Historia natural y calidad de vida de los pacientes con enfermedad inflamatoria intestinal tratados con inmunosupresores tiopurínicos

Abstract

Inflammatory bowel disease (IBD) is chronic disorder that causes inflammation of the digestive tract. IBD patients, both ulcerative colitis (UC) and Crohn's disease (CD), have an impaired perception of their health-related quality of life (HRQoL). Disease activity is the main factor associated with impaired HRQoL. Thiopurines, azathioprine (AZA) or 6-mercaptopurine (6MP), are used in multiple scenarios in IBD, mainly to maintain the patient in remission. The effect of thiopurines on HRQoL in patients with IBD has been controversial. _x000D_ The aims of this thesis were to evaluate the HRQoL in patients with IBD treated with thiopurines and assess the short- and long-term impacts of the treatment on HRQoL and to know the influence of objective variables (mucosal healing) on the HRQoL. _x000D_ Ninety-two consecutive patients who started treatment with thiopurines were prospectively included. Evaluation of HRQoL was performed at months 0, 6, and 12 using two questionnaires, the Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Clinical activity was assessed with the CDAI (Crohn’s disease activity index) in CD-patients and with the Mayo Clinic score in UC-patients. Mucosal healing (MH) was considered in the absence of ulcers in CD-patients. In patients with UC, MH was considered in case of Mayo endoscopy subscore of 0-1. In those patients treated to prevent the postoperative recurrence of CD a Rutgeerts score of 0 was considered mucosal healing. _x000D_ Fifty eight (63%) patients had an adverse effect, the most frequent was gastrointestinal toxicity in 30 (33%) patients, leading to treatment withdrawal in 15 (50%). Gastrointestinal toxicity was more frequent in female gender. Fourteen patients intolerant to AZA were treated with 6MP, of them, 5 (36%), tolerated 6MP. _x000D_ Fifty patients were included with CD (patients treated to prevent the postoperative recurrence (POR) are reported separately). At baseline HRQoL, both assessed with IBDQ and SF-36, were impaired compared with a background population. The use of steroids was associated with worse HRQoL. Thirty (60%) and 23 (54%) patients were in remission per protocol at 6 and 12 months respectively. All dimensions of IBDQ and SF-36 scored better at 6 and 12 months and were comparable to Spanish general population. Nine of 20 (45%) at six months and 11/20 (55%) at 12 months achieved MH. HRQoL was better in those patients with MH. _x000D_ Twenty four patients were included with UC. At baseline IBDQ and SF-36 scored worse if compared with reference population. Eight (33%) and 12/17 (54%) patients were in remission per protocol at 6 and 12 months respectively. Most of domains of IBDQ and SF-36 experienced a slightly improvement but they did not reach statistical difference and were worse than Spanish general population. Three of 13 (23%) at six months and 6/12 (50%) at 12 months achieved MH. HRQoL was better in those patients with MH. _x000D_ Eighteen patients were treated to prevent POR. At baseline IBDQ and SF-36 scored worse if compared with reference population. C reactive protein (CRP) and CDAI correlated with worse HRQoL. Seventeen (94%) and 10/12 (83%) were in remission per protocol at 6 and 12 months respectively. All dimensions of IBDQ and SF-36 scored better at 6 and 12 months and were comparable to Spanish general population. Baseline CRP correlated with higher improvement in HRQoL. Six of 11(55%) at six months and 4/7 (57%) at 12 months achieved MH per protocol. HRQoL was independent of the MH. _x000D_ Conclusions: Gastrointestinal toxicity was the most frequent side effect, mainly in women; 6MP is effective in near 40% of AZA-intolerant patients. Thiopurines have a positive and long lasting impact on HRQoL of IBD patients. Patients with MH had better HRQoL except during the prevention of POR.

Date of Award	3 Oct 2016
Original language	Undefined/Unknown
Awarding Institution	Vall d'Hebron University Hospital (HUVH)
Supervisor	Pilar Nos Mateu (Director), Fernando Azpiroz Vidaur (Tutor) & Miquel Àngel Gassull Duró (Director)