To assess the effectiveness of a checklist for disease activity and comorbidity control in patients with axial spondyloarthritis (axSpA).
MethodA quasi-experimental retrospective multicentre pre-post intervention study was carried out in Spain between 2016 and 2022. Improvement in disease activity and comorbidity status was determined before and after the implementation of a checklist control in patients diagnosed with axSpA. Disease activity was determined by means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) levels. Comorbidity status was determined by analysing several risk factors (blood pressure, body weight, blood test, etc.). An analysis of variance with mixed models between pre and post collected values was performed. The change in therapeutic level and disease status (low activity, remission) was determined by means of the Mc-Nemar asymmetry test.
ResultsA total of 108 patients with axSpA were included in the study. After checklist implementation, a statistically significant reduction in BASDAI of 0.44 (95%CI: 0.06–0.82, p=0.023) and a significant reduction of 3.82mg/L (p=0.001) in CRP was observed. Besides, an increase in uricemia of 0.24mg/dl was found (95%CI: 1.49–6.14, p=0.001), while no other statistically significant change in comorbidities was observed.
ConclusionsThe implementation of a checklist in daily clinical practice leads to a significant improvement in the control of disease activity in patients with axSpA.
Evaluar la efectividad de una checklist para el control de la actividad de la enfermedad y las comorbilidades en pacientes con espondiloartritis axial (axSpA).
MétodosEstudio multicéntrico retrospectivo pre-post intervención en España entre 2016 y 2022. La actividad de la enfermedad se determinó mediante el BASDAI y los niveles de proteína C reactiva (PCR). El estado comórbido se determinó mediante el análisis de varios factores de riesgo (presión arterial, peso corporal, analíticas, etc.). Se realizó un análisis de varianza con modelos mixtos. El cambio en el nivel terapéutico y el estado de la enfermedad (baja actividad, remisión) se determinó mediante la prueba de Mc-Nemar.
ResultadosSe incluyeron 108 pacientes. Se observó una reducción estadísticamente significativa del BASDAI de 0,44 (p=0,023) y de la PCR de 3,82mg/L (p=0,001); y un aumento de la uricemia de 0,24mg/dl (p=0,001).
ConclusionesLa implementación de una checklist en la práctica clínica diaria conlleva una mejora significativa en el control de la enfermedad en pacientes con axSpA.
Axial spondyloarthritis (axSpA) is a chronic inflammatory musculoskeletal disease mainly affecting the axial skeleton. It frequently associates important comorbidities, especially cardiovascular diseases and risk factors.1 Since axSpA is a lifelong disease with no cure and often affects young patients, axSpA patients require regular follow-up.
National and international guidelines recommend individualized follow-up, including patient-reported outcomes (PROs), clinical findings, laboratory tests, and imaging.2,3 In daily clinical practice, however, regular visits are often not systematically performed due to time constraints and the need for specialized personnel.4 In fact, a low rate of systematic report of the recommended outcome measures has been recorded.5,6 As a result, many patients with axSpA may not receive optimal disease control, leading to suboptimal management and an increased risk of complications.5,6
In this context, checklists emerge as a simple and effective tool to ensure rigorous and standardized follow-up. These checklists allow for a more structured assessment, improve the detection of comorbidities, and optimize the control of radiographic progression and treatment response.4 The Group for the Study of Spondyloarthritis of the Spanish Society of Rheumatology (GRESSER) designed a checklist to improve the clinical evaluation and monitoring of patients with axSpA.4 Indeed, the implementation of this assessment checklist in clinical practice was feasible and led to a clear and significant improvement of the monitoring in patients with SpA.7 There is a gap in the literature on checklist implementation for axSpA. Therefore, the aim of the present study is to analyse the impact of implementing this checklist on disease activity control and comorbidity management in patients with axSpA.
