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Thalomid induces, maintains remission in refractory pediatric UC
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Results from a pilot randomized controlled trial showed Thalomid induced and maintained clinical remission in children and adolescents with ulcerative colitis refractory or intolerant to other immunosuppressives.
Marzia Lazzerini, DTMH, MSc, PhD, from the Institute for Maternal and Child Health IRCCS, “Burlo Garofolo,” in Trieste, Italy, and colleagues, performed a double-blind trial involving 26 children aged 2 [to] 18 years with active ulcerative colitis despite multiple immunosuppressants who were randomly assigned to receive 1.5 to 2.5 mg/kg Thalomid (thalidomide, Celgene) per day or placebo for 8 weeks. Nonresponders in the placebo group received an additional 8 weeks of thalidomide in an open-label extension, and all responders were prospectively followed up for at least 52 weeks.
At week 8, clinical remission defined by the Pediatric Ulcerative Colitis Activity Index was achieved by 83.3% of the thalidomide group compared with 18.2% of controls (RR = 4.5; 95% CI, 1.2-16.4; number needed to treat [NNT], 1.5; 95% CI, 1.1-4). Clinical response at 8 weeks was achieved by 66.6% of the thalidomide group compared with 18.2% of controls (RR = 3.7; 95% CI, 1-13.7; NNT, 1.5; 95% CI, 1.18-8.14).
In the open-label extension, 72.7% of 11 placebo group nonresponders achieved remission at 8 weeks (RR = 4; 95% CI, 1.1-14.7; NNT, 1.8; 95% CI, 1.1-8.1).
Mean duration of clinical remission was 135 (95% CI, 32-238) weeks with thalidomide compared with 8 (95% CI, 2.4-13.6) weeks with placebo (P < .0001). Mucosal healing was achieved in 47% of 17 patients at week 12 and in 83.3% of 12 patients at week 52.
The cumulative incidence of severe adverse events resulting in treatment suspension was 3.1 per 1,000 patient-weeks (95% CI, 1.5-6), and the most common adverse events included peripheral neuropathy and amenorrhea.
“In this pilot RCT on extremely severe cases refractory to immunosuppressive therapy, the use of thalidomide versus placebo in children and adolescents resulted in improved clinical remission at 8 weeks of treatment and long-term maintenance of remission with an open-label follow-up,” the researchers concluded. “More studies on thalidomide in patients with inflammatory bowel diseases should be conducted to definitively determine efficacy and safety of this treatment.”
In an accompanying editorial, Athos Bousvaros, MD, MPH, from Harvard Medical School and the Inflammatory Bowel Disease Center at Boston Children’s Hospital, wrote that his initial impression of the findings from this study by Lazzerini and colleagues, as well as their previous trial of thalidomide in Crohn’s disease, were “too good to be true,” but comparable response rates in Crohn’s disease have been reported by other investigators, while data on ulcerative colitis is more limited. “Thus, the authors’ conclusion that ‘these findings require replication in larger clinical studies’ is correct,” he wrote. “However, such studies are exceedingly difficult to do on an old drug, especially one with the stigma attached to thalidomide. I suspect that the primary focus on drug development will focus on newer small molecules and biologics, and this potentially useful medication may be left on the sidelines.”
In a reply to Bousvaros’s editorial, Lazzerini and colleagues agreed there is a need for further research to identify new therapies for long-term treatment of IBD with good safety profiles and sustainable costs. However, they maintained that “the safety profile, although more studies are needed to further confirm the existing evidence, seemed to be acceptable if we consider that the cases treated were refractory/intolerant to other drugs.
“In the patients’ interest, the decision of whether to use thalidomide (as for any other drug) should be based on the most up-to-date evidence and not on old stigmas,” they added. – by Adam Leitenberger
Disclosures: The researchers and Bousvaros report no relevant financial disclosures.
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