2021 – A year in axSpA research! Part three

Happy New Year!

Hello Everyone!

Wishing you all a Happy New Year! I hope you had a lovely time over the festive period.

This is the first blog of 2022! During the course of the year, we will again provide you with research updates, plus we also hope to provide you with some bonus blogs throughout the year, just to keep you updated on all of our activities as part of Project Nightingale. We had a very successful year last year, and we hope to achieve the same this year!

Today’s blog continues with research updates for 2021- July to September. Enjoy reading!

Exploring remission concept in axial spondyloarthritis through the perception of rheumatologists using vignettes and priority ratings

Sep 2021. Aouad and colleagues. https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab711/6370975

Remission, or inactive disease, is what rheumatologists are aiming for when they treat conditions such as rheumatoid arthritis. However, a clear definition of remission is lacking for axial spondyloarthritis (axSpA).

Several attempts have been made to define remission in axSpA, but there is a lot of controversy concerning their applicability in clinical practice. This is partly due to the variability of the disease. Axial pain and morning stiffness are thought to be key in assessing remission, or inactive disease, whereas symptoms such as fatigue and peripheral pain are multifactorial and not always related to axSpA disease activity. Treatment intake (e.g. doses of nonsteroidal anti-inflammatory drugs (NSAIDs)), extra-articular manifestations (EAMs) (e.g. uveitis) or comorbidities (being diagnosed with other conditions), are all also important to take into account.

This study is about a survey conducted with rheumatologists from French private practice or hospitals to explore their perception of remission in axSpA, including the importance of key patient-reported symptoms, EAMs and treatment intake.

The first part of the survey was to rate 36 vignettes (descriptive cases of axSpA), using the question ‘do you consider this patient in remission: yes/no’. In the second part of the survey, clinicians rated which of a list of 12 items would be important to consider for remission. This list included: measures of disease activity (Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)), CRP (a marker of inflammation in the blood), NSAID use, EAMs (such as inflammatory bowel disease, acute anterior uveitis and psoriasis), and other explanations for the symptoms (e.g. fibromyalgia). The last part of the survey aimed to determine the interval of time needed for the rheumatologist to consider a patient in remission.

For the first part of the survey, 463 out of 2400 (19%) vignette evaluations were classified as remission by rheumatologists.

The results showed that axial pain and morning stiffness were the main elements used by rheumatologists in this study to define remission. These symptoms are key elements reflecting inflammation and disease activity in axSpA, and have been associated with structural progression.

Although fatigue is important for patients, it was not thought to be key for defining remission for the rheumatologists included in the survey due to difficulty in measuring fatigue. Fatigue is included in the ASAS/OMERACT core outcome domains for axSpA, which is the set of outcomes that have been deemed as mandatory to include in all clinical trials for axSpA, which highlights its importance.

For the second part of the survey, five out of the 12 items were rated by rheumatologists as high priority in the evaluation of remission: morning stiffness (75%), axial pain (68%), EAMs (75%), NSAID use (71%) and CRP (66%), whereas only 18% selected fatigue. Maintaining remission after discontinuation of NSAID therapy is also a point to consider in the view of a drug-free remission target.

Finally, for the third part of the survey, a person was considered in remission if inactive disease was present for at least 3 months for 42% of rheumatologists, at least 6 months for 36% and longer than this for 17%.

Interestingly, the results of this survey showed that using clinical measures of disease activity alone to define remission/ inactive disease would miss key items that rheumatologists rated as high priority for evaluation of remission/ inactive disease, such as NSAID intake and EAMs. The authors state that this highlights the limits of current composite scores, and reflects the importance of taking a holistic approach when evaluating axSpA, in the context of shared decision-making.

As we can see from this article, another challenge emerges in the nature of axSpA! Do you have a story to share regarding remission? It would be great to understand different perspectives in this ever-challenging disease! Please email me on ns2271@bath.ac.uk if you want to share your story, or even to share your views on this article.

Tight control and treat-to-target in axial spondyloarthritis. Where are we?

