Exam 4 lecture 2 Flashcards
Symptoms of mild/moderate active UC
4-6 stools per day
no fever
How is mild/moderate active UC grouped depending on where it is occuring? WHat is used to treat them?
Left sided disease- within reach of enemas
Proctitis- within reach of suppository
Extensive disease pancolitis- requires systemic tx
Should we use oral and/or topical ASAs for mild-moderate active UC
extensive disease- oral- ASA
left sided- topical mesalamine enema
proctitis- mesalamine suppository
Combo of oral and topical may be more effective for left sided/extensive disease
If orally treating Mild/moderate UC, Which drug is better tolerated?
Mesalamine derivatives better tolerated than sulfasalazine
What to do if pa tient is unresponsive to 5-ASA for mild/moderate active UC
Consider changing formulation (if on mesalamine, try sulfasalazine)
Or bump up the dose of the drug
remember combo therapy is more effective
alternative drug
What are alternate drugs we use for mild/moderate active UC if unresponsive to oral/topical ASA
CR budesonide (limit to 8-16 weeks)
PO corticosteroids (prednisone) for pts refractory to ASA
topical corticosteroids (foams, enemas, suppositories) (are effective for distal disease)
symptoms of mod/severe active UC
4-6 stools per day
blood/mucous in stool
Weightloss, lab abo=normalities (increase in ESR)
Tx of mod/severe active UC
5-ASA therapy possible for moderate, but not severe disease
Systemic corticosteroids (PO prednisone)
(for moderate use oral budesonide)
What is pts are not responsive to Corticosteroids/ASA or steroid dependent for moderate/severe
TNF-a inhibitors/biologics (potentially newer small molecules)
What are TNF inhibitors used for moderate-severe active UC? Anti integrins? IL 12-23 inhibitors? JAK inhibitors? SP1 inhibitors?
TNF- infliximab, adalimumab, golimumab
ANti-integrin- Vedolizumab
IL 12-23- ustekinumab, mirikizumab, risankizumab
JAK- upadactinib, tofactinib (black box warning for RA pts for CV events), only used if failed TNF inhibitors)
SP-1 ozanimod, estranimod
for moderate/severe active UC, can we use methotrexate for induction or maintenance? Is biologic monotherapy an option? Can we use thiopurine monotherapy for induction? maintenance?
It is suggested that we do not use methotrexate for induction or maintenance
Biologic monotherapy is an option.
Thiopurine monotherapy should not be using for induction. Can be used for maintenance
What combinations to use for moderate-severe active UC rather than monotherapy? Who mau choose biologic monotherapy?
Reccomendations for combining TNF antagonists, vedolizumab or usketinumab with thiopurines or methotrexate rather than monotherapy.
Patients with less severe disease or those who place relative value on minimizing ADRs vs maximizing efficacy may choose biologic monotherapy.
should we use biologics early or gradually stepup?
early use of biologics is recommended rather than gradual step up. Those with less severe disease who place a higher value on the safety of 5-ASA may prefer gradual step up
Is certolizumab approved for UC? What about golimumab?
certolizumab is NOT approved. Golimumab is approved
sx of severe fulminant UC? How is it treated?
6-10 BMs/day, blood present, systemic sx
consider NPO
Parenteral corticosteroids (methylprednisolone or hydrocortisone)
consider TNF-a inhibitors (infliximab) if unresponsive to IV steroids
for UC, what do we use as maintenance of remission
for mild, if we used ASA and they responded to mesalamine in induction, we can use that.
If on severe disease and they responded to induction by TNF inhibitor, we continue that. SO it depends on what we used to induce the tx
no role for corticosteroid in maintenance
Choices are mesalamine derivatives for mild disease or biologic/small molecule inhibitor for severe
What are some rules for maintenance of remission for ASAs
newer mesalamine derivatives are better tolerated than sulfasalazine
Use mesalamine enemas (if left sided disease) or suppositories (if proctitis)
May use combination of topical/systemic (more effective than either alone)
For maintenance of remission in UC, in patients who are steroid dependent or unresponsive to ASAs, what do we do?
Use azathioprine or 6-MP (slow to work-> 3-6 months)
maintenance of remission for UC patients that responded to TNF-a antagonists for induction? What about for patients who failed azathioprine?
TNF antagonist used for maintenance
Can also be used for pts who fail azathioprine
We can combine TNF antagonists with azathioprine to decrease ADAs
What are other biologics/ small molecule drugs that we can use to maintain remission and induction
Anti-integrin (vedolizumab)
IL 12-23 (ustekinumab, mirikizumab, risankizumab)
JAK inhibitor (upadactinib, tofactinib)
SP1 inhibitor (ozanimod, etrasimod)
Can we use mesalamine derivatives for CD?
Mesalamine derivatevies have minimal efficacy and are no longer recommended
symptoms of mild-moderate active CD? TX?
ambulatory, minimal systemic sx
CDAI<220
Sulfasalazine marginally effective for treating symptoms of milf/mod CD
controlled release budesonide to induce remission (8-16 wks)
Symptoms of mod/severe active CD? Tx options?
