IBD Flashcards
IBD definition
mucosal inflammatory conditions with chronic or recurring immune response and inflammation of the gastrointestinal (GI) tract
two types of IBD
Ulcerative Colitis (UC): mucosal inflammation confined to rectum and colon Crohn’s Disease (CD): transmural inflammation of GI tract that can affect any part from the mouth to the anus
epidemiology of IBD
most prevalent in western countries
both sexes affected equally
peak incidence in second (CD) or third decade (UC)
etiology of IBD
combination of immunologic, infectious, genetic, environmental factors - immune dysregulation, microflora of GI tract may trigger
immunologic etiology of IBD
both autoimmune and non-autoimmune mechanisms
innate immune system involves intestinal barrier function, is associated with secretions in response to stimuli
gut wall infiltrated by WBCs - granuloma formation
cytokine disregulation
microbial etiology of IBD
luminal microorganisms thought to be important in initiation of inflammation however no definitive infectious etiology
-shift toward more proinflammatory bacteria
-increased density of microflora
-potential loss of tolerance to normal GI flora
-bacterial antigens/ligands may induce and
propagate inflammation
-“microbiome” - ecological community of commensal, symbiotic, and pathogenic microorganisms
genetic etiology in IBD
high concordance rate in monozygotic twins
first degree relatives have 20x risk of IBD
not a single gene phenomenon
psychological etiology in IBD
stess may correlate with disease flares and impact QOL
environmental etiology in IBD
“hygiene hypothesis”: cleaner conditions in developed countries expose patients to fewer pathogens/antigens at a young age - potentially altered immune response when encountered later in life
diet (potential association - causality unclear)
smoking - potentially protective in UC (reduced disease activity, fewer flares); associated with an increase frequency and severity of CD
Drug related etiology of IBD
NSAIDs - may trigger disease occurrence or lead to flares, unclear whether COX-2 selective agents are associated with a decreased risk, generally avoid NSAIDs in pts with IBD
antibiotics - potential association, however causal relationship unclear
UC pathophysiology
confined to rectum and colon and affects mucosal and submucosal layers (more superficial than CD)
-abscess formation in mucosal crypts, coalescence results in ulceration
extension and coalescence of ulcers may surround areas of normal tissue
mucosal damage and friability can result in substantial diarrhea and bleeding
complications of UC
local, systemic and extraintestinal complications
local - hemorrhoids, anal fissures, perirectal abcesses
other major complications: colonic perforation (can be w/wo toxic megacolon), massive colonic hemorrhage, colonic stricture
toxic megacolon
complication of UC - severe and potentially fatal
segmental or total colonic distention with acute colitis and signs of systemic toxicity
increase depth of ulceration
vasculitis and thrombosis
colonic dilation and potential perforation
associated with fever, tachycardia, abdominal distention, elevated WBCs
colonic dysplasia/colorectal cancer (CRC)
risk of colonic dysplasia w transition to CRC is 5x greater in UC
cumulative risk of CRC is up to 20-30% at 30 years
screening colonoscopy with biopsies recommended at 8 years after UC onset and every 1-2 years after that
CD pathophysiology
transmural inflammation
anywhere in GI tract (terminal ileum most common)
often discontinuous (normal bowel separating diseased bowel)
deep, elongated ulcers, cobblestone appearance
bowel wall injury may be extensive, associated with luminal narrowing
complications of CD
small bowel stricture and obstruction possible
