Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City


Wan Yu Png, BSc (Pharm)(Hons); Yu Heng Kwan, BSc (Pharm)(Hons); Yi Xuan Lee, BSc (Pharm)(Hons); Ka Keat Lim, MPharm, MSc; Eng Hui Chew, BSc (Pharm)(Hons), PhD (Pharm); Nai Lee Lui, MBBS, MMed, MRCP, FAMS; Chuen Seng Tan, BSc, MSc, PhD; Julian Thumboo, MBBS, MMed, MRCP, FAMS, FRCP; Truls Østbye, MD, MPH, MBA, PhD, FFPH; Warren Fong, MBBS, MRCP, FAMS


J Clin Rheumatol. 2019;25(2):59-64. 

In This Article


This is the first study exploring factors associated with biologics initiation across patients with different demographics, clinical status, and PRO in patients with AxSpA in an urban Asian setting. Although there are treatment algorithms in place for treatment of AxSpA,[2,16] findings from this study revealed that there were other factors associated with the initiation of biologics. We found that age, clinical status (ESR level, presence of PUD), quality of life, and lack of good response to NSAIDs were associated with biologics initiation, whereas patient's socioeconomic factors such as employment status were not.

There could be many reasons to why older age was associated with lower odds of biologics initiation. A possible reason could be the underreporting or lower perception of pain in older AxSpA patients due to the belief that pain is a normal process of aging.[17] As compared with younger patients, older patients may feel a lesser need to be on more aggressive therapeutic strategies; they may assume old age is associated with decreased level of daily activities and low probability of recovering and therefore see reduced need to receive more aggressive and expensive medications such as biologics to improve disease activity and functional capacity.[18] The inverse relationship between age and initiation of biologics found in this study could also be due to reasons not related to the high cost of biologics or patient's preference. For example, it could be due to clinicians' cautious use of biologics in older patients because of their greater vulnerability to adverse effects such as infection complications.[19]

In this study, higher ESR levels indicated an increase in the odds of biologics initiation. Indeed, studies have reported that higher levels of inflammatory markers such as ESR were associated with radiographic progression and higher disease activity.[20,21] There are studies performed on biologics etanercept and anakinra, which have reported significant improvement in inflammatory markers in AxSpA patients.[22,23] Therefore, it is recommended that clinicians should consider looking at ESR levels when making decisions to start patients on biologics. However, although ESR is an objective indicator of disease activity, it should be noted that there are several other factors that can lead to elevation of ESR such as infection, malignancy, and older age.[24] Thus, clinicians should be cautious when interpreting ESR and should correlate ESR with other clinical presentations of the disease.

Short-Form 36 Health Survey is an instrument developed by Ware,[12,25] which concerns the impact of disease from the patient's (rather than a clinical) perspective. It has been validated in countries such as the United States and Singapore; it is proven to have good reliability and validity in accessing health-related quality of life in AxSpA patients.[26,27] In this study, the MCS component of SF-36 was found to be associated with biologics initiation, with low MCS score (worse mental health state) indicating an increase in the odds of biologics initiation. In the CORPUS cohort study,[28] which looked at how quality of life (SF-36) influenced biologics initiation in RA and spondyloarthritis patients in France, it was found that quality of life was not associated with biologics initiation in patients with spondyloarthritis. This difference in findings between the CORPUS and PRESPOND study could be due to the nature of the health care system in the 2 countries. In France, biologics are reimbursed without restrictions by the National Health Insurance System, whereas in Singapore, the cost of biologics is usually borne by patients or copaid by insurance companies. Thus, in Singapore, biologics initiation may be more driven by subjective PROs. A study by Martindale et al.[29] concluded that disease status is closely linked to psychological status in AxSpA patients, as BASDAI and Bath Ankylosing Spondylitis Functional Index correlate strongly with all SF-36 domains. Bath Ankylosing Spondylitis Disease Activity Index and Functional Index have also been found to correlate significantly with anxiety and depression levels. As there are studies that report biologics treatment leads to an improvement in MCS score,[30,31] it is therefore recommended that patients should spend a few minutes to answer the SF-36 questionnaire during visits to aid clinical evaluation and management of the disease. Hence, this study has demonstrated that both objective (ESR) and subjective (SF-36) indicators of disease activity have aided clinicians in decisions to initiate biologics by providing a more holistic picture.

With regard to patient's response to NSAIDs based on clinical judgement, poor response to NSAIDs is associated with increased odds of biologics initiation in our study. This result is consistent with a consensus statement published by a task force panel composed of 11 locally recognized rheumatologists based in government-restructured and private hospitals in Singapore. The consensus statement stated that patients should have failed 2 sequential NSAIDs at maximal tolerated doses for a total duration of at least 4 weeks and should have been compliant to an ongoing, concomitant, appropriate physiotherapy and exercise program of at least 3 months' duration before biologics can be initiated.[16] Our findings suggested that patients who had PUD were 10 times more likely to be initiated on biologics. This associations between PUD and initiation of biologics have not been studied or found in other published studies. As PUD is an established adverse effect of NSAID use,[32,33] patients who develop PUD or have existing PUD are likely to discontinue NSAID use and to be initiated on biologics instead so as to prevent aggravation of PUD.[34] Hence, other than the objective and subjective indicators of disease activity, response to ongoing treatment is also an important factor to consider before initiating biologics.

This study has several limitations. First, missing data, which are a common problem across all longitudinal studies,[35] resulted in the exclusion of 25% of the available patients in this study. However, based on sensitivity analyses between included and excluded patients, we found that there was no difference in patient characteristics between those who initiated biologics and those who did not. Hence, it was deduced that no bias in the findings would have resulted from this study. Second, patients were recruited only from a tertiary institution in Singapore, which could limit generalizability to patients in other settings. However, as the study was conducted in the center, which is the largest out of the 3 local centers managing AxSpA in Singapore, patients included were likely representative of the population.

In conclusion, age, ESR, MCS of SF-36, presence of PUD, and lack of good response to NSAIDs were found to be associated with biologics initiation in patients with AxSpA in Singapore. Clinicians should recognize these factors so as to optimize therapy to achieve more effective disease management and improvement of treatment outcome for AxSpA patients.