Sep 2021. Wendling and colleagues. https://www.sciencedirect.com/science/article/pii/S1297319X21001366?via%3Dihub

Following the example of rheumatoid arthritis, the concept of “Treat-to-target” (T2T) has recently been proposed for axSpA and psoriatic arthritis. T2T is based on close monitoring of disease activity and tweaking of treatment until the desired treatment outcome/goal is reached. In inflammatory arthritis such as axSpA, this goal should be defined by the absence of clinical or biological signs of significant disease activity, or clinical remission. However, as outlined above, defining remission is incredibly challenging in axSpA!

There is a lot of variation in what clinical remission and T2T mean in different parts of the world. In the collaborated Assessment of SpondyloArthritis international Society (ASAS) and European League Against Rheumatism (EULAR) (ASAS-EULAR) recommendations, the target of treatment is to improve health-related quality of life as much as possible by controlling symptoms and inflammation for spondyloarthritis. The French Society of Rheumatology (SFR), Recommendation 1 states: “the objective of management should be to achieve and maintain clinical remission or, failing that, a low level of activity”. The American recommendation does not recommend a strict T2T strategy. These differences show that there is an absence of certainty and universal attitude toward T2T in axSpA.

This week’s article by Wendling and colleagues explores the concept of T2T in axSpA, and raises the following questions:
What should be the “target” of T2T in axSpA?

What definition of remission should be used and what tool to measure remission (if any!)?

How frequently should people be followed up/ monitored?

To summarise, observational evidence has suggested that a T2T approach may be beneficial in axSpA, however further investigations are still needed. The concept of T2T is not formally validated in axSpA. Demonstrating the potential efficacy of a T2T approach in axSpA is difficult, because axSpA is different from other chronic inflammatory rheumatic diseases (in particular rheumatoid arthritis), and presentation can vary greatly from person to person. The implementation of such a strategy in axSpA needs to show that it is beneficial in newly-diagnosed and also established disease.

For axSpA, the rheumatologist must assess people with axSpA holistically, taking into account all the dimensions of the disease and the patient, in order to achieve disease control. The target for T2T will need be useful, and feasible, in both clinical practice and clinical trials.

Ixekizumab improves sleep and work productivity in patients with non-radiographic axial spondyloarthritis: results from the COAST-X trial at 52 weeks

Sep 2021. Deodhar and colleagues. https://bmcrheumatol.biomedcentral.com/articles/10.1186/s41927-021-00218-y

As some of you sadly may be aware, axial spondyloarthritis (axSpA) can negatively affect ability to sleep and work. Poor sleep contributes to fatigue, which in turn is associated with work productivity and activity impairment.

In the last blog, we looked at the introduction of the first two IL-17 inhibitors (secukinumab and ixekizumab) for people with axSpA. Currently in the UK, ixekizumab is licensed by the National Institute for Health and Care Excellence (NICE) to treat active ankylosing spondylitis (AS, the radiographic form of axial spondyloarthritis) that is not controlled well enough with conventional therapy. It is also licensed for active non-radiographic axial spondyloarthritis (nr-axSpA) that is not controlled with non-steroidal anti-inflammatory drugs (NSAIDs), where there are also signs of inflammation. This week’s article summary reports results from the COAST-X trial, describing impact of ixekizumab on sleep, work productivity, and activity impairment in patients with active nr-axSpA.

Overall, at 52-weeks, people with nr-axSpA treated with ixekizumab reported significant improvements in sleep, work productivity, and activity. These improvements were significant when compared with placebo. These findings are very positive as it has been reported that people with nr-axSpA are more likely to report poor sleep than the general population, and interestingly, people with nr-axSpA have reported worse sleep disturbance at baseline (Week 0) compared to people with r-axSpA. It has been suggested that this may be because a greater proportion of women are affected by nr-axSpA, as well as more people being diagnosed with fibromyalgia in nr-axSpA – whereby central sensitization, a phenomenon which contributes to sleep disturbance, is more common in female patients with axSpA and in patients with fibromyalgia.

Have you received, or are you receiving, ixekizumab for nr-axSpA? Would you like to share your experience of the impact on your sleep and/ or work productivity? You can email me at: ns2271@bath.ac.uk, we would love to hear from you!

Summary & Sign Off!

I hope you have enjoyed reading these summaries, and found the information useful.

If you want to share your experience of any issues related to this blog, or comment on the articles included in the blogs, please contact me on: ns2271@bath.ac.uk.

Best Wishes,

The Project Nightingale Team