fistula common (20-40% lifetime risk) - fistula = pathologic connection between bowel and another tissue (skin, another segment of GI tract, bladder, or vagina)
less bleeding than UC (although anemia possible)
risk of carcinoma is increased, but not to the extent of UC
nutritional deficiencies common - weight loss, growth failure in children, iron deficiency anemia, vit B12 def., folate def., hypoalbuminemia, hypokalemia, osteomalacia
extraintestinal manifestations of IBD
hepatobiliary - common (5-95% incidence) - hepatic: fatty liver, pericholangitis, autoimmune hepatits, cirrhosis; biliary - primary sclerosing cholangitis (PSC), cholangiocarcinoma, cholelithiasis
occular - iritis, uveitis, episcleritis, conjuctivits
bone and joint - arthritis: asymmetrical, migratory, typically involes one/few large joints and parallels disease activity; may be at increase risk for metabolic bone disease and osteoporosis (nutrient definiciences, inflammation, hypogonadism, use of CSs)
hematologic - anemia
coagulation - increase risk of VTE; higher during flares, consider prophylaxis if admitted for flare
dermatologic and mucocutaneous - variety of skin and mucosal lesions
clinical presentation of UC
highly variable; may include intermittent illness and periods of remission diagnosis made on clinical suspicion and confirmed by endoscopy (colonoscopy or sigmoidoscopy) and biopsy disease extent (location of inflammation) determined by endoscopy
signs and symptoms of UC
abdominal cramping
frequent BMs +/- blood +/- mucous (can range from frequent small volume to profuse diarrhea)
weight loss
paradoxical constipation possible
fever/tachycardia (esp. in severe disease)
extraintestinal: blurred vision/ocular signs; arthritis; dermatologic manifestations
physical examination of UC
hemorrhoids, anal fissures, perirectal abscesses may be present
dermatologic/ocular findings
lab tests for UC
decreased Hb/HCT
increased ESR/CRP
leukocytosis, hypoalbuminemia (severe dz)
(+) perinuclear antineutrophil cytoplasmicantibodies
fecal calprotectin and fecal lactoferrin
types of UC
distal (left-sided): distal to splenic flexure
extensive: extending proximal to splenic flexure
proctitis: involving the rectal area
proctosigmoiditis: involving rectum and sigmoid colon
pancolitis: involving majority of colon
UC disease classification
determined by s/sxs
- Mild: under 4 stools/day (+/- blood); no systemic disturbance; normal ESR
- Moderate: over 4 stools/day; minimal systemic disturbance
- Severe: over 6 stools/day with blood; evidence of systemic disturbance (fever, tachycardia, anemia, or ESR over 30 mm/h)
- Fulminant: over 10 stools/day with continuous bleeding; toxicity (severe systemic disturbances); abdominal tenderness; need for transfusion; colonic dilation
clinical presentation of CD
highly variable, characterized by periods of remission and exacerbation
typical presentation includes diarrhea and abdominal pain - hematochezia in around 50% (less if no colonic involvement), should suspect diagnosis in children with impaired growth, esp. if associated w abdominal pain
diagnosis involves clinical evaluation in addition to endoscopic (upper and lower), laboratory, radiologic testing
s/sxs of CD
malaise, fever abdominal pain frequent BMs hematochezia fistula weight loss/malnutrition arthritis
PE of CD
abdominal mass/tenderness
perianal fissure, fistula
laboratory tests with CD
Hb/HCT
increased WBCs, ESR, CRP
(+) anti-Saccharomyces cervisiae antibodies
fecal calprotectin and fecal lactoferrin
CD disease classification
no global classification system
CDAI (crohn’s disease activity index) - used to gauge response to therapy and determine remission
treatment guidelines often use “clinical picture”
mild-moderate: ambulatory with minimal other symptoms (dehydration, systemic toxicity, loss of body weight, abdominal tenderness), no obstruction
