Lecture 10 - Irritable Bowel Disease Flashcards
Left sided UC or CD refer to….
- Transverse colon
2. Proctitis
Right Sided UC or CD refers to….
- Terminal ileum
2. Ascending colon
fistulas and abscesses are likely to occur in CD due to the transmural nature of the disease….
True
Txm Goals of IBD
- relief symptoms
- improve quality of life
- maintaining adequate nutrition
- control/minimizing complications
- achieve + maintain remission
- achieve mucosal healing
Induction therapy
therapy to target acute disease flare
Maintenance remission
acute disease flare adequately managed
therapy to minimize further acute flares
defined as CDAI < 150 in studies
Treatment refractory
failed response to standard therapy
Steroid dependence vs resistance
steroids not a good long term solution*** never choose that option
intended for short period and then taper
non-pharm treatment options for IBD
Diet
Probiotics
Surgery = most common performed in UC pts, more benefit due to localized disease
Sulfasalazine Common Adverse effects
15% D/c use due to N/V, headache, Anorexia
Severe ADE: Hypersensitivity (sulfa), Hepatitis, Hemolytic anemias, Agranulocystosis, Pancreatitis
Sulfasalazine MOA:
composed of mesalamine + sulfapyridine.
sulfapyridine gets cleaved = sulfa allergy issues
Mesalamine SE
better than Sulfasalazine
GI: abdom pain, constipation
Hypersensitivity to mesalamine, aminosalicyates, salicylates
Nasopharyngitis
Mesalamine CI
GFR < 30ml/min
severe hepatic impairment
Mesalamine Typical response rate
2-4 weeks
Mesalamine/ASA formulation & Delivery
Mess sup - reach only around rector ~ 15cm
Mess enema - reach farther, distal colon
Branded mess - reach further up, oral time release Terminal ileum/Proximal colon
ASA HD -passed terminal ileum, almost ileum
Pentasa - all the way through to jejunum
Other Aminosalicylates + common SE
Olsalazine
Balsalazide
Common: osmotic diarrhea
Balsalazide: HA, abdominal pain
Corticosteroids SE + responso time
Shit load, which is why we dont use chronic
response in like 7-10 days
short term SE:
CNS: anxiety, insomnia, psychosis
Endo: Hyperglycemia
GI: weight gain, esophagitis, bleeding
Budesonide Common SE:
HA
Nausea
Acne
Respiratory infections
Other info Budesonide
Extensive 1st past metabolism, not approved for maintenance + long term management
Entocort EC = indicated for CD
Uceris MMX = indicated for UC
Less systemic absorption, potentially less SE
$$$
Immunosuppressives - Thiopurines
Aza (Azathioprine) & 6-MP (6-Mercaptopurine)
Aza converte to 6-MP by enzyme TPMT
caution in ppl who are not good metabolizers TPMT
AZA & 6-MP common SE
Anorexia
Nausea
Vomiting
Diarrhea
AZA & 6-MP Severe Adverse SE
Hematolig/Leukopenia = monitor WBC**
Hepatotoxicity = dose related, reversible
Pancreatitis
Hepatosplenic lymphoma
Drug interactions of AZA & 6-MP
Significant DI w/ Allopurinol, reduces 6-MP metabolism = inc lvls and toxicity
reconsider use or reduce AZA/6-MP dose by 25-30%
Onset of action AZA + 6-MP
2-3 months
> 4 months for optimal efficacy
Assessing TPMP phenotype prior to starting therapy….
pts who have low enzyme lvls increased risk of severe leukopenia
if no active TPMP activity, don’t initiate
if intermediate TPMP activity, reduce start dose 25-50%
Methotrexate info
- Limited role in UC, primarily used in CD
- Long term SE, monitor WBC, RBC,PLT
GI ulceration + bleed, hepatoxicity (ALT,ASLT, LFTs)
Pulmonary fibrosis/pneumonitis
Cyclosporine info
Primarily used in UC, typically not recommended for treatment of CD except for acute management of pts with severe fistulizng disease
used in hospital, have to monitor levels, bunch of DI CYP3A4
SE: HTN, edema, tremor, nephrotoxicity
Cyclosporine trough conc + response
300-500 mg/ml for IV
average response seen in 8 days
Immunosuppressives are usually used for….
