Body composition and functional capacity in patients with Crohn’s disease using Infliximab

Rationale: the use of anti-TNFα therapy, such as Infliximab (IFX), in patients with Chron’s disease (CD) can lead to changes in body composition. Objective: to evaluate the body composition and functional capacity of patients with CD. Method: Cross-sectional study with patients with CD in clinical remission using IFX. For anthropometric evaluation, it was measured: weight, height and waist circumference; functional capacity by the hand grip strength test and body composition by bioelectric impedance. After that, the fat-free mass index and body fat index were calculated. Continouns variables were analyzed by Pearson or Spearman coefficient. For the multiple linear regression model, the time of use of IFX was used as a dependent variable and waist circumference, fat-free mass index, phase angle and handgrip strength were used as independent variables. Results: forty-three patients were evaluated, with an average of 43.1± 13.5 years of age. Of the total, 44.2% were overweight and 44.2% had increased waist circumference, 58.1% were classified with high to very high fat-free mass, 30.2% were below the adequacy parameter for fat-free mass index and 11.6% had reduced functional capacity. Conclusion: overweight, as well as increased waist circumference and body fat, is common in CD patients in clinical remission using Infliximab. Most patients had preserved functional capacity, however there wasn’t association with time of use of IFX.


INTRODUCTION
Crohn's disease (CD) is an inflammatory bowel disease (IBD) with transmural involvement that can affect from the mouth to the anus 1 . Traditionally it was considered a disease of developed and "Westernized" nations, but recent studies have shown it increased in incidence in rapidly industrializing countries in Asia, Africa and Australasia. In Brazil, there is an increase in the incidence and prevalence of CD over time and it's higher in the developed states of the country as compared with the states with the lowest development index in Brazil 2 .
Although IBD envolves with malnutrition and weight loss, currently overweight and obesity are the most Rev. Ciênc. Méd. Biol., Salvador, v. 22, n. 1, p. 52-57, jan./abr. 2023 frequent nutritional disorders in these population, especially in the remission phase of the disease 1,3,4 . One of the possible factors for this occurrence is the introduction of anti-TNF-α therapy, such as infliximab (IFX) 5 .
When compared with conventional therapy, IFX treatment promotes sudden and prolonged regulation of inflammation, stimulating mucosal healing. In this way, it promotes the recovery of nutritional status with weight gain and increase in strength and muscle mass [6][7][8][9][10] . However, after six months of treatment, patients have a significant increase in abdominal obesity and body fat 7 .
Changes in body composition such as excess weight and reduced muscle mass increase the chances of loss of response to anti-TNF-α therapy in patients with IBD, since they alter the pharmacokinetics of the drug 11,12 . Therefore, the aim of the study was to evaluate the body composition and functional capacity of patients with CD in clinical remission using IFX. This study will serve as a basis to substantiate the nutritional approach, contributing to the effectiveness of drug therapy and better clinical prognosis for patients.

ANTHROPOMETRIC ASSESSMENT
Body mass was measured in the morning on an anthropometric scale with a maximum capacity of 150 Kg and a variation of 100 g (Welmy®). The height was measured using a mobile stadiometer attached to the scale with millimeter accuracy.
Body Mass Index (BMI) was calculated. Cut-off points established by the World Health Organization were considered 14 .
Waist circumference was measured using a flexible anthropometric tape with an accuracy of 0.1 cm (Cescorf®). The cut-off points established by the WHO were adopted (women: ≥ 80 cm, men: ≥ 94 cm) 14 .

ASSESSMENT OF BODY COMPOSITION
To assess body composition, the Biodynamics 450® bioelectric impedance device with 800µA and 50 KHz was used. Telephone contact was made the day before the consultation for guidance on how to perform the exam.
From resistance (R) and reactance (Xc) data, fat-free mass 15 , body fat 16 and phase angle 17 were calculated.
For the calculation of the fat-free mass index and body fat index, the values of fat-free mass and body fat, respectively, were divided by height squared, with the body mass in kilograms and the height in meters. The cut-off points of Kyle et al. 18 (2005) were used to assess fat-free mass index (women: ≤ 15 kg/m 2 , men: ≤ 17.4 kg/m 2 ) and body fat index (women: ≥ 8.2 kg/m 2 , men:

FUNCTIONAL CAPACITY ASSESSMENT
To evaluate the functional capacity, the handgrip strength was measured using the Jamar® analog hydraulic dynamometer.
Three consecutive measurements were taken with the non-dominant hand with a 30-second rest interval between each measurement 19 . The average value between the three attempts was assumed. The reduction of muscle mass was defined by handgrip strength < 5th percentile by age and sex according to the cutoff points of Budziarek, Duarte, Barbosa-Silva 20 (2008).