moderate-severe: patients who fail therapy for mild-moderate
disease, or those with fever, weight loss, abdominal pain/tenderness, vomiting, obstruction, anemia
severe-fulminant: persistent symptoms or evidence of systemic toxicity despite corticosteroid or biologic treatment, or presence of cachexia, rebound tenderness, intestinal obstruction, or abscess
IBD treatment overview
pharmacologic therapy, surgical therapy, nutrition support, treatment of complications, avoiding drugs that may exacerbate IBD
goals of therapy: highly individualized; may include:
-resolve acute inflammation/treatment of disease flare
*resolve and/or prevent complications
-maintain remission
*alleviate extraintestinal manifestations
-avoid need for surgical palliation/cure (patient priority)
-surgical palliation/cure
-maintain QOL
inducing and maintaining remission** is an important ascept of therapy to improve outcomes and QOL and reduce complications - mucosal healing may be associated with better long term outcomes
nonpharm therapy for IBD
nutrition support - no specific diet shown to be beneficial, address nutritional deficiencies, impaired absorption (enteral supplementation if necessary, parenteral nutrition - avoid unless absolutely necessary, supplement vitamin/mineral deficiencies), probiotic therapy
surgery - resecting areas of inflammation, rates in UC may be around 5-30%, indications for surgery in CD are less established
overview of pharm therapy in IBD
integral role, however no agents are curative
ASAs (aminosalicylates) - sulfasalazine, mesalamine (5-ASA)
corticosteroids (local and systemic)
immunomodulators (immunosuppressives) - azathioprine, mercaptopurine (MP), cyclosporine, methotrexate
biologics - anti-TNF-α agents (infliximab, adalimumab, certolizumab, golimumab); inhibitors of leukocyte adhesion/migration (natalizumab, vedolizumab)
antimicrobials (metronidazole, ciprofloxacin)
sulfasalazine
sulfapyridine (a sulfonamide) + 5-ASA (mesalamine)
- cleaved by colonic bacteria to release sulfapyridine (absorbed and renally excreted) and 5-ASA (mainly remains in lumen, excreted in stool)
- sulfapyridine is inactive, but associated with ADRs
- 5-ASA is the active component, exerts actions locally - MOA may include anti-inflammatory effects, free radical scavenging
mesalamine
can administer mesalamine alone
-rapidly and completely absorbed in small intestine but not colon
-formulation is important to deliver to affected area
-topical (enemas): left-sided disease
-suppository: proctitis
-oral - delayed/controlled release
generally topical is more effective than oral
can use oral and topical together
apriso
oral mesalamine agent
0.375 g in ER/DR capsule - dissolves at pH 6+
releases in colon*
dosed once daily*
lialda
oral mesalamine agent
1.2 g in ER/DR capsule - film dissolves at pH 6.8+
drug releases evenly throughout colon*
dosed once daily*
pentasa
oral mesalamine agent
250 mg or 500 mg in CR capsules
releases in duodenum and ileum - up to 60% of dose reaches colon*
dosed QID*
asacol HD and delzicol
oral mesalamine agents
800 mg (asacol HD) or 400 mg (delzicol) in pH dependent coating - dissolves at pH 7+
releases in terminal ilium*
dosed TID*
olsalazine
dipentum oral mesalamine agent 250 mg dimer of 2 5-ASA molecules - mesalamine released after colonic bacteria cleaves bond release in colon dosed BID
balsalazide
colazal oral mesalamine agent prodrug - released after colonic bacteria cleaves bond release in colon 750 mg tab dosed TID
sulfasalazine ADRs
over 10% - NV, HA, anorexia, rash - initiate low dose, increase slowly over 1-2 weeks
under 10%: anemia, hepatotoxicity, thrombocytopenia
may be assocaited with hypersensitivity rxns in sulfa allergy
monitpr CBC and LFTs at baseline, every other week for first 3 months, monthly for second 3 months, and periodically therafter, monitor BUN/SCr periodically
