A. Atanassova, A.C. Georgieva, M. Mirchev
Medical University – Varna- Bulgaria, University Hospital St. Marina- Clinic of Gastroenterology, Varna, Bulgaria
Background
Despite the timely commencement of the biological treatment, only about 30% will respond to it, and about 1/3 will lose the initial anti-TNF (tumour necrosis factor) response.
Methods
We retrospectively studied the data of 69 Crohn’s disease (CD) patients who started biological treatment with anti-TNF-ADA/ IFX. We excluded patients who are primary nonresponders to IFX/ADA. In patients with induction of clinical response, we investigated and analysed the frequency of subsequent loss of response (LOR) to IFX/ADA. We analysed the possible risk factors that have led to LOR.
Results
Of the 69 patients undergoing biological treatment, 71.01% achieved a clinical response during the course of the follow-up. There is a correlation between the presence of a clinical response and the CD course- x2 = 10.78, p = 0.013, ρ = 0.241, (p = 0.046). Inflammatory phenotype (В1) manifestation among our patients is a factor for achieving a clinical response OR = 3.68 (1.116–11.73), p = 0.021, whereas the presence of a penetrating form is a risk factor for the lack of response OR = 6.13 (1.29–29.01), p = 0.019. The presence of intestinal complications is a risk factor for the lack of response- OR = 3.2 (1.61–6.37), p = 0.001. During the course of the follow-up in 30.61% of cases, we observed LOR (men/women - 86.66%/13.33%, p < 0.05 (p = 0.02), in 60.00 % this was between 1–2 years, on average 20.62 ± 13.07 months from the start of the biological treatment. A total of 46.66% of patients required treatment with another anti-TNF drug due to secondary loss of response. A total of 50% of patients needed a reduction of the dose interval. Over 50.00% of those with LOR have an extensive disease (L3). A total of 40% have В1 and 33% have stricturing (В2) and penetrating (В3) phenotypic expression. In 26.66%, we observed progression of the disease range, and in 46.66% of patients - intestinal complications, none of whom had subsequent surgery. In 21.42% of LOR patients there is a combination of intestinal complications and progression according to disease localisation. 93.33% of CD patients with LOR have a persistence of extraintestinal manifestations (EIMs); those with two or three EIMs predominate. We discovered that gender was a risk factor for loss of response, OR = 8.36 (1.16–60.26), p = 0.005, as is the combination of В2 and В3 form of the disease OR = 14.72 (2.47–87.79), p = 0.003. Patients who lost response during the course of treatment had higher mean faecal calprotectin, CDAI and CRP prior to the initiation of the anti-TNF therapy.
Conclusion
The high activity of the disease measured with CDAI, faecal calprotectin and CRP, male gender, the combination of penetrating and stricturing form during the course of the disease are all risk factors for the loss of response.