Materials and methodsStudy design and participantsThis was a quasi-experimental, multicentre retrospective study conducted in patients diagnosed with axSpA, consecutively recruited from 7 Spanish hospitals. Eligible participants were adults (>18 years) diagnosed with axSpA according to the ASAS criteria8; and under follow-up in the Rheumatology department. To be included, participants needed to have a BASDAI score recorded both before and after the checklist implementation. Exclusion criteria included: patients diagnosed with fibromyalgia, depression or cognitive illness (dementia or others), or any other situation which, in the opinion of the investigator, prevented a correct assessment of BASDAI score.
The study received approval from the Ethics Committee of all the participating hospitals.
Data collectionDemographic and clinical data was collected retrospectively for each patient in standardized electronic case report forms (eCRF). Data collection was performed in two distinct periods: the pre-implementational period, from February 2016 to February 2017, and the post-implementation period, from 2020 and 2022.
Sample size calculationThe sample size was calculated assuming a type I error of 0.05 and a power of 80 To detect a 0.5-point difference in BASDAI in a hypothesis test with repeated measurements, a total of 116 patients were required.
EndpointsThe primary endpoint was to assess the change in terms of disease activity after checklist implementation by means of absolute BASDAI index (0–10). A BASDAI score>4 indicates suboptimal disease control9; low disease activity is defined as BASDAI<4 and CRP<5, and remission is defined as BASDAI≤2 and CRP<5.10 An important clinical response is defined as achieving a BASDAI 50 (50% improvement from the initial BASDAI value. The change in C-reactive protein (CRP) levels (measured in mg/l) was also determined.
The secondary endpoint was to assess changes in comorbidities, based on variables recorded in questionnaires and laboratory tests from medical records, compared to the clinical status prior to the checklist implementation.
Statistical analysisA descriptive analysis was performed of all the variables recorded for the study sample. For continuous variables, mean and standard deviation (SD) or median and interquartile range (IQR) were calculated; for categorical variables, counts (n) and percentages are presented.
To compare pre- and post-implementation scenarios, the difference in quantitative variables with their 95% confidence (95%CI) was determined using repeated measures analysis with mixed models. Besides, the change in disease activity and disease status (low activity, remission) was determined by using the Mc-Nemar asymmetry test. All statistical tests were 2-sided and were performed using a 5% significance level. Statistical analysis has been adjusted for age and sex as confounding factors. The statistical analysis was performed with the software package SPSS 20 and STATA 17.
ResultsDescription of participantsA total of 108 patients diagnosed with axSpA from 7 Spanish hospitals were included in the study. The sample was balanced between men and women (43.5% women), with a total mean age of 43.6 years (Table 1). The median disease duration was 5.4 years, and dyslipidaemia was the most frequent comorbidity (32.4%), followed by depression (23.1%) and high blood pressure (21.3%) (Table 1). Regarding treatment, 46 (42.6%) patients were on biologics, while 8 (7.4%) were not receiving any treatment (Table 1). A total of 35 patients (33%) showed low disease activity, and 21 (20%) patients showed disease remission (Table 1).
Baseline characteristics of included patients (n=108).
| n (%) | |
|---|---|
| Demographics | |
| Age (years), mean (SD) | 43.6 (11.7) |
| Sex, female | 47 (43.5%) |
| Disease characteristics | |
| Years of evolution, median (IQR) | 5.4 (2–8.4) |
| Low disease activitya | 35 (33%) |
| Remissionb | 21 (20%) |
| Comorbidities | |
| Dyslipidaemia | 35 (32.4%) |
| Depression | 25 (23.1%) |
| High blood pressure | 23 (21.3%) |
| Obesity | 22 (20.4%) |
| Osteoporosis | 11 (10.2%) |
| Diabetes | 9 (8.3%) |
| Cardiovascular event | 8 (7.4%) |
| Gout | 7 (6.5%) |
| Gastric ulcer | 6 (5.6%) |
| CKD | 5 (4.6%) |
| Treatment | |
| No treatment | 8 (7.4%) |
| NSAIDs | 78 (72.2%) |
| DMARDs | 38 (35.5%) |
| Biologics | 46 (42.6%) |
CKD: chronic kidney disease; DMARD: disease-modifying antirheumatic drugs; IQR: interquartile range; NSAID: nonsteroidal anti-inflammatory drugs; SD: standard deviation.