drug interactions: antiplatelet/anticoagulant/NSAID - increased bleeding risk
mesalamine ADRs
better tolerated than sulfasalazine
common: NV, HA
olsalazine: diarrhea
less common: diarrhea, rash, constipation, anemia, abnormal LFTs, UC exacerbation
drug interactions: antiplate/anticoag/NSAID - increased bleeding risk, agents affecting gastric pH - could influence release of drug in pH dependent dosage forms
corticosteroids used in IBD
MOA: anti-inflammatory (note, unclear whether primary effect systemic or local)
can be used parenterally (severe exacerbation/complication), orally, or rectally
use for induction of remission, but not for maintenance
Rectal Hydrocortisone (generally around 100-200 mg per day):
-suppositories (Proctocort, Hemril), foam (Cortifoam), enema (Cortenema, Colocort)
-note that systemic absorption is possible with rectal formulations
budesonide in IBD
administered PO in CR formulation
extensive first pass metabolism - minimal systemic exposure (9-21%)
6-8 mg/day for up to 8 weeks (possibly 16 wks)
Enterocort EC: dosage form dissolves at pH > 5.5 (ileum), also available as enema
Uceris: dosage covering dissolves at pH ≥ 7 (colon), polymer film provides extended release
budesonide ADRs
possible similar to other glucocorticoids, however generally very well tolerated
interactions: CYP3A inhibitors (ketoconazole, grapefruit juice, many others) - may increase systemic exposure by loss of high first pass
systemic CSs in IBD
goal: remission and off steroid
oral prednisone or prednisolone
-40-60 mg/day
-taper 5-10 mg/week until a dose of 20 mg/day is reached, then taper 2.5 mg/week
intravenous methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h)
may be used for disease flares/induction of remission
systemic CSs ADRs
-give calcium (1000-1500 mg/day) and vitamin D (800 U/day) while on steroids
-may consider bisphosphonate tx in patients w risks for osteoporosis, pts using for > 3 months, recurrent users
monitoring: see previous notes on corticosteroids
-consider occasional bone mineral density scan (DEXA) in
pts over 60, pts w risks for osteoporosis, pts using for over 3 months, recurrent users
azathioprine (AZA) and mercaptopurine (MP, 6-MP)
can be effective in long term txt of UC and CD
-generally reserved for pts who fail 5-ASA tx, and/or pts who are refractory to/dependent on steroids: can induce and maintain remission, steroid sparing, can use in conjunction w other drugs (5-ASAs, steroids, TNF-α antagonists), generally need to be used for extended periods* (weeks-months) before benefits observed
AZA is a prodrug that is rapidly converted to 6-MP
AZA: 0.5-1.5 mg/kg IBW, increase to a max of 2.5 mg/kg/d
MP: 0.25-0.5 mg/kg IBW, increase to a max of 1.0- 1.5 mg/kg/d
AZA and 6-MP ADRs and monitoring
GI: N/V/D, anorexia, stomatitis
hematologic: bone marrow suppression (need TMPT genotype before initiation)
hepatic: hepatotoxicity
idiosyncratic: fever, rash, arthralgia, pancreatitis
monitoring:
baseline TPMT*
CBC baseline and q week for 1st month, q 1-2 weeks after a dose change, q 1-3 months thereafter
LFTs baseline and q 2 weeks until stable, then periodically
cyclosporine in IBD
can be effective inducing remission in patients with
refractory IBD (better data for UC)
-not an option for long term use (i.e., use as “bridge therapy”)
-generally reserved for pts who are refractory to/dependent on steroids: may delay colectomy, not for patients who have failed AZA or 6-MP, unclear whether it can be used following biologics
-initial continuous IV infusion 2-4 mg/kg/day
-PO conversion: double the IV dose, administered in divided doses q12h - taper over several weeks if response (up to several months)
cyclosporine ADRs and monitoring
nephrotoxicity (does related)
neurotoxicity
metabolic (HTN, hyperlipidemia, hyperglycemia)
