Over the last 20 years, biologic disease modifying antirheumatic drugs (bDMARDs) have been a cornerstone in the treatment of ankylosing spondylitis (AS) and other autoimmune diseases; however, as these agents are used for long-term treatment, clinicians are seeing the development of secondary failure in their patients.1 The reasons behind which patients respond well to treatment and which patients subsequently fail, sometimes years later, are poorly understood.1
A study by Hedley Griffiths and colleagues recently published in The Journal of Rheumatology used the “Optimising Patient outcomes in Australian rheumatoLogy” (OPAL) dataset to investigate the persistence of bDMARD treatment in population of over 5,000 patients with AS.1 The limbic asked A/Prof. Philip Robinson, Senior Staff Specialist at the Royal Brisbane Hospital and Associate Professor at the Faculty of Medicine, University of Queensland, for his opinion on the new data and the potential impact of the findings on his treatment choices in AS.
A/Prof. Robinson explained that there is currently a “quagmire of factors” that go into selecting a treatment for AS patients: “Generally, I consider factors such as extra-articular features like uveitis, skin psoriasis and inflammatory bowel disease, then decide which agents are the best for the particular scenario, then I’ll move on to other factors, like dosing route, frequency, convenience, ease of access, and whether they’ve got a streamlined authority or a patient support programme,” he said.
The value of real-world evidence
Randomised controlled trials (RCTs) or systematic reviews of multiple, homogenous RCTs, are considered the gold-standard of evidence-based medicine. However, real-world evidence (RWE) studies are an emerging trend in the medical literature, particularly in rheumatology,2 and may provide insights into the long-term outcomes of treatment. Evidence gathered in this way could help us understand different patient populations, drug prescribing patterns, patient adherence and cost-effectiveness of therapy,2,3 and may even help to ensure that clinical guidelines are harmonious with routine practice settings.3 Real-world “persistence with treatment” studies may be particularly useful, as persistence has been considered a proxy marker for both safety and efficacy, as well as patient satisfaction.2
First-line bDMARDs showed longer persistence than later lines of therapy
The OPAL dataset collects information from individual clinicians’ servers captured during routine clinical consultations in 43 rheumatology clinics around Australia. The retrospective, non-interventional cohort study by Griffiths and colleagues analysed OPAL data from patients with AS. There were 5,048 eligible patients with AS in the data set, of which 2,597 had been initiated on a bDMARD during the sampling time.
It was found that bDMARD treatment resulted in a significant reduction in disease activity in first-, second- and third-line treatment (p<0.001, p<0.001 and p<0.05, respectively), as measured as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4.0.1
Patients remained on their first bDMARD longer than subsequent agents: for first-line bDMARDs, the median persistence was not reached by Month 36 but later found to be 96 months (95% CI, 85 to 109 months). This persistence on treatment progressively declined with second- and third-line bDMARDs, to 19 months (95% CI, 16 to 22) and 15 months (95% CI, 11 to 18), respectively, when followed out to 150 months post-index.1
Longest persistence found with golimumab in all lines of therapy1
Persistence differed according to the agent used.1 Patients on golimumab had longer median persistence when used first-line, compared to adalimumab, infliximab, etanercept, secukinumab and ‘other’ treatments (which included certolizumab, tofacitinib, abatacept, rituximab, tocilizumab and ustekinumab). Patients on etanercept and ‘other’ treatments had the lowest persistence. This trend in persistence continued out to 150 months, with golimumab displaying the longest median persistence and etanercept and ‘other’ treatments demonstrating the lowest persistence.1
A/Prof. Robinson considered that these findings are in line with what he sees in his practice, although noted that retrospective findings should be interpreted with caution. “Golimumab works well, it’s got great dosing frequency, patients like it, it has a good injection device. It’s a great ‘all-round’ drug that’s dependable, so from that point of view it’s not surprising that it leads to persistence [in treatment],” he said.
Persistence reflects a range of factors, including appropriate choice of patient for therapy
A/Prof. Robinson said that choosing the right patients for golimumab helps achieve good persistence. “There are biological factors and there are what I would call patient psychosocial factors [that affect persistence rates]”, he said. “I’m going to select a patient population to put on this drug that are going to do well on this drug” he explained.
The persistence of bDMARDs varies widely in the literature. A number of publications support the findings of longer persistence of golimumab and shorter with etanercept,1,2,4,5 but other studies have found no difference between agents.6 Griffiths and colleagues explain this inconsistency in the data as being a result of the complex nature of drug persistence, which reflects multiple factors such as tolerability, patient preference, prescribing limitations, patient and disease characteristics, and efficacy.
A/Prof. Robinson said the findings reinforce that the right patients are being selected for treatment with golimumab. “What would I take from this study back to my clinical practice? Would it tell me that the decisions I’m making to put my patients on golimumab are the correct ones? You choose a certain drug because you think patients will do well on it – for a whole variety of reasons. This means that channelling bias affects the results of these studies and makes them difficult to interpret,” he said.
A/Prof. Robinson was eager to point out that although he would consider his practice to be in-line with the majority of the clinicians linked into the OPAL database, he doesn’t have insights into how clinicians choose a particular bDMARD for an individual patient. “Are their [the OPAL clinicians] reasons for differentiating between different treatments the same as mine? Possibly. Probably,” he said. “But the complex interaction between the patient and clinician and the myriad of factors that are considered means it’s really difficult to be sure”.
This article was sponsored by Janssen. Any views expressed in the article are those of the expert alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the SIMPONI (golimumab) product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.
- Griffiths H, et al. J Rheumatol 2021 Aug 1;jrheum.201551.
- Svedbom A, et al. Pt Pref Adher 2017;11:719–729.
- Acar M, et al. Open Access Rheumatol Res Rev 2018;10:151–60.