Robert Maughan, PhD: Evaluating Treatment Cessation in Patients with Takayasu Arteritis

Rheumatology Network interviewed Robert Maughan, PhD, to discuss his recent American College of Rheumatology Convergence 2022 presentation “Evaluating the Safety and Factors Associated with Treatment Cessation in Takayasu Arteritis.” Maughan, who is associated with Imperial College London, explains the findings of the exploratory analysis, the potential for predictability in the disease course, and how they may be able to reduce the incidence rates of some of the adverse effects associated with treatment.

Robert Maughan, PhD

Rheumatology Network: Why did your team decide to evaluate the safety of treatment cessation in this patient population?

Robert Maughan, PhD: In Takayasu Arteritis, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) have recently introduced guidelines for initial treatment, but there really is little or no data available to guide decisions for what happens afterwards in terms of whether treatment cessation is safe or feasible. So, we wanted to consider the full patient pathway and give patients and clinicians an idea of whether treatment cessation could eventually be a possibility down the line. At our center, which is the Imperial College London, led by my mentor, Justin Mason, who unfortunately passed away this year, it has long been recognized that there are certain patients who can enter into long-term disease quiescence and in who it is actually safe to withdraw treatment. Using the database and the cohort which we have built over the years, we wanted to formally analyze the frequency, look at the safety and analyze the factors associated with successful treatment cessation.

RN: Can you describe the findings of your study?

RM: In our cohort, we found that 29 of 107 (27%) patients who were still linked to care managed to successfully withdrawal treatment. The median duration off treatment was 3.6 years and the majority of these patients stopped treatment due to long term disease quiescence. To evaluate the safety of stopping treatment, we reviewed serial angiography, disease activity scores and blood biomarker data and found that treatment cessation was very safe in this cohort. We have not had any of these patients require treatment restart due to a relapse in their disease and in the longest case, one patient has been safely off treatment for more than 30 years.

Next, to gain a better understanding of the factors involved in treatment cessation, we did some exploratory analysis. We found that initial treatment response, treatment duration, and age at follow-up were predictors of treatment cessation. These results are important because they give us hope that the disease course in Takayasu may be predictable, at least in some cases, and that we may be able to move towards a process where we can stratify our patients more effectively.

RN: In your opinion, what is the clinical significance of these results for both patients and clinicians?

RM: In terms of the clinical significance for the patient, like I said at the start, it's important to sometimes give the patient a potential target of what might be lying ahead during their treatment pathway. These medications, especially glucocorticoids, can have significant adverse health effects when used for prolonged periods. Even the adjunctive agents, such as methotrexate and azathioprine, are associated with toxicities that require regular monitoring for safety and they pose significant issues in terms of family planning decisions which altogether can significantly impact quality of life. So, with results like ours it may be possible to eventually implement guidelines, which can reduce treatment burdens overall with more aggressive treatment tapering and cessation targets for certain patients.

For clinicians, our work highlights the importance of learning how to stratify patients with Takayasu more effectively and outlines some of the factors that should be considered when deciding whether it is safe to stop treatment. If this can be achieved, we may manage to reduce the incidence of some of the adverse effects associated with treatment. Of course, I should emphasize that patients who stop treatment should be carefully monitored for disease relapse with regular follow-up and this is something we’ve been doing at Imperial.

RN: What about moving forward? What are the next steps for your team? Do you have any plans?

RM: Yes, absolutely! We'd be very interested in looking at collaborating with other treatment centers to see if these results are more generalizable. This will help us address the potential confounding issues associated with conducting this study at a single investigative site. We would also like to canvass the opinions and attitudes of patients and clinicians alike towards treatment withdrawal. We recognize that certain patients might have significant apprehension when it comes to withdrawing their treatment due to the potential risk of relapse.

As a scientist, I also see that the implementation of a patient stratification framework to identify refractory vs easier-to-treat cases will provide an exciting opportunity to study the basic biology and immunology associated with refractory disease – which might one day lead to better treatments. This is something I’m thinking a lot about going forward.

RN: Is there anything else you’d like our audience to know?

RM: I think we’ve covered most things, but I would like to add one important note that within this population: the arterial damage done by the disease can have significant long-term effects that is not quite reversible with current approaches. A significant proportion of these patients who managed to stop treatment did have ongoing medical problems secondary to their Takayasu Arteritis. In particular, cardiovascular problems requiring attention from cardiologists were frequent. So, even though treatment cessation is a successful outcome for the rheumatologist, there is still significant disease burden within this population.

Before we wrap up, I would like to take a moment to thank my colleagues who contributed to this work, our funders at the National Institute for Health and Care Research (NIHR) UK, and, of course, the patients who are very generous with their time and their data which makes all of this possible.