Sofia Ramiro, MD, on the ASAS Guideline for Axial Spondyloarthritis

Dr Ramiro reviews changes from the previous guidelines for the management of axial and nonradiographic axial spondyloarthritis from the ASessment in Ankylosing Spondylitis (ASAS)working group.

Sofia Ramiro, MD, PhD, is a senior researcher at the Leiden University Medical Center, Leiden, the Netherlands, and a rheumatology consultant at the Zuyderland Medical Center, Heerlen, the Netherlands.

TRANSCRIPT:

Hello, my name is Sofia Ramiro. I'm a rheumatologist from the Netherlands from Leiden University Medical Center, and it is my pleasure to share with you the update of the ASAS/EULAR recommendations for the management of Axial SPA. As one of the coconveners of these recommendations, it's my pleasure to give you a short summary of them with a focus on what has changed compared to the previous version of the recommendations from 2016.

We have a set of 5 overarching principles which are unchanged compared to the previous recommendations. Then we have 15 recommendations, and recommendations deal with the total spectrum of the disease, axial SpA including nonradiographic and radiographic axial SpA, and they deal with nonpharmacological and pharmacological management and treatment. And I would like to emphasize specifically in axial SPA, the importance of nonpharmacological treatment. I will now focus more on pharmacological treatment, but mostly because there is where we have changes compared to the previous version of the recommendations, but not because it's more important because nonpharmacological treatment is essential in axial SPA.

But as you heard, focusing on pharmacological treatment and particularly with treatment with biological and targeted synthetic DMARDs is where we have the most of the changes. And as you have heard, targeted synthetic DMARDs are also added now to their armamentarium of the treatment of axial SPA and they're also included in the recommendations, and this happens for the first time.

Before we start with dealing with specific treatment, we make criteria for the eligibility of patients for the treatment with biological or targeted synthetic DMARDs. And there we have already the first novelty. The criteria are the presence of 1 of the factors that predisposes to a higher response. Prognostic factors of response, namely elevated CRP or the presence of inflammation on MRI or the presence of radiographic sacroiliitis, together with a failure to standard treatment, namely NSAIDs, to all patients and usually at least 2 courses of NSAIDs over a period of 2 to 4 weeks.

And if patients have peripheral involvement, then typically we also use at least 1 glucocorticoid injection locally and 1 therapeutic trial with sulfasalazine. And then additionally, we identify patients who have high disease activity and here is where we have the novelty. Now for the first time, we define those patients as patients who have an ASDAS of at least 2.1. ASDAS is a disease activity score that has shown throughout the last decade clear superiority compared to the other measurement measures that we have, for example, the DASDI. And therefore we have now chosen clearly for only using the ASDAS to select patients for treatment for the eligibility of treatment with targeted biological or targeted synthetic DMARDs. That also means that we need to use DASA-ASDAS in our daily clinical practice so that we then can assess the eligibility of patients for treatment with biologicals or tsDMARDs.

So this is what concerns the eligibility of patients for treatment, and this is the first big novelty. Then continuing, if patients fulfill criteria, then they can start a TNF inhibitor, an IL-17 inhibitor or a JAK inhibitor. This is different to the previous version of the recommendations. First, because we have JAK inhibitors that have been added as a new drug class in axial SPA. The task force also felt it was important to emphasize that although the three drug classes can be started, current practice is to start with a TNF inhibitor or a IL-17 inhibitor.

The previous version of the recommendations we had that current practice was to start with a TNF inhibitor. That means we are bringing IL-17 inhibitors a little bit more to the front, and to a real first line, together with TNF inhibitors. The reason for that is that we have more experience with these drugs and throughout the last years, we have more accumulated data on safety.

On the other hand, from JAK inhibitors, we have data only from trials and it's still only for a short period in randomized control trials, which means we do not have data from observational studies and from daily clinical practice. And at the same time, we have data borrowed from RA —the ORAL surveillance trial—which shows that there should be some caution specifically with some patients, namely patients who are older than 65 years old, that have cardiovascular risk factors, or high risk for malignancies or smoke or have smoked for a long time.

And because of this, the task force decided to put them at a lower priority level compared to TNF inhibitors and IL-17 inhibitors. Another novelty of this recommendation is the use of the extra musculoskeletal manifestations in the therapeutic choice. We know that we don't have head-to-head trials in axial SPA. Well, now at ACR we heard the results of the first head-to-head trial, but it's focusing on a structural outcome. So in terms of efficacy, we do not really have double blind randomized control trial, and that means that the data that we have, we cannot really compare from different trials. But from what we can see, there does not seem to be a large difference across the compounds when we talk about actual involvement of the disease.

However, if we talk about the extra musculoskeletal manifestations, we see a different efficacy of drugs. Therefore, in patients who have recurrent uveitis or active IBD, it's the preference to give patients a monoclonal antibody against TNF, as these drugs are more efficacious in patients either with recurrent uveitis or active IBD. Also, in patients with active IBD, IL-17 inhibitors are contraindicated.

On the other hand, in patients with significant psoriasis, it's the recommendation to give preference to IL-17 inhibitors. Here again, we do not have head-to-head trials, but we could borrow data from PSA in which there is head-to-head data showing superiority of IL-17 inhibition compared to TNF inhibition in case of skin outcomes. This together forms the recommendation using extra musculoskeletal manifestations to guide treatment choices.

Then, we assess the response to treatment, which we typically assess after at least 12 weeks of treatment. And now for the first time, we also recommend to assess response solely based on the ASDAS. And in terms of use of disease activity instrument, this of course together with a positive opinion of the rheumatologist to continue treatment because the rheumatologist is benefiting it.

But as I told you before, and what concerns the eligibility of patients for the treatment with biological and targeted synthetic DMARDs, we now do the same for the assessment of response and we only use the ASDAS. Here, we are looking for an improvement in ASDAS of at least 1.1 points. And when we have response, we see a positive response to treatment and we continue treatment. However, if we do not see response, then the task force added a new recommendation, and it's a new recommendation which reflects the struggles we have in daily clinical practice. And we see the recommendation is that an absence of treatment response should prompt the re-evaluation of the diagnosis and also consider the presence of comorbidities. And why is this? Because if we see that patient is failing to treatment with a biological or targeted synthetic DMARD, which are highly efficacious drugs, then we see in daily clinical practice that often patients do not really have the diagnosis.

Axial SPA as a diagnosis is challenging, and therefore it's not strange that after a therapeutic course, if it's not working and we would expect that it would work, it's good to question ourselves and go back to debates and check why do we think that a patient has a diagnosis and are we really sure still sure about it or can we reconsider it? Sometimes it has been some years after the diagnosis has been made and knowledge and insights and have changed. So it's good to be open to this. Also, presence of comorbidities as they can influence the assessment of disease activity. And in turn also assess the response, for example, presence of osteoarthritis or fibromyalgia. These are prevalent comorbidities and they can both lead to the presence of pain and therefore lead to a higher perceived disease activity, which therefore will translate a lower response or a nonresponsive treatment. So it's good to be alert to them and take them into account in our assessment of the response to treatment.

If active axial SPA is confirmed, and if the patient has not responded to the first treatment with biological or targeted synthetic DMARDs, then the recommendation is to switch to another one, and that can be either another biological DMARD or a JAK inhibitor. Here we don't have a recommendation in terms of prioritization of drug class because we do not have much data to support one or the other choice, and therefore we think all choices can be viable.

Again, we recommend to assess a treatment response and if patients are responding to treatment and actually at a certain moment reach a state of sustained remission, then one can consider tapering the biological DMARD. We do not have yet any recommendation on tapering of JAK inhibitors, so targeted synthetic DMARDs, because there is not yet any data on that.

And this is in a nutshell, the update of the 2022 update of the other user recommendations for the management of axial SPA, and I would like to emphasize that they cover the whole treatment spectrum of axial SPA, including nonradiographic and radiographic axial SPA, and again, including nonpharmacological and pharmacological treatment.