Disease activity was estimated using BASDAI and CRP levels before and after checklist implementation. Prior to the checklist implementation a mean BASDAI of 4.1 and a mean CRP of 7.1mg/L was estimated (Table 2). Twenty-four (24) months after checklist implementation, a significant reduction in BASDAI of 0.44 (95%CI: 0.06–0.82, p=0.023) and a significant reduction in CRP levels of 3.82mg/L (95%CI: 1.49–6.14, p=0.001) was observed. Additionally, 15% of patients (16/108, 95%CI: 10–24%) reached the BASDAI50 criteria 24 months post-implementation.
Change before/after checklist implantation.
| Before checklist implementation | After checklist implementation | Change before/after implementation | ||
|---|---|---|---|---|
| Mean (SE) | Mean (SE) | Mean (95%CI) | p-Value | |
| Disease activity assessment | ||||
| BASDAI (0–10) | 4.1 (0.2) | 3.6 (0.2) | −0.44 (−0.06, −0.82) | 0.023 |
| CRP (mg/L) | 7.1 (0.9) | 3.3 (0.9) | −3.82 (−1.49, −6.14) | 0.001 |
| Questionnaires and laboratory tests | ||||
| SBP (mmHg) | 123.9 (2.5) | 122.0 (1.5 | −1.87 (3.16, −6.91,) | 0.466 |
| DBP (mmHg) | 74.8 (1.7) | 75.2 (1.0) | 0.35 (3.58, −2.88) | 0.83 |
| Cholesterol (mg/dl) | 186.8 (3.3) | 186.5 (3.3) | −0.28 (5.54, −6.11) | 0.924 |
| LDL (mg/dl) | 115.8 (5.9) | 109.8 (4.4) | −6.05 (5.86, −17.95) | 0.32 |
| HDL (mg/dl) | 57.4 (3.1) | 59.1 (2.4) | 1.71 (7.25, −3.83) | 0.546 |
| Uricemia (mg/dl) | 4.8 (0.1) | 5.0 (0.1) | 0.24 (0.40, 0.08) | 0.003 |
| D vitamin (ng/dl) | 31.6 (1.9) | 28.4 (1.5) | −3.22 (0.53, −6.97) | 0.092 |
| Body weight (kg) | 75.1 (1.7) | 75.5 (1.5) | 0.38 (2.72, −1.97) | 0.753 |
| BMI | 26.3 (0.6) | 26.5 (0.5) | 0.20 (1.04, −0.64) | 0.642 |
BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BMI: body mass index; CI: confidence interval; CRP: C-reactive protein; DBP: diastolic blood pressure; HDL: high-density lipoproteins; LDL: low-density lipoproteins; SBP: systolic blood pressure; SE: standard error.
In bold, significant p values.
A significant change was observed in disease activity level, with 40% (28/70) of subjects showing low disease activity (p=0.001), and 19% (16/85) reaching remission (p=0.027). Regarding comorbidities, although it was observed a significant increase in uricemia of 0.24mg/dL (p=0.003), both pre- and post-implementation figures are within the normal range (Table 2). Finally, no significant change in other comorbidities was detected (Table 2).
DiscussionIn this study we evaluated the impact of implementing an assessment checklist for monitoring patients with axSpA in clinical practice. Our findings indicate that incorporating this clinical control tool into routine medical practice significantly improved disease activity monitoring in patients with axSpA. The present study fills a gap in the literature of checklist tool implementation impact on disease control in axSpA.