other: GI upset, gingival hyperplasia, hirsutism
monitor:
BP baseline and q visit
BUN/SCr baseline and q 2 weeks until stable, then periodically
LFTs baseline q 2 weeks until stable, then periodically
cya tr. conc goal ~200-400 ng/ml (t1/2 up to 24 h)
cyclosporine drug interactions
substrate for CYP3A and P-glycoprotein
- drugs/foods that can increase cyclosporine concentrations (not inclusive list): azole anti-fungals, macrolide antibiotics, calcium channel blockers, grapefruit and grapefruit juice
- drugs that can decrease cyclosporine concentrations (not inclusive list): phenytoin, rifampin
methotrexate
can be useful for treatment and maintenance of CD - may have steroid sparing effects, assist in inducing remission, allow steroid-tapering
role in UC less defined
15-25 mg SC/IM q week
methotrexate ADRs and monitoring
hematologic: bone marrow suppression (add folic acid 1 mg/day) GI: N/V/D, stomatitis, mucositis hepatic: cirrhosis, hepatitis, fibrosis (concern after 1.5 g in lifetime) pulm: hypersensitivity pneumonitis derm: rash, urticaria, alopecia teratogenic (contraception) monitoring: CXR baseline CBC baseline and q4-8 weeks SCr baseline and q4-8 weeks LFTs baseline and q4-8 weeks
methotrexate contraindications
pregnancy pleural effusions chronic liver disease/EtOH abuse immunodeficiency preexisting blood dyscrasias leukopenia/t.cytopenia ClCr under 40 ml/min
biologics overview
infliximab (Remicade) -anti-TNF- α antibody -CD and UC adalimumab (Humira) -anti-TNF- α antibody -CD and UC golimumab (Simponi) -human monoclonal antiTNF- α antibody -UC certolizumab pegol (Cimzia) -human pegylaged antiTNF- α Fab fragment -CD natalizumab (Tysabri) -anti-α-subunit of integrin's (prevents leukocyte adhesion/migration) -CD vedolizumab (Entyvio) -anti-α4β7 integrin antibody (α4β7 integrin is expressed on subset of T-lymphocytes) -UC and CD
TNFa inhibitors ADRs
risk of serious infections (bacterial, viral, fungal)
**avoid if active infection
**tuberculin test (“PPD”), CXR, Hepatitis B/C prior to therapy
-ensure vaccinations up to date
**live vaccines contraindicated during tx and for 3 mo after
injection site reactions - esp. with SC injection
risk of malignancy (lymphoma)
hepatosplenic T-cell lymphoma (HSTCL) risk (when combined with AZA)
risk of demyelinating disease
0C/O in pts w history of cancer, demyelinating CNS disease, optic neuritis
may exacerbate CHF (c/o in NYHA class III/IV)
monitoring TNFa inhibitors
CXR, PPD at baseline
S/S of infection (and patient self S/S of infection report)
UA at baseline and q4-12 weeks
CBC at baseline and q4-12 weeks
SCr, lytes at baseline and q4-12 weeks
LFTs at baseline and q4-12 weeks (possibly more frequent)
Hep B, C inflammatory markers (e.g., Creactive
protein)
infliximab
UC and CD
-mod - severe active CD and UC, steroid-dependent or fistulizing disease
-induction and maintenance therapy
IV infusion (2 hours*): 5 mg/kg at 0, 2 and 6 weeks, then 5-10 mg/kg q 8 weeks
development of antibodies to infliximab (a.k.a., ATIs, ADAs)
-decrease treatment response, potentially increase chance of infection
-up to 10% of pts/year need to d/c infliximab
-can escalate dose, decrease dosing interval
-TDM (drug and antibodies) may be of value
combining with immunosuppressives (e.g., azathioprine) may be of value** (and may risks of ADRs)
hepatosplenic T-cell lymphoma (HSTCL) risk - increased if co-administered w azathioprine
infusion-related reactions - acute or delayed
additional monitoring: s/s of infection, vitals (each dose), infusion reactions (each dose), TDM (consider if treatment failure)
adalimumab
UC and CD
-mod - severe active CD and UC, steroid-dependent
-can use for pts with poor response to infliximab
-induction and maintenance therapy
SQ injection: 160 mg at wk. 0, 80 mg at wk. 2, then 40 mg every second wk.
