Intest Res.  2019 Jul;17(3):340-348. 10.5217/ir.2019.00012.

Ustekinumab is effective in biological refractory Crohn's disease patients–regardless of approval study selection criteria

• Saman S
• Goetz M
• Wendler J
• Malek NP
• Wehkamp J
• Klag T

• KMID: 2454742
• DOI: http://doi.org/10.5217/ir.2019.00012

Abstract

BACKGROUND/AIMS
Ustekinumab is effective in active Crohn's disease. In a retrospective study, we assessed the clinical outcome in nonresponders to anti-tumor necrosis factor therapy, and/or conventional therapy and/or the α4β7-integrin inhibitor vedolizumab. As approval study populations do not always reflect the average "real world" patient cohort, we assessed weather patients who would not have qualified for approval studies show similar outcomes.
METHODS
Forty-one patients with mild to severe active Crohn's disease were treated with ustekinumab (intravenous 6 mg per kg/body weight) followed by subcutaneous ustekinumab (90 mg) at week 8. Depending on the clinical response maintenance therapy was chosen every 8 or 12 weeks. Clinical response was defined by Crohn's Disease Activity Index (CDAI) decline, decline of stool frequency or clinical improvement. Inclusion criteria for approval studies were assessed.
RESULTS
The 58.5% (24/41) showed clinical response to ustekinumab. The 58.3% of this group (14/24) achieved clinical remission. Clinical response correlated significantly with drop of stool frequency and improvement of CDAI score. The 39 out of 41 patients had no side effects and we observed no serious infections. About a third of our patients would not have met ustekinumab approval study criteria. However, patients who did not meet study criteria showed clinical improvement numerically in the same range compared to patients who would have qualified for approval studies.
CONCLUSIONS
Ustekinumab is effective, safe and well tolerated in a highly therapy refractory patient cohort. Even though a reasonable number of patients did not meet ustekinumab approval study criteria, approval study results seem to be representative to the overall patient cohort.

Keyword

Crohn disease; Ustekinumab; Biological therapy

MeSH Terms

Biological Therapy
Cohort Studies
Crohn Disease*
Humans
Necrosis
Patient Selection*
Retrospective Studies
Ustekinumab*
Weather
Ustekinumab

Figure

• 

  Fig. 1. Overall response and nonresponse towards ustekinumab. Shown are proportion of responders and nonresponders (A) and the characterization of primary responders (B). Clinical response was defined by either CDAI decline of more than 100 points, improvement as reported by patient’s well-being and physicians global assessment. Clinical remission was defined as CDAI score of less than 150 points. PR, primary response; PNR, primary nonresponse; SNR, secondary nonresponse (response that was not maintained).

• 

  Fig. 2. Follow-up of hemoglobin, stool frequency, CDAI, and CRP levels during treatment with ustekinumab. The graphics show the development of hemoglobin (A), stool frequency (B), CDAI (C), and CRP (D) during treatment with ustekinumab in the primary responder group from week 0 (before 1. application) to week 32 (after 3. application). Dotted line in panel C represents the threshold of flare-ups (CDAI score >220). Dotted line in panel D represents normal CRP value <0.5 mg/dL. Statistical relevance of the results was assessed performing the paired t-test. P≤0.05 was considered to be statistically significant. a P<0.05, b P<0.01, c P<0.001, d P<0.0001.

• 

  Fig. 3. Response with respect to prior biological treatment. (A) Depicts the proportions of response with respect to prior biological treatment. Patients who had not been treated with a biological were defined as biological naive. (B) Focuses on patients with prior anti-TNF therapy. (C) Depicts response and remission of the primary responders. Clinical response was defined by either CDAI decline of more than 100 points, improvement as reported by patient’s well-being and physicians global assessment. Clinical remission was defined as CDAI score of less than 150 points. PR, primary response; PNR, primary nonresponse; SNR, secondary nonresponse (response that was not maintained).

• 

  Fig. 4. Response with respect to prior therapy with vedolizumab and anti-TNF. (A) Shows response rate with respect to prior therapy with vedolizumab and anti-TNF and (B) characterizes the responders of this group. Clinical response was defined by either CDAI decline of more than 100 points, improvement as reported by patient’s well-being and physicians global assessment. Clinical remission was defined as CDAI score of less than 150 points. PR, primary response; PNR, primary nonresponse; SNR, secondary nonresponse (response that was not maintained).

• 

  Fig. 5. Comparison of patients qualifying for approval studies or who would not have qualified. Shown are the proportions of patients who would not (A) and would qualify (B) for the published ustekinumab approval studies and their response rates towards ustekinumab in our patient cohort. Clinical response was defined by either CDAI decline of more than 100 points, improvement as reported by patient’s well-being and physicians global assessment. Clinical remission was defined as CDAI score of less than 150 points. PR, primary response; PNR, primary nonresponse; SNR, secondary nonresponse.

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