maintenance remission therapy
due to long time to take to work
Infliximab common ADE
HA Abdominal pain Infections, URI, sinusitis Dyspnea Urticaria
fairly well tolerated overall
Inflixima info
black box warning for inc risk of developing infections
can reactivate latent TB
infusion reactions are possible, typically pts have fever, chills, and or pruritus
serum sickness with repeated doses are rare
Adalimumab (Humira) SE
fully homogenized, better tolerated
Common: HA, rash, antibody development, inject site reactions, URI, sinusitis
Less common: HTN, confusion, N/V/ab pain, serious infection
Golimumab Adverse side Effects
URI
Increased LFTs
Injection/dermatologic reactions
Golimumab (Simponi) Severe Side effects
Infections: Latent TB activation Hep B react Secondary malignancy CHF exacerbations MS (demylenating disease)
Certolizumab (Cimzia) info
Pegylated human anti-tnf
similar efficacy to humira + infliximab
SE:
inc site reaction, cytopenias, Hep B reactivation, new or worsening HF
Natalizumab (Tysabri) info
SE: rash, UTI, infection (flu), n, gastroenteritis, infusion related
Black box: increased risk of PML, often fatal
REMS restricted, access through TOUCH program
Vedolizumab (entyvio)
MOA: works on T cells
Common SE: HA, arterialgia, nasopharyngitis
Less common SE: Fatigue, skin rash, infection, UTI, increased LFTs
Ustekinumab (Stelara)
works on interleukins
SE: Serious infections, C.diff, UTI, some cases carcinoma
Tofacitinib (Xeljanz)
MOA: inhibit JAK1/3, oral drug
Txm adults with mod/sever active UC
SE: influenza, nasopharyngitis, modest LDL/HDL inc
Rare: serious infections
** FDA safety warning inc risk of VTE pts taking standard 10mg BID dose **
Upadacitinib (Rinvoq)
MOA: JAK1/3 inhib, also works on interleukin
SE ( >5%): URI, CK + LFT elevation, Acne, Neutropenia, Rash
Ozanimod (Zeposia)
MOA: block lymphocyte egress from lymph node, reduce inflammation response
Common SE: URI, LFT elevation, HA
Serious SE: Infections (viral/fungal), Bradyarrhythmias + condition delays, HTN< Respiratory decline, Macular edema
Biosimilars info
- similar amino acid sequences, but glycosylation differences between production can impact stability and immunogenicity
Must have same strength, dose form, route of admin and indication
Antibiotic usage
not used for much, very specific indications for a few such as Metronidazole and Ciprofloxacin
Mildly Active-Distal Ulcerative Colitis
Rectal (support + enema) mesalamine more effective than oral 5-ASA or topical steroids for distal disease
Combo oral + topical 5-ASAs more effective than either alone
Mesalamine prep typically better tolerated than sulfasalazine, usually 1st line***
Mildly Active-Distal Refractory UC
- Corticosteroids (PO or IV), Burst therapy, taper over 6-8wks…2-4wk if tolerated
- Budesonide MMX, alternative or addition to 5-ASA intolerant/non-responders
PO+rectal combo better than solo
AZA + 6-MP = limited role, poor risk/benefit, not recommended
Maintenance Remission w/ previously Mildly active Distal UC
- lower oral doses of agents (1g/day of 5-ASA)
- Oral+ topical formulations better than either alone
- Corticosteroids and budesonide not indicated
- Infliximab, AZA, 6-MP limited role, only in refractory pts
Mildy Active Extensive UC info
- Oral 5-ASA (2g/day) 1st line, recommend against alternative 5-ASA for pts who fail to achieve remission on initial 5-ASA, higher doses not associated with better remission
- oral steroids typically used pts dont respond to combo oral+rectal 5-ASAs
- Infliximab effective pts steroid refractory or dependent
Mildy Active Extensive UC 1st-3rd line
1st = oral Sulfasalazine or other 5-ASA 2-2.4g/day 2nd = Oral corticosteroids or budesonide as an alternative 3rd = Infliximab
Maintenance Remission pts w/ previously Mildy active Extensive UC
- Lower dose 5-ASA ( sulfasalazine, olsalazine, mesalamine, balsalazide)
- AZA or 6-MP maybe used
- TNFi (infliximab pref)
** chronic oral corticosteroids not indicated **
Mod-Severe Active Extensive UC, pts not req hospitalization
- Corticosteroid adjust can be considered
2. early biologic therapy recommended, anti TNF
Mod-Severe Active Extensive UC, pts not req hospitalization…Biologic Naive….
- infliximab
2. Vedolizumab
Mod-Severe Active Extensive UC, pts not req hospitalization….refractory to biologic agent….
Ustekinumab and tofacitinib
Mod-Severe Active Extensive UC, pts not req hospitalization combo therapy
Thiopurines or MTX + biologic is better than biologic monotherapy
Severe UC req Hospitalization or Fulminant Extensive disease
- give steroid
1a. no response = cyclosporine or infliximab - if remission continue therapy, if no remission Colectomy
1b. if remission = change to prednisone, add AZA/6-MP/infliximab or adalimumab and attempt withdrawal of steroid, continue if remission achieved
Mild-Moderate Active CD
Systemic corticosteroids = prednisone w/ taper effective inducing remission
Antibiotics - limited efficacy, insufficient data
Controversial 1st line = Sulfasalazine (when involves colon) + Mesalamine ( targeting ill disease, better tolerated)
Viable 1st line for CD confined to ileum and/or right colon?
Controlled release budesonide (Entocort)
Moderate-severe active CD
Taper oral corticosteroids
anti-TNF used, combo more effective than mono
Ustekinumab = treatment resistant pts
AZA, 6-MP, Max = not effective short term
Cyclosporine, mycophenolate, taco = controversial but generally not efficacious
Severe/fulminant Active Disease CD
- rule out obstruction, mass, abscess
- IV corticosteroids 1st line
- Limited data supporting anti-TNFs
Perianal + Fistulizing disease
Anti-TNFs
AZA, 6-MP
Antibiotics
Maintenance therapy for CD
long term corticosteroids not recommended
AZA, 6-MP preferred over MTX
5-ASA not effective/recommended