-self-administration technique important**
-in non-response/loss of response can increase dose to 80 mg q other wk. or 40 mg q wk.
development of ADAs
-human derived* (potentially less likely than infliximab)
-measurement of antibodies possible
golimumab
UC
-mod - severe active UC, steroid-dependent
-induction and maintenance therapy
SQ injection: 200 mg at wk. 0, 100 mg at wk. 2, then 100 mg every 4 wks
-self-administration technique important
-no guidelines for dose escalation
development of ADAs
-human derived (potentially less likely than infliximab)
certolizumab
CD
-mod - severe active CD, steroid-dependent
-induction and maintenance therapy
SQ injection: 400 mg at wk. 0, 2, and 4, then 400 mg every 4 wks
-self-administration technique important
-no guidelines for dose escalation
development of ADAs
natalizumab
anti-α-subunit of integrin’s (prevents leukocyte adhesion/migration)
CD
-inducing and maintaining remission
-can use in pts who fail/don’t tolerate TNF-α inhibitors
-NOT to be used in combination w immunosuppressant’s,
TNF-α inhibitors
300 mg IV q 4 wks
-1 hour infusion
-**d/c in patients w no benefit by 12 weeks and/or who are still steroid dependent within 6 months
associated with progressive multifocal leukoencephalopathy (PML)
-rare, lethal/disabling, untreatable CNS disorder related to opportunistic viral infection (JC virus)
-available only through restricted distribution program
-able to test for JC antibody
-increased risk with: longer duration of therapy (over 2 years), prior immunosuppressant use, JC antibody positive
-monitor closely for neurological events
other ADRs similar to other biologics - can see hypersensitivity reactions, ADAs
vedolizumab
anti-α4β7 integrin antibody (α4β7 integrin is expressed on subset of T-lymphocytes)
UC and CD - inducing and maintaining remission, decreasing steroid dependence
300 mg IV at 0, 2, and 6 wks, then q 8 wks thereafter (infused over 30 min)
ADRs similar to other biologics
-can see hypersensitivity reactions, ADAs
-PML not observed however close monitoring
warranted due to similar MOA of natalizumab
therapeutic drug monitoring (TDB) of biologics
loss of response -
subtherapeutic level with no/low ADA - increase dose or decrease interval; consider adding immunomodulator
therapeutic level - switch to vedolizumab with or without immunomodulator
subtherapeutic level with high ADA - switch within class
antimicrobials used in IBD
ciprofloxacin, metronidazole
-can be used as adjunctive therapy in CD (and UC)
in combination - may be of value in inducing remission
-may be used in CD associated with fistulas/abscesses, perianal involvement
rifamycin antibiotics also used
ADRs:
-agent specific ADRs
-resistance
-Clostridium difficile
mild-moderate active UC
left-sided disease - within reach of enemas
proctitis - within reach of suppositories
extensive disease, pancolitis - requires systemic tx
oral and/or topical ASAs for mild-mod active UC
oral and/or topical ASAs
-if extensive disease - oral sulfasalazine or oral mesalamine derivative
-if distal disease, topical mesalamine (enema or suppository) may be preferred
-combo of oral and topical may be more effective for pts with left-sided/extensive disease
if oral tx:
-mesalamine derivatives better tolerated than sulfasalazine
-sulfasalazine: 4-6 g/day in divided doses
-mesalamine derivatives: 2.4-4.8 g/day
-consider compliance, convenience, financial resources in product choice
treatment for mild-mod active AC outside of ASAa
CR budesonide is alternative
PO corticosteroids (prednisone 40-60 mg/day) may be used for patients refractory to ASAs
AZA or 6-MP may be used for patients refractory to ASAs
topical corticosteroids (foams, enemas, suppository) are effective for distal disease (ie, left sided, proctitis)
moderate-severe active UC
systemic corticosteroids (PO prednisone 40-60 mg/day)
consider TNF-α inhibitors in pts unresponsive to ASAs/other therapy, pts who are steroid dependent, pts who fail steroids