- failed treatment for mild/mod disease, systemic symptoms (fever, wt loss, abdominal pain/tenderness, anemia, vomiting, dirrhea)
CDAI- 220-450
systemic corticosteroid (PO prednisone)- treat until resolution of symptoms and resumption of wt gain, then do gradual steroid taper.
hospitalized pts may receive IV corticosteroids (methylprednisolone or hydrocortisone)
early biologic therapy (with or without immunomodulators) may be beneficial
Biologic therapy used for moderate-severe active CD
TNF-a antagonists
Are TNF-a antagonsists effective in moderate-severe active CD who have failed immunosuppressives (like thiopurines)? Steroid dependent pts?
Yes for both
What should TNF antagonists be combined with for moderate-severe active CD
Infliximab + AZA are efficacious together
it is suggested to use infliximab or adalimumab plus thiopurine for induction and maintenance over monotherapy in those native to biologics and immune modulators
What are otehr biologics used for moderate-severe active CD
- vedolizumab
- natalizumab (not recommended due to PML)
- IL12-23 antagonists (uske, risan)
JAK inhinitor (upadactinib) used if failed TNF inhibitor
is immunomodulator monotherapy recommended to induce remission for moderate-severe active CD? what about for maintenance
Immunomodulators like AZA and 6-MP monotherapy not recommended to induce remission (may help maintain remission after induced w steroids, may be steroid sparing)
May be used in maintenance
Can methotrexate be used as a monotherapy for induction in moderate/severe active CD? What about maintenance? cyclosporine? ASA/sulfasalazine?
mtx can be used for induction (especially in steroid dependent CD) and for maintenance of remission?
Cyclosporine only used in UC, ASA or sulfasalazine should not be used
symptoms of severe-fulminant CD
persistent s/s despite corticosteroids or biologic tx, cachexia (look like malnutritioned)
In patient tx
Consider NPO
CDAI>450
tx of severe/fulminant CD
parenteral corticosteroids (if no abscess)
(methylprednisolone or hydrocortisone) for 3-7 days that transition to PO
May consider infliximab (or other biologic) if not attempted prior
infliximab may be preferred if fulminant
maintenance of remission of CD
mild- not a lot works well. sulfasalazine/mesalamine may be used (def not in moderate/severe.
No role for systemic corticosteroids
Budesonide has minimal long term efficacy->not recommended for >4 months
AZA and 6-MP are effective (especially in steroid induced or infiliximab induced remission)
Methotrexate (alternative to AZA and 6-MP, esp in pts w initial resoinse to MTX), SQ only
TNF antagonists are often times first choice
How to use TNF-a antagonist for maintenance remission of CD
Use of infiliximab or adalimumab in combination with AZA or 6-MP in pts who are naive to biologics and immunomodulators
in moderate to severe disease, it is suggested early introduction with biologic +/- immunomodulator to be used vs delaying their use while trying 5-ASAs and/or corticosteroids
What are other biologics that can be used for maintenance of remission of CD
Anti integrin- vedolizumab
IL-12 and 23 antagonists- ustekinumab, risankizumab
(natalizumab not recommended)
SDOH and IBD
lower socioeconomic status may be associated with worse outcomes in IBD
What are symptoms of IBD that we should collect in PCP? What are social hx and drug hx that are pertinent? Labs?
Symptoms- abdominal pain, stool freq, hematochezia, extraintestinal sx
smoking
NSAIDS make them worse
Labs- CRP, ESR, WBC, fecal, c diff
Follow up of IBD?
Resolution of active disease symptoms (24-48 hrs for hospital pts, 7-14 days for outpatient)
monitor ADRs
Monitor for symptoms and toxicity/efficacy
What to use for mild ulcerative proctitis (left sided)? What drugs to dc
mesalamine derivaive (sulfasalazine, mesalamine)
use topical (suppository)
dc NSAIDs
if patient returns with ulcerative proctitis (left sided) after giving mesalamine suppository what drug do we give?
oral + topical combination works better.
Short course of budesonide could work too if that does not work
mesalamine better tolerated than sulfasalazine
treatment options for moderate/severe ulcerative proctitis (left sided)
systemic steroids
(maybe budesonide if not as severe, but prednisone if severe) until sx improve and taper off
Ensure ASA dose is optimized
Use enema
Short term and long term ADRs of steroids
SHort term- Hyperglycemia, gastritis, mood changes, elevated BP, difficulty sleping
Long term- Asceptic necrosis, cataracts, obesity, growth failure, HPA suppression, Osteoporosis
What type of substrate is budesonide (CYP)
3A
What to supplement patients on steroids?
Calcium (1000-1500mg/day) and vitamin D (800 U/day)
May consider bisphosphonates in pts w risks of osteoporosis and patients using > 3 months
Consider DEXA in pts >60
5-ASA ADRs? Drug interations?
common (>10%)- N/V/H
Olasalazine- Diarrhea (up to 25%)
drug i/a- antiplatelet/anticoags/NSAIDs-> May increase bleeding risk
PPIs, H2RAs, Antacids-> affect gastric PH and influence release of drug
how to treat severe UC
steroids- corticosteroids
Pain control and fluid control
Biologics should be used (TNF inhibitor probably, or small moleculed rugs approved for UC or using steroid for remission and using thiopurine for maintenance)
