Applying the Arabic Version of CQR-5 on SpA Patients Following in Two Hospitals in Riyadh, Saudi Arabia

Bedaiwi M¹, Meshikhes M^2*, Albihani A², Omair MA¹, Almalaq HM³, Alqurtas E⁴, Alhamzi H⁴, Nori R⁴, Alzahrani K⁴ and Makkawy M⁴

^*Correspondence: Meshikhes M, Saudi Council for Health Specialities, Adult Rheumatology Fellowship Program, Saudi Arabia, Email:

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Introduction

Achieving a remission or minimal disease activity when managing rheumatological disease is the clinician's goal when prescribing different modalities of treatment. Spondyloarthritis (SpA) is a heterogenous inflammatory disease with global prevalence estimated to be between 9 and 30 per 10,000 [1]. Treatment of SpA includes the use of non-steroidal anti-inflammatory drugs (NSAIDs), tumor necrosis factor inhibitor (TNFi), IL17 inhibitors, Jak inhibitors and conventional synthetic Anti- Rheumatic Drugs (csARD) [2]. Treatment adherence is essential to halt disease progression, improve signs and symptoms, and improve patient’s quality of life while obtaining the optimal response from these modalities. Therefore, it is essential to evaluate patient’s adherence to their medications as frequently as possible during clinical visits.

Evaluation of adherence to medication is a challenging procedure in clinical practice as it could not be ascertained fully that the patient is taking the prescribed drugs. In such scenario, self-report is the most commonly used method. Nonetheless, this is both challenging and unreliable as it depends on recall and varied interview techniques [3]. A more reliable measure is the use of questionnaires such as the Compliance-Questionnaire in Rheumatic disease (CQR) which is a valid, reliable self-administered questionnaire used to detect low adherence to DMARDs in rheumatoid arthritis [4]. The shortened version of the CQR, the 5-item CQR, was translated and validated in Arabic (ACQR-5) [5].

The ACQR-5 is used in this study to assess the adherence of patients with axial spondyloarthritis at two hospitals in Saudi Arabia.

Methods

Study Design

Adult patients who conformed to the ASAS classification criteria for axial spondyloarthritis were included in this cross-sectional, observational investigation [6]. The ACQR-5 was used to evaluate the degree of drug adherence.

Population

Patients with confirmed axial SpA diagnosis were recruited from SpA specialized rheumatology clinic at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, and from Prince Mohammed bin Abdulaziz Hospital (PMAH) in Riyadh, Saudi Arabia, following in the rheumatology clinics

Inclusion Criteria

Patients aged more than 18 years, diagnosed with axial SpA for at least 3 months, conforming to the ASAS classification criteria for spondyloarthritis with their last clinic follow-up within the year prior to the start date of the study were included in the study. Patients should receive one of the following drugs, either orally or subcutaneously: csDMARDs, TNFi, anti-IL17, anti- IL12/23, or Jak inhibitor.

Exclusion Criteria

Patients were excluded if one or more of the inclusion criteria were not met.

Sample Size

The sample size was calculated based on a reported CQR level of 77.1 with a 5% margin of error [7]. The required sample size to assess patient adherence in SpA patients at a confidence level of 80% is 117 patients.

Recruitment and Data Collection

Consecutive patients with confirmed SpA diagnosis were recruited. Patients who were eligible were contacted by phone and were informed about the study project. If the patient was ready to be part of the study, they were asked if they wanted to fill the form independently or they need assistance for the same. If they chose the first option, the consent was taken through a google form while in the second case; verbal consent was taken over a telephonic conversation by one of the researchers. The survey includes questions about the patient’s demographics, comorbidities, disease history, medications history, the ACQR-5, and an Arabic translation of the Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis disease functional index (BASFI).

The ACQR5 is a 5-item, self-administered questionnaire used to assess adherence in axial SpA patients. The ACQR5 score runs from "Definitely don't agree" (scoring 1) to “Definitely agree” (scoring 4).

Quantitative variables and statistical analysis

Data entry

Data were coded, entered and statistical analyses were performed using SPSS version 25. Each patient was assigned a unique study number to maintain complete patient confidentiality. The Medication of participants was classified according to the British National Formulary version 78 [8]. A Data entry check was carried out by reentering 10% of the data for error rate calculation.

Data cleaning was carried out to remove invalid observations, and outliers by plotting data points, frequency tables, cross tabulation between related variables and obtaining descriptive statistics in addition, to manually checking the data, several times.

Confounding variables

The following variables were considered confounding variables: age, gender and disease duration. These confounding variables were adjusted during statistical analysis.