STATISTICAL ANALYSIS
For statistical analysis, SPSS version 22.0 was used. The Shapiro-Wilk test was considered to evaluate the normality condition of the variables. Variables with normal distribution were described in average and standard deviation and non-normal distribution in median or con-  It was identified that 30.2% (n=13) presented low value for fat-free mass index and 11.6% (n=5) -all were male -presented reduced functional capacity (Table 2).

DISCUSSION
The results of this study indicate that overweight and obesity and abdominal obesity are common, as well as increased body fat in patients with CD in clinical remission and using IFX. It also highlights that about 30% of these patients had a reduction in fat-free mass.
The high prevalence of overweight and obesity found in this study is consistent with the current scenario in which obesity is the most frequent nutritional disorder in patients with IBD 3,4,21,22 . It is known that between 15% and 40% of IBD population are obese 21 .
Ramos et al. 23 (2019) also found a high prevalence of overweight and abdominal obesity in patients with CD in clinical remission and in therapy with anti-TNF-α, the frequency of overweight and obesity (BMI ≥ 25 kg/m 2 ) was 55.7% in patients with CD versus 41.2% in the control group of healthy individuals (p < 0.0001). In the study of Magro et al. 24 (2018), the prevalence of overweight and obesity in patients with CD was 42%, where 67% were using anti TNF alpha therapy. This is similar to the findings in our study.
Probably, patients with CD in remission and using IFX are one of the first affected by the nutritional transition, since symptom control and reduction of catabolism associated with inflammation are maintained for a longer period of time when compared to conventional drug therapy 8 . In addition to the drug's previously mentioned physiologic action, a sedentary lifestyle and poor eating habits can contribute to weight gain. The adoption of western nutritional habits characterized by an overall higher calorie consumption that is primarily made up of sugar, refined carbs, animal proteins, and ultraprocessed foods has been associated with higher risk of obesity 25 .
Associated with increased body fat, about 30% of patients presented low fat-free mass index. Similar results were observed by Back et al. 26 (2017) in which the average fat-free mass index in patients with CD in clinical remission (n=30) was 18.5 ± 2.8 kg/m 2 . The increase in obesity in IBD patients coincides with the increase in rates of sarcopenia, which is defined as low lean mass (myopenia) and loss of strength 27,28 . A systematic review reported that 42.0% of IBD patients were sarcopenia and this condition affects the prognosis, such as rehospitalization, death and several infections 29,30 . Overweight and sarcopenia may influence the response to biological therapy by altering the pharmacokinetics of the drug 11,25 .
In a meta-analysis study with 4,589 IBD patients on anti-TNF-α therapy, it was found that IBD patients with obesity had a 19.5% greater chance of loss of response to anti-TNF-α therapy 11 . As well as obesity, myopenia in patients with CD, when inserted in the multivariate analysis with albumin, was associated with loss of primary response to anti-TNF-α therapy within 6 months after the first administration, not including patients who stopped treatment due to intolerance to the therapy 12 .
Although the body composition was altered, only 11.6% of the patients had reduced functional capacity. The use of IFX may be associated with anabolism and consequent increase in strength and muscle mass 7 The fat-free mass has a positive correlation with the phase angle in patients with CD, this being greater in patients in remission of the disease 32 . The average phase angle found was similar to the findings of Cioffi et al. 32 (2019) in the group of patients with CD in biological therapy.
The phase angle is an indicator of good nutritional status 33 . In our study, the mean phase angle in both sexes indicate absence of malnutrition according to the cutoff points suggested to patients with CD reported by Peng et al. 33 (2022) . Emerenziani et al. 8 (2017) found greater phase angle in patients with CD in clinical remission on IFX treatment compared to patients on conventional therapy.
In this study, it was found that the longer the time of use of IFX, the higher the BMI and waist circumference. Despite the beneficial effect on the recovery of nutritional status, which is already observed from the beginning of the IFX induction protocol until the maintenance 8,9 . Santos et al. 7  This study has limitations such as the reduced number of participants. However, the use of anthropometry associated with bioelectric impedance can help in the understanding of body changes in patients with CD using IFX. In addition, the use of bioletric impedance has as advantages in clinical practice: the low cost and practicality.
Since the imbalance in body composition can influence the loss of response of biological therapy and the development of chronic non-communicable diseases, it becomes essential to substantiate the nutritional approach.

CONCLUSION
The high frequency of overweight, as well as the increase in body fat, signaled by the increased waist circumference are related to the time of use of IFX in patients with CD in clinical remission. Most patients had preserved functional capacity, however there wasn't association with time of use of IFX.