CD is an inflammatory disease that can affect any part of the digestive tract, including the mouth, anus, and esophagus. Diarrhea, abdominal pain, anal hemorrhage, and weight loss are among the digestive symptoms of CD, as is skin lesions beyond the gastrointestinal tract. CD is characterized by recovery and recurrence periods (1, 2). According to the World Gastroenterology Organization, CD incidence is 29 out of every 100,000 people in the Middle East, while its incidence is 5 per 100,000 (3).

Surgical admissions, living with a stoma and short bowel syndrome followed by removing an extensive portion of the intestine, and indirect expenses such as lost income, productivity, and leisure time are all linked to HRQoL in CD patients (4).

HRQoL shows a disease's functional influence and is one of the most critical issues in chronic diseases (4). Clinical, psychological, socio-demographic, and treatment-related aspects are all important drivers of HRQoL in CD illness (5, 6). Although disease activity is an important determinant of HRQoL in CD disease, even asymptomatic individuals have lower HRQoL than the general population, demonstrating the importance of other factors in CD patients' HRQoL (7, 8). A detailed grasp of the above-mentioned effects on HRQoL can play a significant role in clinician decisions, particularly when deciding between two therapeutic procedures with the same clinical impact or while treating asymptomatic patients (9). The Crohn's Disease Activity Index (CDAI) is commonly used in clinical trials to quantify the clinical activity of CD disease, but it cannot adequately measure disease burden (10). As a result, evaluating the repercussions of this condition requires more than only monitoring clinical activity. It is also critical to determine patients' HRQoL (11).

According to a study of the literature, the majority of HRQoL research has been conducted on CD patients in western countries. As a result, their findings cannot be applied to CD patients of other nations. Because those countries' health-care structures, as well as their cultural traits and CD-coping mechanisms, differ from other regions (12, 13). Studies have shown that the prevalence and incidence of inflammatory bowel disease (IBD) in Iran, especially in the last two decades has increased significantly (14, 15). According to our best knowledge, no study assessing the HRQoL of CD patients has been undertaken in Iran. As a result, the purpose of this study was to assess the HRQoL in patients with moderate to severe CD who are using IFX or ADA and relationship between socioeconomic variables and patients' HRQoL in Iran. Furthermore, the utility scores of patients' health status can be retrieved and employed in economic evaluation studies utilizing the tool (EQ-5D) used in this study.

In total, 254 CD patients were contacted and 222 individuals agreed to participate in the study. Table 1 summarizes the demographic and clinical features of the patients. The Mean ± SD age and disease duration of the patients was 34.67 ± 12.01 and 7.318 ± 5.04 years, respectively. According to the results, more than half of the participants were male (53.6%), married (59.9%) and urbanite (73.3%). Also, 35.6% of patients were employed and 49.1% of them had university education. Moreover, 13.9% of patients had a history of surgery in the past year. Of the 222 patients, 83 patients were taking IFX, and 139 patients were taking adalimumab.

The purpose of this study was to assess the HRQoL of CD patients, as well as the factors influencing their HRQoL using general tools EQ-5D 3L and EQ-VAS, as well as the specific IBDQ-9. We used EQ-5D-3L for two reasons, first using the EQ-5D-3L instrument able us to convert the utility scores into QALY for use in economic evaluations of new medications. Second the shorter completion time in contrast to other generic instruments. Moreover, the IBDQ-9 is the most common tool for measuring HRQoL in IBD patients. It is a responsive questionnaire and brisk reflection of HRQoL changes. This is, to the best of our knowledge, the first time this study has been undertaken in Iran. According to the findings of our study, the mean EQ-5D Index of all CD patients was 0.70 ± 0.20. According to a survey of the literature, the mean score of this test in CD patients in Spain was 0.76 ± 0.18 (23), and the median (interquartile range) score of this measure in another study (24) was 0.816 (0.754–0.914). Differences in the value set produced by each country (due to differences in the type of calculation method and demographic characteristics), as well as differences in age and gender composition, level of education, factors related to health care systems, income, and study design, may explain differences in EQ-5D Index scores across studies. In Iran, the mean EQ-5D index for type 2 diabetes was 0.64 (SD, 0.27) (25), thalassemia major was 0.86 (95% CI: 0.83–0.89) (26), ulcerative colitis 0.67 (SD, 0.16) (27), psoriasis was 0.62 (SD, 0.37) (28), and colorectal cancer was 0.45 (SD, 0.03) (29). All CD patients had an average EQ-VAS score of 62.20 (SD, 19.87). Other studies found mean scores of this instrument of 66.8 (SD, 19.2) and median (interquartile range) 60.5 (50–85) (24, 25). Many factors, including cultural, economic, and social differences, might influence a person's perception and feeling in a given scenario. Our findings also revealed that the mean EQ-5D Index and EQ-VAS score of CD patients in this study was significantly lower than the mean score of Iran's general population (Supplementary Table 1). In other countries, the results were similar (30–32). In our study, the average IBDQ-9 score of all patients was 39.14 (SD, 11.46). In one study, the median (interquartile range) score of this instrument in IBD patients receiving standard care was 38.50 (33.25–46.75), in standard care with in-person visits technique was 42.00 (33.75–47.50), and in nurse-assisted telephone care method was 37.50 (28.75–46.25) (25).

According to the findings of our study, the mean EQ-5D Index of patients using IFX and ADA was 0.69 and 0.71, respectively, with no statistically or clinically significant differences between them. The EQ-VAS and IBD-9 instruments were also used in this study, however we found no statistically or clinically significant differences between patients on ADA and IFX. However, there was a significant difference between the two groups in two of the five EQ-5D health dimensions. The percentages of reported “relatively or extreme problems” in the SC dimension when taking IFX and ADA were 24.1% and 9.4%, respectively, and 54.2% and 68.3% in the A/D dimension, which were substantially different in both dimensions. A study of the literature revealed that prior trials evaluating the efficacy of ADA and IFX in Crohn's patients mainly assessed the medications' clinical efficacy (33–38). Other studies have investigated the efficacy of biological medications to non-biologic drugs in people with Crohn's disease or IBD (39, 40).

Using multivariate linear regression analysis, we explored the factors influencing HRQoL in CD patients. Our findings revealed that job factors and “having chronic conditions” had a substantial impact on HRQoL. When compared to unemployed individuals, employed patients had the best HRQoL status. Thus, they had 0.21, 19.61, and 12.26% higher mean scores than unemployed patients on the EQ-5D Index, EQ-VAS, and IBDQ-9, respectively. Several studies have validated our findings (41–45). However, Habibi et al. discovered no statistically significant link between IBDQ-32 score and job status (46). Most people's life revolves around their jobs. Individuals' financial (income stability, social safety) and social (self-esteem and identity, social contacts) requirements are met by the job. People with higher incomes have fewer concerns about these items and, as a result, are likely to have higher utility levels. We also discovered that CD patients who also had “other chronic conditions” had a lower quality of life than CD patients who did not have “other chronic diseases”. As a result, patients with the EQ-5D Index (−0.15%), IBDQ-9 (−5.84%), and EQ-VAS (−11.06%) had lower mean scores than patients without additional chronic conditions. Pizzi et al. (47) also demonstrated that chronic disorders, particularly cardiovascular disease and arthritis, had the most negative influence on HRQoL in IBD patients. Monitoring and treating other chronic conditions in CD patients can have a major impact on HRQoL promotion. As a result, in addition to monitoring and managing CD, health authorities must devise and implement particular operational plans to manage and monitor other chronic diseases that affect CD patients.

Using multivariate logistic regression analysis, we investigated the factors influencing each of the EQ-5D health dimensions. The findings revealed that employment and having “other chronic conditions” had a significant effect on four (MO, UA, P/D, and P/D) and two (MO/UA) of the EQ-5D health dimensions, respectively. Our findings revealed that many variables had a substantial effect on the A/D dimension. We discovered that the likelihood of reporting “relatively or extreme problems” in the A/D dimension is much lower in employed patients than in other individuals. Previous research has confirmed our findings (48, 49). We found that patients who consumed alcohol were five times more likely than those who did not to report “relatively or extreme problems”with the A/D dimension. Other studies agreed with us (50). Our findings revealed that smokers were less likely than non-smokers to report A/D issues. While Magalhães et al. (39) found no significant link between smoking and HRQoL in IBD patients, Severs et al. (51) found a substantial negative link between smoking and HRQoL. More research is needed to validate or refute prior findings. Finally, our study found that patients using ADA were 2.29 times more likely than patients taking IFX to report “relatively or extreme problems” in the A/D dimension. Additional research is needed to develop more proof of the influence of these medications on various aspects of patients' health, particularly the A/D component.

There are several strengths and limitations of our study that merit consideration in interpreting results. This study was the first to evaluate the effectiveness of biologic drugs (IFX and ADA) in the treatment of DC in Iran. At the same time, we used general and specific tools to measure patients' HRQoL. All study participants were patients who did not respond to conventional treatments (anti-inflammatory drugs, steroid medications and antibiotics) and had received one of the biological drugs (ADA or IFX) according to the specialist physician's prescription. Participants in this research included patients who had previously been exposed to biological drugs or patients who were using biological medications for the first time. Therefore, bias may have arisen in the conclusion of our research. We only evaluated the HRQoL of the patients who had used IFX and ADA for 1 year, and we did not evaluate the health outcomes of those who changed their drug during the year due to nonresponse to the medication, as well as those who were excluded from the study for other reasons.

This study gives EQ-5D index score estimates that can be used in health economics evaluations. The A/D and P/D dimensions are where we see the greatest reports of “relatively or extreme problems”. Psychological counseling programs, in addition to medical measures, appear to be necessary for improving patients' health. Patients who were unemployed, malnourished, or had “other chronic conditions” had much higher “relatively or extreme problems” in most dimensions of health, whereas patients who had a university education had significantly less “relatively or extreme problems” in most dimensions of health. Even after adjusting for all other variables, unemployed patients and patients with “other chronic conditions” in patients with moderate to severe CD on use of IFX or ADA had lower HRQoL than other patients. As a result, we believe that health care practitioners should be aware of not only their patients' clinical parameters, but also of their patients' “other chronic diseases,” job situation and nutritional behavior. Finally, we found no statistically significant difference in the EQ-5D Index, EQ-VAS, and IBDQ-9 scores between patients using ADA and IFX. However, there were a statistically significant difference in the SC and A/D dimensions between patients using ADA and IFX. We highly advise undertaking a cost-effectiveness study from the standpoint of the Iranian community, in which both the outcomes and expenses are examined concurrently.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Iran University of Medical Sciences Ethical Committee. The patients/participants provided their written informed consent to participate in this study.

HK, FE, KB, AR, SG, and MS conceived the experiments. HK and MS performed the experiments. MT and HK analyzed the data. All authors contributed to the article and approved the submitted version.