Descriptive statistics and correlations

Mean and standard deviation was used for normally distributed data while non-normally distributed data were summarized as median and interquartile ranges (25th and 75th percentile values). Baseline characteristics of patients with good adherence scores were compared to patients’ bad adherence scores using t test to compare means of normally distributed data or the Mann-Whitney U test for non-normally distributed data. Pearson correlation coefficient was calculated between two continuous variables in which at least one of them follows the normal distribution. Categorical variables were reported as counts and percentages and compared bychi square test, as appropriate [9].

Ethical approval and consent

Ethical approval was obtained from both the study center’s IRB with corresponding IRB number of (E- 204913). Each participant was informed about the study objectives by the researchers a consent form was signed by each participant prior to study inclusion. No patient identifiers such as name, initials, phone number or medical record number were used. The patients’ confidentiality was maintained and the personal information of any patient was not retained by the researcher.

All data were recorded and stored in a personal laptop with a secure password. Backup data of the computer database were stored on an external hard drive. The patient forms had a unique research number and data were stored in special binders accessed by the researcher only. Data will be archived and stored for a minimum of five years.

Results

One hundred thirty-six patients from KSUMC and 38 patients from PMAH were screened for eligibility. Of 136 patients, 132 fulfilled the inclusion criteria from both centers. The questionnaire was completed by 104 patients, with a 78% response rate. Female participants composed around 52% of those who responded, with a mean age of 42 (+- 11 SD). Majority of them were Saudis living in Riyadh. Smokers comprised 15.4% of the study population, and the most common comorbidities among patients were hypertension (25%), dyslipidemia (22.1%), and diabetes (20%). Table 1 summarizes the remaining baseline characteristics.

Table 1: Baseline demographical characteristics with difference between compliance groups and p value of difference using bivariate analysis.

The adherence to medication was assessed using the ACQR5 and it was found that 89.5% of the patients were adherent to their medications. Except for age, there was no statistical difference in demographic data between low compliance and high compliance group. It was observed that the former group was substantially younger than the latter group (mean age 37 years vs 44 years, P-value 0.030).

The mean duration of disease was substantially short for the low compliance than the high compliance group (3 years vs 5.5 years, P-value 0.009). There was no significant change in the BASFI (Figure 1 A), BASDAI (Figure 1B), or agent type (Tables 2 and 3).

Figure 1. A Simple Boxplot of median BASFI Score by Compliance Level (Left). B Simple Boxplot of median BASDAI Score by Compliance Level (Right).

Table 2: SpA related information with difference between compliance groups and p value of difference using bivariate analysis.

Table 3: Odds ratio of being high compliant using binary logistic regressing of important and significant characteristics and disease activity score.

A subgroup analysis of active patients vs non-active patients for disease activity was conducted using the BASDAI score (Active disease defined as BASDAI >=4). It showed a trend towards having a better ACQR-5 score and more adherence in patient with lower disease activity.

Statistically significant odds of higher compliance were observed in older patients with greater disease duration.

Discussion

We used the ACQR-5 to assess adherence in 132 axial SpA patients treated at two hospitals in Riyadh, Saudi Arabia. The higher compliance among the present study cohort was corroborated by the findings of a Spanish systemic review. The review also ascertains that SpA patients are more compliant with biological therapy than RA patients. In SpA patients, compliance is critical to obtaining low disease activity. Although no difference in BASDAI or BASFI scores was found in our study between the compliant and low-compliant groups, a recent prospective real-world study from four Middle Eastern countries found that having lower compliance is associated with a lower probability of achieving low disease activity [10]. Nevertheless, we demonstrated that the active group was more likely to be non-compliant in a subgroup analysis of active and inactive patients using the BASDAI score (Figure 2).

Figure 2. Radar chart of BASDAI items stratified by compliance level.

Factors that might affect compliance in rheumatologically disease are age, gender, comorbidities, and the type of biologic used [11]. In contrast, our study found no differences in compliance based on drugs given, gender, or comorbidities. However, older individuals were more likely to comply than younger subjects. Although the ACQR-5 has been reported to be implemented in rheumatoid arthritis patients [12], this is the first study to apply the ACQR-5 on axial SpA patients. We presented a relatively heterogeneous group by including two different hospitals in Saudi Arabia (a governmental and a university hospital). The response rate among the participants in this study was around 80%. In conclusion, the ACQR-5 is a validated Arabic questionnaire clinicians in Arabic-speaking countries should use to assess adherence in SpA patients.

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