Tag Archives: PUCAI

More on Adalimumab (Humira) in Pediatrics

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A recent ‘observational cohort’ study (Cozijnsen M, et al. JPGN 2015; 60: 205-10) provides more information regarding the use of adalimumab in pediatrics.  The authors attempted to identify all Dutch patients <18 years of age with Crohn’s disease who received adalimumab after infliximab therapy.  Excluded patients were those with “bad treatment adherence,” conflicting comorbidity, and previous participation in prospective study by Hyams et al Gastroenterol 2012; 143: 365-74 (Related blog post: Adalimumab for children with Crohn’s disease | gutsandgrowth).

Key findings:

  • 53 patients met the inclusion criteria.  12 received monotherapy with adalimumab; cotherapy in 21 with thiopurines, 11 with methotrexate, 7 with steroids, and 2 with enteral nutrition.
  • Median followup was only 12 months.
  • Remission noted in 34 (64%) patients based on either wPCDAI or PGA (physician global assessment) after a median of 3.3 months.  Remission was durable in 50% of these patients for 2 years.
  • Adalimumab failure was noted in 18 (34%).  Only 3 patients in this study were primary infliximab nonresponders and only 1/3 responded to adalimumab.
  • One serious adverse event (infection) was reported.

One weakness of this study (& many others) is its reliance on clinical disease activity indices rather than more precise measures of mucosal healing.

Take-home point: This small study provides some information about the utility of adalimumab in clinical practice in pediatrics.  As noted in other studies, those with a loss of response to infliximab, rather than primary nonresponders, appear to have a more favorable response to adalimumab. In addition, the glaring weakness in this study (i.e. small number of participants) validates the rationale behind efforts like ImproveCareNow which can generate information quickly from a large patient population.

Related study: “Levels of Drug and Antidrug Antibodies are Associated with Outcome of Interventions After Loss of Response to Infliximab or Adalimumab.” Yanai H, et al. Clin Gastroenterol Hepatol 2015; 13: 522-30. Retrospective study of 247 adult and pediatric patients. Key findings:

  • Patients with adequate trough levels (>4.5 mcg/mL for adalimumab, >3.8 mcg/mL for infliximab) “identified patients who failed to respond to an increase in dosage or a switch to another anti-TNF agent with 90% specificity.”
  • “Levels of antibody against adalimumab >4 mcg/mL-eq or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity.” These patients were likely to benefit by switching to an alternative anti-TNF.

Related study: Clin Gastroenterol Hepatol 2015; 13: 539-47.  Trough levels of infliximab (>3 mcg/mL) at week 30 was associated with improved outcomes, including mucosal healing and corticosteroid-free remission.

Briefly noted from ImproveCareNow: Dotson JL et al. “Feasibility and Validity of the Pediatric Ulcerative Colitis Activity Index in Routine Clinical Practice.” JPGN 2015; 60: 200-04.  This study, with 2503 patients, found that the PUCAI was completed in 96% if visits.  The PUCAI correlated with PGA chain scores.

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Predicting Remission in Pediatric Ulcerative Colitis

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Trying to offer realistic information to families on the long-term success of infliximab (Remicade) for pediatric ulcerative colitis has been difficult due to a limited amount of data.  In addition, many studies have a number of limitations which can make it difficult to extrapolate to a less-selected population (According to the study which you would never qualify for …).

A recent post hoc analysis (Clin Gastroenterol Hepatol 2013; 11: 1460-65) from 51 children (age 6-17 years) provides some insight into this issue.  The authors used data collected prospectively during the T72 clinical trial (Clin Gastroenterol Hepatol; 10: 391-99 -reviewed in blog post: Infliximab for children with Ulcerative Colitis | gutsandgrowth).

Results:

  • Week 8 PUCAI scores best predicted which patients would be in steroid-free remission after 1 year of treatment: 9 of 17 (53%) with scores <10 points were in sustained remission compare with 4 of 20 (25%) with scores ≥10.
  • Week 8 PUCAI outperformed mucosal healing in predicting remission.

Key points:

  • PUCAI may have outperformed mucosal healing because the latter can lag behind clinical response.  Furthermore, mucosal healing is more subjective with less interobserver reliability.
  • In patients with known inflammatory bowel disease, endoscopic assessment remains important in several situations: condition or reason for symptoms is in question (eg. exclude irritable bowel symptoms or medication-induced symptoms), acute severe colitis not responding to 3-day treatment with intravenous steroids to exclude superinfection, and to assess mucosa before major treatment changes “such as when starting or stopping biologics and before referral for colectomy.”

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