days?

Adalimumab

What are counseling points for Infliximab (Remicade)

Pre medicate w/ antihistamines, acetaminophen, and CS to reduce rsl of infusion rxns. Monitor BP & HR every 2-10 min until normal

What are examples of live vaccines?

MMR, Varicella, rotavirus, yellow fever

What should be tested for before staring TNF-a?

TB, hepatitis

What should be monitored in TNF-A inhibitors?

Antidrug antibodies, derm screening, eye screening

What should not be given in maintenance of remission?

Corticosteroids

What is HSTCL?

Hepatosplenic T-cell lymphoma (HSTCL). Most common in men < 35. Highest risk in TNF-A + thiopurines

What should be done if loss of response to TNF-a?

Low drug levels + antibodies (switch to alternative TNF), low drug levels - antibodies (dose escalation or shortened interval), normal drug level - antibodies (switch to another class)

Which biologics have a risk for PML?

Vedolizumab (Entyvio) gut selective & Natializumab (Tysabri) must have negative John Cunningham antibody

Which biologics have a RPLS risk?

Ustekinumab (Stelara), Risankizumab (Skyrizi), Omvoh (Mirikizumab), Tremfya (auselkumab)

Which biologics can cause thrombosis? (don’t initiate if low lymphocytes or hemoglobin)

Tofacitinib (Xejanz), Upadactitinib (Rinvoq)

For mild disease what should be started?

Step up approach (steroids or ASA)

For moderate-severe disease what should be started?

Top-down approach (biologic and/ or immunomodulator therapy)