Treatment of UC

Drug and dosing guidelines based on disease severity and location are presented in Table 19-4.

Mild to Moderate Active UC

Treatment of acute episodes of UC is dictated by the severity and extent of disease, and first-line therapy of mild to moderate disease involves oral or topical aminosalicylate derivatives. Topical suppositories and enemas are preferred for active distal UC (left-sided disease and proctitis), as they deliver mesalamine directly to the site of inflammation. Topical mesalamine is superior to both topical corticosteroids and oral aminosalicylates for inducing remission in active mild to moderate UC.1,31-34 Enemas are appropriate for patients with left-sided disease, as the medication will reach the splenic flexure. Suppositories deliver mesalamine up to approximately 20 cm and are most appropriate for treating proctitis.6,7,31

Topical mesalamine products provide a more rapid response than oral preparations. Improvement in symptoms may be seen in as little as 2 days, but up to 4 weeks of treatment may be necessary for maximal response. Oral and topical mesalamine preparations maybe used together to provide maximal effect. Oral mesalamine may also be used for patients who are unwilling to use topical preparations.31,34

Topical corticosteroids are typically reserved for patients who do not respond to topical mesalamine.1,23 Patients should be properly educated regarding appropriate use of topical products. This includes proper administration and adequate retention of topical mesalamine products in order to maximize efficacy.

Table 19-4 Treatment Recommendations for UC

Discair Scvurily and Location

Active Disease

Maintenance of Remission

Mild Disfiist

PlJOCTltls

Ltf 1 WfctJ <Jistinc

CcHiths

Modi rate Dili a»

flUKIltii liil-AJeddfetJiv:

toiler

Siwt of F«lri|ntnl Disease

^«alamlne :uppmlrofy 1 g wtfly rtJ'ly

Mttakunlnc mrm I g iCCUlly dally, or

MiWUiinlne 2A-4& ■q/OJ* Of sulfasalazine i-f> Lirttev □rally

Mesjldnine 2A - 4JS g/tijy or juHasaldiinr <1 • 6 gftjdif Ofjiy

MtJMUiiilrteSuWXKiKiiy T Q Wilflv daily;

li no response lomeialiJnlrw.

MC4al>nir*!prii:iM I g «xljlly Jl tMXJtimO Ot MeHUrrme 2.4-AH riAHy tx iLlfAiilwne ■1-6 gAJay «ally

Miy-COfritiiW-cricmj iirti Oil (NCraeies

Mcialdnine - g/djy or sulfasaidiine 4-6 gftJay erjiy;

• Pwdnfcoric 40-60 mgMay dally; or

Hlrtlr-mcljwfn; 300 rug [V daily ((jf t\juivaliiH) * 7 rtayiof

If ns rftpenit ir> IV tiy lieeiwsiih c< ill liKiirtjIt

• Cyclosporin? 4 mg/kgfdiy IV

h^v reduce snifiposltioNv frequency® I g 3 limes/iwek May nLtlud.' LfttmJ frciquonty CO I g uvCry OLhci <ity. or Taper (oin«ali<Tiine ij-Mcjy^or sniifiWiazii*? 2—5 q.'tlav irf all V Tdpcr to mcvjljminc 1.6 2.4 gi/Ud/or iijltiiviliiinc 2—4 out/

M^y reduce iuppoiittiiy fne<iuencyii> i g l limei^week:

tape* prednisone as soon as posubtf", Cofiiiki JdJnig wdthk))3"in£ c f -WP li-lS mtf/hjAJjy Of ally

MJy rtduuL-CiiCmJlrcquCTity CO I g 3 linnciMcck if fiymjHtims pemWi; Mjy nedute dost of oral agenrts-i lymploms permil; OSnudir JiMiny JJJlhiOuiint Or 6-MP 1.5-2.5- ing/kg/ itiyofaly

Taper rncsaflamint.' to Ih-iA t^Uaya vjlftoahiinc 2-1 (>tJjy CJJflly; If prednisones Infliximab we«e re^uNed1

• Taper p<pdnbone as soon as possible;

• Give infliximab 5- mg/kg IV every 8 weetl Coftifciei adifm? «athlnpine Of & IS-15 iruykt)/diy orally

Change W Oral torlkoatopd and taper« soon as pOSSMc

Rntarl oral metalarnlne or sulfasalazine Mj* (OfiintlC iriil:! njli .n inslnt<.+ijr)te dews ci t mg/kg every d weeks

For patients with more extensive disease extending proximal to the splenic flexure, oral sulfasalazine or any of the newer oral mesalamine products is considered firstline therapy.1 Doses should provide 4 to 6 g of sulfasalazine or 4.8 g of mesalamine. While little differences in efficacy exist between mesalamine products, sulfasalazine and olsalazine have a higher incidence of adverse effects.18 Use of the once-daily for-

mulations of mesalamine may improve patient adherence.18'34 Induction of remission may require 4 to 8 weeks of therapy at appropriate treatment doses.

Oral corticosteroids may be used for patients who are unresponsive to sulfasalazine or mesalamine. Prednisone doses of 40 to 60 mg/day (or equivalent) are recommended.1'23 Azathioprine or 6-MP is used for patients unresponsive to corticosteroids or those who become steroid dependent. Infliximab 5 mg/kg may also be used for patients who are unresponsive to conventional oral therapies and may reduce the need for colectomy after 3 months of treatment. Infliximab may also be used in patients who are refractory to or dependent on corticosteroids.35'36

Severe or Fulminant UC

Patients with severe UC symptoms require hospitalization for management of their disease. If the patient is unresponsive to oral or topical mesalamine and oral corticosteroids, then a course of IV corticosteroids should be initiated.1 Hydrocortisone 300

mg/day given in three divided doses or methylprednisolone 60 mg daily for 7 to 10

days are the preferred therapies.

Infliximab 5 mg/kg is also an option for severe UC. Cyclosporine 2 to 4 mg/kg/day given as a continuous IV infusion should be reserved for patients unresponsive to 7 to 10 days of IV corticosteroid therapy.

Patients with fulminant disease are treated similarly, although infliximab is not indicated for this population. Patients with fulminant UC should be assessed for signs of significant systemic toxicity or colonic dilation, which may require earlier surgical intervention.

Maintenance of Remission

Unfortunately, up to 50% of patients receiving oral therapies and up to 70% of untreated patients relapse within 1 year after achieving remission.26 For this reason, patients may require maintenance drug therapy indefinitely to preserve remission.

® Maintenance of remission of UC may be achieved with oral or topical aminosalicylates. In patients with proctitis, mesalamine suppositories 1 g daily may prevent relapse in up to 90% of patients.1,7,31 Mesalamine enemas are appropriate for left-sided disease and may often be dosed two to three times weekly. Oral mesalamine at lower doses (e.g., 1.2 to 1.6 g/day) maybe combined with topical therapies to maintain remission. Topical or oral corticosteroids are not effective for maintaining remission of distal UC and should be avoided.

Oral sulfasalazine or mesalamine is effective in maintaining remission in patients with more extensive disease.1,26 Lower daily doses (e.g., 2 to 4 g sulfasalazine or 1.6 to 2.4 g mesalamine) may be used for disease maintenance. As with distal UC, oral corticosteroids are not effective for maintaining remission and should be avoided due to the high incidence of adverse effects.

® Immunosuppressants such as azathioprine or 6-MP can be used for unresponsive patients or those who develop corticosteroid dependency. Remission may be maintained in up to 58% of patients after 5 years of treatment.1,25 Intermittent infliximab dosing (5 mg/kg IV every 8 weeks) may be used to maintain disease remission and reduce the need for corticosteroids in patients with moderate to severe UC. Colectomy is an option for patients with progressive disease who cannot be maintained on drug therapy alone.

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