infliximab + AZA may be superior to monotherapy
severe-fulminant UC
require inpatient tx
consider NPO (bowel rest)
parenteral corticosteroids
-methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h)
-generally treat 3-7 days (then transition to PO)
consider TNF-α inhibitors or cyclosporine in pts
unresponsive to IV steroids
-cyclosporine: start IV, transition to PO, with transition to 6-MP or AZA - effective, but may delay rather than prevent colectomy
infliximab - similar efficacy to cyclosporine
UC: maintenance of remission
generally use an ASA, a TNF-α antagonist (infliximab and adalimumab), azathioprine, or 6-MP
choice depends on part in the tx required to induce remission
no role for corticosteroids
ASAs
-newer mesalamine derivatives better tolerated than sulfasalazine (2-2.4 g/day mesalamine equiv)
-may use mesalamine enemas (if left-sided disease) or suppositories (if proctitis)
-may use combination of topical/systemic (more effective than either alone)
in pts who are steroid dependent or unresponsive to ASAs
-azathioprine or 6-MP (slow to work: 3-6 months) - also consider as maintenance for pts who are transitioned to oral cyclosporine for induction of remission
-TNF-α antagonist for pts who fail azathioprine or pts who required a TNF-α antagonist for induction of remission
consider probiotic therapy
mild-moderate active CD
sulfasalazine, newer mesalamine derivatives have minimal efficacy**, no longer recommended by some experts (controversial)
-despite this, mesalamine derivatives frequently tried since well tolerated/familiar
-consider formulation and site of action (e.g., Pentasa releases in small intestine)
controlled release budesonide*
-option for pts with ileal (distal) or right-sided disease
antibiotics
-e.g. metronidazole +/- ciprofloxacin
-variable efficacy, possible option if perianal disease, unresponsive to sulfasalazine, generally not first line
moderate-severe active CD
systemic corticosteroids (PO prednisone 40-60 mg/day)
-tx until resolution of sx and resumption of wt gain
hospitalized patients may receive IV corticosteroids
-methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h)
immunomodulators (AZA and 6-MP) are not recommended to induce remission** (may help maintain remission after induced w steroids)
-generally reserved for pts who are not responding to standard tx or who are steroid dependent
MTX is alternative to AZA
-induction and/or maintenance in steroid dependent/refractory
TNF-α antagonists also effective
-can use in patients failing immunosuppressive tx, steroid dependent pts
-infliximab + AZA may be more effective than either alone
adalimumab may be used - SC administration, possible option in pts who lose response to infliximab, others: certolizumab, natalizumab, vedolizumab
severe-fulminant CD
require inpatient tx**
consider NPO (bowel rest)
parenteral corticosteroids (if no abscess)
-methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h)
-generally treat 3-7 days (then transition to PO)
consider cyclosporine (or tacrolimus) in pts unresponsive to IV steroids
-limited data, start IV, transition to PO
may consider infliximab (or other biologic) if not attempted prior
CD maintenance of remission
minimal evidence sulfasalazine and PO mesalamine derivatives are effective
-may try due to favorable adverse effect profile - mesalamine may have a role in preventing post-surgical relapse
no role for systemic corticosteroids
budesonide has minimal long-term efficacy
limited data regarding antibiotics
AZA and 6-MP are effective
-esp. in steroid-induced or infliximab-induced remission
-often consider first line
MTX
-alternative to AZA and 6-MP, esp. in pts w initial response to MTX
TNF-α antagonists are options for CD maintenance
-infliximab may be used with AZA or 6-MP
-others: natalizumab, vedolizumab
-clinical controversy: bottom-up or top-down approach
