The Management of Steroid Dependency in Ulcerative Colitis

Summary and Introduction

Summary

Background: Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy.
Aim: To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis.
Results: The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated.
Conclusions: Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.

Introduction

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) characterized by a chronic relapsing/intermittent clinical course.^[1,2] Its prognosis has changed over the decades since the first descriptions of significant mortality 50 years ago.^[3] The introduction of safe and effective therapies and better surgical procedures has improved the clinical course of the disease. Despite these recent successes, a significant proportion of patients continues to suffer from particularly resistant forms of disease leading to the need for repeated therapies with significant toxicity and even colectomy, which is potentially curative but often unacceptable in the patient's eyes.

Systemic corticosteroids (CS) have been used to treat patients with active IBD for over 50 years. In 1955, Truelove and Witts showed that oral cortisone effectively induced remission in patients with active UC.^[4] CS are rapidly active and highly effective, making them the drug of choice for the initial management of moderate to severe active UC.^[5,6] Nevertheless, steroid-treated active patients may show different patterns of response to this therapy. One group will have good results, achieving symptom-free periods of satisfactory length; another group will respond well initially but lose benefit as the treatment is tapered or stopped. A third group will show complete refractoriness to the drugs despite high doses or prolonged therapies, experiencing only their side effects and finally needing colectomy.

The purpose of this report was to describe the available data about the management of the specific subset of steroid-dependent UC patients, in whom clinicians can again obtain some good response with systemic CS (unlike steroid refractory patients), but the relapse will occur, as the dose is decreased or a few weeks or months after discontinuation, making it necessary to increase the dosage again or resume treatment to achieve short-term control of symptoms. No specific reviews are currently available directly addressing this topic.^[7,8] In this paper, we gave prominence to controlled studies, stressing the need to consider only evidence-based results from studies that specifically described this particular subset of patients, in order not to generalize data referring to steroid refractoriness, rather than dependency. To be considered effective in this clinical scenario, a drug should be able to establish remission, prevent relapse and limit exposure to CS.

Cite this: The Management of Steroid Dependency in Ulcerative Colitis - Medscape - Mar 09, 2008.

Table 2. Trials With Methotrexate in Ulcerative Colitis (See Text)
Reference	Design	No. of patients	Target population	Treatment duration	Route	Results
Kozarek (1989)^[53]	Open	7	UC refractory to steroids/ salycilates/metronidazole	12 weeks	25 mg/wk IM	Significant activity index reduction in 5/7 patients Prednisone dose significantly reduced No endoscopic healing
Baron (1993)⁵⁴	Open	8	Steroid-dependent andrefractory UC	12weeks	15 mg/wk OS	Prednisone dose significantly reduced No complete remission Partial response in 3/8 patients
Oren (1996)⁵⁶	Placebo controlled	67	Steroid-dependent UC	9 months	12,5 mg/wk OS	No differences with placebo in indcluding remission (46.7% vs. 48.6%) and in relapse rate after first remission (44.4% vs. 64.3%)
Matè-Jimenez (2000)^[48]	MP/5 controlled	34	Steroid-dependent UC, AZA refractory or intolerant	30–76 weeks	15 mg/wk OS	Remission AZA = 79% vs MTX = 58% vs. ASA = 25%
Paoluzi (2000)⁴¹	Open	10	AZA refractory or intolerant UC (69% SD-UG)	6 months	12,5 mg/wk IM	Remission 60%, improvement 40%
Cummings (2005)^[55]	Retrospective	50	AZA refractory or intolerant UC	30 weeks (7–395)	20 mg/wk OS	Remission 42% Good response 54% Partial response 18%

Table 3. Adacolumn Studies in Steroid-Dependent Ulcerative Colitis (See Text)
Reference	Design	No. of patients	Treatment protocol	Adverse events	Results
Naganuma (2004)^[71]	Open	10 SD UC	once weekly session for 5 weeks	5%	Remission 60%
Hanai (2004)^[73]	Randomised unblind	69 SD UC	11 sessions over 10 weeks	22%	Remission 83%
Domenech (2004⁷⁰	Open	14 SD UC	once weekly session for 5 weeks	15%	Remission 62%
Kanke (2004)^[72]	Open	28 SD UC	10 sessions over 12 weeks	18%	68% steroid-free

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