Controlling disease activity is the primary goal in treating patients with axSpA, as it prevents irreversible structural damage, long-term functional disability, reduced quality of life (QoL), and systemic inflammation that elevates cardiovascular risk.3 Current guidelines recommended evaluating signs and symptoms of disease activity in daily practice through BASDAI and/or the ASDAS (Ankylosing Spondylitis Disease Activity Score). However, it has been evidenced that up to 60% of the medical histories of patients with axSpA did not assess joint involvement, 87% did not have a joint index, and 84% did not evaluate a functional index.5,6 The low adherence to guidelines in axSpA monitoring has been partially explained by short visit time, and lack of motivation or knowledge.4 To address the gap between recommendations and their implementation in daily practice, it was conceived an assessment checklist.4 It is a structured tool aimed to conduct more specific axSpA monitoring, that includes evaluation of medical records, clinical findings, comorbidities, activity, function, laboratory tests and imaging in accordance with current guidelines. 2,3After two years of implementation in routine care, a significant improvement in the control of disease activity in patients with axSpA was observed. To our knowledge, this is the first study demonstrating the positive impact of using a standardized checklist in clinical practice for improving the management of patients with axSpA.
Comorbidities are common in axSpA, with the majority of patients presenting at least one comorbid medical condition.11,12 The impact of comorbidities on clinical outcomes and patient's QoL is well known: comorbidities are associated with poorer PROs, treatment response and higher mortality, as well as low work productivity.11,12 In addition, comorbidities are linked to axSpA evolution and treatment, since they influence treatment decisions and impact on treatment outcomes.11,12 Therefore, systematic screening and early detection of comorbidities in patients with axSpA is of outmost importance. Nevertheless, the emAR II study carried out in Spain evidenced that up to 51.1% of cases of SpA did not have any registered comorbidities6 and consequently, not properly managed. In the real-world management of axSpA, monitoring and managing potential comorbidities through validated tools such as the present checklist leads to a better care process that impacts on improving disease activity. Conversely, tight control of the SpA leads to a reduction in the rate of comorbidities such as cardiovascular disease.13
In the present study, it was observed a significant increase in uricemia after checklist use implementation. The observed increase may be explained by its systematic assessment and subsequent identification. Although an association between high concentration of serum uric acid and axSpA has been previously reported,14 pre- and post- checklist implementation figures were within the normal range, without risk of increasing gout incidence. Finally, after checklist implementation, no significant change in other comorbidities were detected.
Strengths and limitationsThe main strengths of the study include the design used, with high heterogeneity in participant centres (infrastructure, size, resources, etc.) that ensures representativeness at country level. This study has some limitations, mainly due to the its quasi-experimental design, with no randomization, where it cannot be ensured that the changes that appeared are due to the intervention itself, other interventions or uncontrolled factors. Randomization by patient is not feasible due to the nature of the checklist itself. Since its first use, the rheumatologist would be biased when attending a patient in a control group. Besides, there is the possibility of the Hawthorne effect, the placebo effect, regression to the mean and non-control of the natural evolution of the disease. However, to avoid these biases the before-after single group design study was applied, where each subject acting as their own control. Finally, biases related to the method of choice of centres and patients and the poor quality of medical records cannot be ruled out.
ConclusionsThis is the first checklist proved useful for disease control in daily clinical practice in patients with axSpA.
Compliance with ethical standardsThe study received approval from the Ethics Committee of all the participating hospitals.
Funding informationThis Investigator Initiated Study was financially supported by UCB Biopharma SRL.
Conflict of interestDr. M.V. reports conflict of interest with UCB. The other authors declare that they have no conflict of interest.
Data availability statementThe authors confirm that the data supporting the findings of this study are available within the article. For detailed information of data bases, you may contact Dr. Almodovar, at raquel.almodovar@salud.madrid.org.
This Investigator Initiated Study was financially supported by UCB Biopharma SRL. The authors would like to thank Alba Gomez, PhD, for providing medical writing assistance.
The followings are the supplementary data to this article:
