Sub-Analysis of DIAMOND Study

K Watanabe et al. Clin Gastroenterol Hepatol 2018; 16: 542-9.

The DIAMOND study evaluated monotherapy with adalimumab (n=85) compared with combination therapy of adalimumab with azathioprine (n=91).

Key findings:

  • In this subanalysis of patients with moderate and severe Crohn’s disease (CD), endoscopic response (defined by SES-CD drop of at least 8 points or SES-CD <4) was significantly higher at week 26: 71.6% vs 54.4%. The OR for endoscopic response was 2.12 at week 26 with combination therapy.
  • At week 52 the endoscopic response difference was not statistically significant: 60% vs. 50%.
  • Similarly, mucosal healing was more common (but not statistically significant) in the combination group compared with monotherapy: 20.9% vs 103% at week 26, and 21.5% vs 12.2% at week 52.
  •  While not statistically significant, the combination group had ADA trough that was higher (7.6 compared with 6.5).

My take: The results described above for endoscopic responses and mucosal healing rates are depicted in figure 2 (I do not have a digital copy of figure or permission to use).  After one looks at this figure, depicting the data noted above, there certainly appears to be an advantage for the use of combination therapy in patients with moderate-to-severe CD.

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Three Studies Show the Benefit of Concomitant Therapy for Inflammatory Bowel Disease (Part 2)

Continued from yesterday…

The third study (HM Kansen et al. JPGN 2017; 65: 425-29) retrospectively (2009-2014) examined 162 children (with available data) with Crohn’s disease (CD) for the development of anti-infliximab antibody (ATI) while receiving either monotherapy or concomitant therapy. This was a collaborative study from the Kids with Crohn’s Colitis (KiCC) working group (Netherlands).  In the majority of their patients (222 of 229), IFX was initiated as step-up therapy. Key findings:

  • 15% developed ATIs
  • 6 of 62 (10%) developed ATIs while receiving ongoing concomitant immunosuppression
  • 11 of 81 (14%) developed ATIs after receiving early concomitant immunosuppression (median of 6.2 months of concomitant immunosuppression followed by IFX monotherapy) 10 of 11 who developed ATIs  within the first 12 months, compared to 1 of 26 (4%) after 12 months.
  • 8 of 19 (42%) developed ATIs on IFX monotherapy

In their discussion, the authors note concerns regarding the safety of thiopurines. However, they point out that “the benefit of combination therapy (reduction of ATI formation) relative to IFX monotherapy should outweigh the risk of serious infections and malignancies to achieve an optimal treatment strategy for paediatric CD.” The authors: “combination therapy for approximately 12 months from initiation of IFX, followed by IFX monotherapy, may be equally effective alternative to continuous combination therapy.”

Overall, the totality of the evidence favors combination therapy for most patients with CD.  Yet, there is wide variation in clinical practice. As I was thinking about this, I came across a recent commentary: “The Power of Regret” (J Groopman, P Hartzband. NEJM 2017; 377: 1507-9).  The authors note that “disappointment is an unavoidable aspect of making difficult choices…but disappointment is not associated with self-recrimination and thus differs notably from regret.”  They indicate that “process regret” occurs when patients do not consider information about all available choices before making a decision.  I wonder if many patients/families fear using concomitant therapy because they worry they will regret the decision if a complication occurs.  Perhaps, working with all available information, some reluctant patients/families will feel better about their decision if the process for their decision was thorough, considering the risks/benefits of the treatment but also the risks/benefits of not choosing the treatment. .

My take: Overall, for most pediatric patients with CD, to date, concomitant therapy has been the most effective treatment.  More prospective studies are needed to determine more conclusively the benefit and optimal duration/timing of combined therapy, particularly with the more frequent use of therapeutic drug monitoring. Also, as will be noted in future posts from annual meeting, thiopurine use is declining.

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Three Studies Show Benefit of Concomitant Therapy for Inflammatory Bowel Disease (Part 1)

In the first study (J Cheng et al. Inflamm Bowel Dis 2017; 23: 1762-73), the authors retrospectively reviewed 148 children (113 with Crohn’s disease, 35 with ulcerative colitis). 90 patients received concomitant therapy (infliximab with either a thiopurine [n=67], methotrexate [n=23]) and 58 received infliximab monotherapy. Key findings:

  • Concomitant therapy >6 months  significantly lowered the risk of secondary loss of response in Crohn’s disease (CD) (HR =0.39) compared to monotherapy.   A similar trend was noted with ulcerative colitis (UC) but did not reach statistical significance.
  • Steroid-free remission rates at 1 year were 78% for CD patients with concomitant therapy compared with 54% on monotherapy
  • Among primary nonresponders, 67% of CD patients and 75% of UC patients were receiving IFX monotherapy.
  • No differences in adverse events were evident between patients receiving monotherapy compared with concomitant therapy. One patient (receiving azathioprine) developed a follicular lymphoma; this patient was well 10 years later.

The second study (Y Qui et al. Clin Gastroenterol Hepatol 2017; 15: 1359-72) was a systemic review of 35 studies that met the authors’ inclusion criteria. In total, 6790 patients with inflammatory bowel disease were enrolled in these studies. This study looked at multiple anit-TNF agents including infliximab, adalimumab, certolizumab, and golimumab. Key finding:

  • Antidrug antibodies were reduced by 51% in patients receiving concomitant therapy
  • Conclusion from authors: “concomitant use of immunomodulators should be considered in patients treated with anti-TNF treatment.”

My take: Overall, for most pediatric patients with CD, to date, concomitant therapy has been the most effective treatment.  More prospective studies are needed to determine more conclusively the benefit and optimal duration/timing of combined therapy, particularly with the more frequent use of therapeutic drug monitoring.  Also, as will be noted in future posts from annual meeting, thiopurine use is declining.

More on this topic tomorrow.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.