Vulnerable patients: burning questions in IBD

An interesting session at ECCO dealt with the patients for whom there is sparce data to guide their treatment – experts in the field gave their guidance to delegates. Professor Jean-Frederic Colombel (New York, USA) comments on his practice in the elderly IBD patient.

Although the therapeutic arsenal for treating IBD is greater and more sophisticated than ever in 2017, there remain large groups of patients who present particular challenges for gastroenterologists in their everyday practice. One of the scientific sessions at the 12th Congress of ECCO was dedicated to the management of vulnerable patients, including pregnant women, elderly patients and patients diagnosed with cancer.

Pregnancy

Professor Janneke van der Woude described the pregnancy policy at the Erasmus Medical Centre in Rotterdam, under which all female IBD patients planning a pregnancy receive counselling, and disease remission is ideally achieved before conception. During the pregnancy the patient receives low-risk therapy to maintain remission; any relapse during pregnancy is treated without delay and an overall objective is to limit foetal drug exposure to the greatest possible extent. The risk of miscarriage or severe congenital malformations due to drug exposure is greatest during the first trimester; during later stages of the pregnancy the risk of birth defects is reduced but altered function or growth of normal organs may still occur.

Since the introduction of anti-TNF therapy in the late 1990s clinical experience has shown that use of anti-TNFs during pregnancy is associated with normal fertility and no increased risk of miscarriages during the first trimester, and no signs of an increased risk of birth defects.^1-4 A protocol of stopping therapy at week 22-24 of pregnancy to limit foetal exposure to anti-TNF showed no increased risk of relapse in women in sustained remission.^{5, 6} Although exposure to anti-TNF during pregnancy has not been linked to adverse outcomes, there have been case reports of adverse outcomes after live vaccination of the new-born child⁷ and of neonatal neutropenia.⁸ Based on the available clinical experience, the policy at Erasmus MC is to stop infliximab treatment in week 22 and adalimumab in week 33 in women in sustained remission only.

Experience with vedolizumab is limited and no firm recommendations can be given. The effect of vedolizumab on fertility is unknown, but MAdCAM-1 is expressed in the placenta during the first trimester.⁹ There have been 81 pregnancies and 11 spontaneous abortions entered in the post-marketing registry for vedolizumab.¹⁰ Likewise the risks of congenital malformations and infections in exposed newborns are unknown. The policy at Erasmus MC is to not initiate vedolizumab in IBD patients planning a pregnancy. If there are no alternative treatments the patient will be offered counselling, and if she agrees and remains in sustained remission vedolizumab will be continued until week 22 of pregnancy.

Elderly patients

In a talk on managing elderly patients with IBD, Professor Jean-Frédéric Colombel, from Mount Sinai in New York, pointed out the difficulty of making recommendations in this group – not least due to the lack of an agreed definition of ‘elderly’ and the fact that elderly patients typically will be excluded from randomised clinical trials. That said, there is clear evidence that azathioprine should be avoided in elderly patients due to the risk of cancers. A prospective cohort study in nearly 20,000 IBD patients showed that amongst patients aged over 65 years, the incidence rate of lymphoma was more than three times higher in patients on thiopurines compared with those who had never been exposed to thiopurines.¹¹ Similarly, patients over 65 years with thiopurine exposure also have significantly higher rates of non-melanoma skin cancer¹² and urinary tract cancer.¹³ Combination therapy with infliximab tilts the benefit-risk-balance even further against the use of thiopurines beyond the age of around 55 years.¹⁴

 

Less clear-cut is the question of whether elderly IBD patients should have different types of surgery. Elderly patients tend to cope less well with hospitalisation in terms of mortality and morbidity, especially following emergency surgery and elective surgery should therefore be preferred in this patient group.^{15, 16} Data on IBD patients undergoing restorative proctocolectomy shows that although elderly patients tend to stay longer in hospital and have more serious complications, their overall rates of complications and pouch failure were not different from younger patients.¹⁷ Such data highlights the need for a definition that focuses not on the age of patients but on their level of frailty, so that more specific recommendations can be made for vulnerable patients regardless of age.

Patients with cancer

The need for life-long immunosuppressive therapy to maintain remission in IBD poses a considerable challenge in patients who develop cancer. Although not much data has been published, there is general agreement that immunosuppressive therapy should be stopped in patients with newly-diagnosed cancer until the cancer is under control, except in cases of non-aggressive basal cell carcinoma.^{18, 19} If this is not possible, due to metastatic cancer or active IBD, quality of life should be prioritised and treatment with anti-TNF considered as published data has shown these to be well tolerated without worsening cancer progression.^{20, 21} In IBD patients with a history of cancer it is important to consider both the risk of new, second cancers and recurrence of cancer. Although a recent meta-analysis showed no increase in the rate of new and recurrent cancers in previous cancer patients who received anti-TNF therapy, immune modulators, or combination therapy²² it is still advisable to proceed with caution and consider the impact of impairing immune surveillance mechanisms in cancers with a lifelong risk of recurrence, such as some melanomas and breast cancers.²³ The 2016 ECCO guidelines state that immunosuppressive therapy for IBD should be delayed for up to 5 years after cancer treatment¹⁹ except in patients with severe IBD with no therapeutic alternative. All treatment decisions should be made in consultation with an oncologist.

References

 

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