One Proposal to Reduce Thiopurine Combination Therapy

A recent review (X Roblin et al. Inflamm Bowel Dis 2016; 22: 1496-1501) provided a useful review of thiopurine/biologic combination therapy.  The part of this review that I found intriguing was their Figure 3: “Proposed algorithm that may guide drug discontinuation or de-escalation in patients with IBD who achieved sustained deep remission while on combination therapy.”

  • In those (in sustained deep remission) with an infliximab trough level >5 mcg/mL, this algorithm recommends discontinuation of thiopurine.
  • In those with an infliximab trough level 3-5 mcg/mL and with 6-TGN >250, this algorithm recommends reduction of thiopurine to obtain 6-TGN level >125.
  • In those with an infliximab trough level <2 mcg/mL and with 6-TGN >250, this algorithm recommends discuss stopping infliximab.

The authors acknowledge that this algorithm has not been studied and “needs to be investigated in prospective trials specifically addressing this issue.”

My take: Until more studies emerge, the best way to balance control of IBD and minimize drug toxicity remains uncertain.

Unrelated references:

  • “Crohn’s disease of the ileoanal pouch” AL Lightner et al. Inflamm Bowel Dis 2016; 22: 1502-8.
  • SZ Koh et al. Inflamm Bowel Dis 2016; 22: 1397-1402. This reference describes clinical factors associated with development of Crohn’s disease in patients with IBDU who have undergone ileal pouch (e.g. younger age).

Related blog posts:

Arthur Ravenel Jr Bridge

Arthur Ravenel Jr Bridge

Sticky Decisions with IBD Therapy – When an Infection or Malignancy Develops

A recent review article provides advice for management of biologics and immunomodulators when an infection or malignancy develops (Inflamm Bowel Dis 2014; 20: 926-35).  Serious infections are noted in 3-5% of adults receiving either thiopurines or anti-tumor necrosis factor agents (anti-TNFs); less than 0.1% of adults develop treatment-related lymphoma.  The recommendations are provided in 5 separate tables.

Table 1 addresses the issue of bacterial infectionsFor mild infections, the authors recommend that thiopurines (azathiopurine, 6-mercaptopurine) as well as anti-tumor necrosis factor agents (infliximab, adalimumab, certolizumab, golimumab) be continued.  Examples of these ‘mild’ infectious included E. coli UTI and strep pharyngitis.  For severe bacterial infections (eg. pneumococcal pneumonia), for both these therapies, the authors recommend: “stop, but may restart once treated.”  For bacterial opportunistic infections (eg. mycobacterium), for latent infections, “do not start until 2 to 4 wk INH” whereas for active infections, the authors recommend (for anti-TNFs) “stop, only restart after full treatment, and if IBD is severe.”

  • Table 2 addresses fungal infections.
  • Table 3 addresses viral infections (eg. CMV, EBV).  For EBV, the authors recommend stopping thiopurines and not restarting in male patients.
  • Table 4 addresses malignancy: solid tumors, hepatosplenic T-cell, EBV-associated lymphoma, and lymphoproliferative lymphoma.
  • Table 5 addresses skin cancers.

Towards the end of the review, the authors provide some context for the risks with thiopurines and anti-TNFs.  “The majority of side effects associated with thiopurines and anti-TNFs are mild, self-limited and reversible…the risk of a lymphoma developing on AZA/6-MP (4/10,000 patient-years) is comparable with the lifetime risk of dying from drowning (1/1112) or dying in a bicycle accident (1/5000).  The risk is much less than the risk of dying in an automobile accident (1/108).  Patients are willing to accept risks..if their disease is severe and the chance of a clinical response outweighs the risk.”

With regard to dual therapy, the authors note, “it has been our practice to lower the concomitant AZA/6-MP in patients on combination therapy with anti-TNF and then to stop the thiopurine in patients in deep remission for 3 years. However, this decision must be individualized, and for patients with severe, disabling disease, we generally do not alter treatment.”

Bottomline: This is a useful advice/handy reference for the sticky situation of managing IBD in the face of infections and malignancy.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.