2021 – A year in axSpA research! Part two

Last blog of this year!

Hello Readers!

What an interesting year it has been, and thank you for bearing with us as we resumed our research update blogs!

This year we have seen a manuscript published that reports some of our first results from the Project Nightingale dataset on flares in axial spondyloarthritis (axSpA), a new addition to the Project Nightingale team, the launch of the Act on Axial SpA campaign which is aimed at reducing the current average time of 8.5 years to diagnosis, lots of National Axial Spondyloarthritis Society (NASS) Facebook lives, and just recently we have had a research poster accepted at the British Society for Rheumatology Conference (this is based on the research I’ve been working on)!

Today’s blog continues with research updates for 2021- April to June. The first article summary is related to the project that I’ve been working on since starting my role in April 2021- the use of telemedicine in inflammatory arthritis. You may remember in my first blog, I mentioned that we are exploring virtual/ remote ways that rehabilitation has been provided to people with rheumatic and musculoskeletal disease over the past 10 years, and particularly since Covid-19. Broadly speaking, telemedicine is the diagnosis and treatment of patients remotely using digital telecommunications technology (although different terms are used in the literature such as telerehabilitation and telehealth). This type of remote care has increased hugely since Covid-19. The first article looks at the impact it has had in Italy.

Use of telemedicine during the COVID 19 pandemic in patients with inflammatory arthritis: a retrospective study on feasibility and impact on patient reported outcomes in a real life setting

May 2021. Chevallard et al 2021. https://link.springer.com/article/10.1007%2Fs00296-021-04863-x

This study is based on data collected during the first lockdown that happened between March 1 2020 to May 31 2020 in Italy. The participants included people who live with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS/ radiographic axSpA, r-axSpA). People receiving biologic disease-modifying anti-rheumatic drugs, or bDMARDs, subcutaneously (that is under the fatty layer of skin, for example in the tummy) or targeted synthetic DMARDs or tsDMARDs orally (through the mouth) were followed remotely. In Italy, these patients are required to receive their medication every two months. Results are presented before and after this 3-month lockdown period of the COVID-19 pandemic.

During the study, a rheumatologist called the study participants and asked them about any signs of disease activity, side effects related to therapy, comorbid pathologies (where multiple conditions are diagnosed), and COVID-19-related symptoms that might require the need for an outpatient rheumatological visit. The participants also entered data on Patient-Reported Outcome measures (PROs) which is data collected on the person’s health using tailored questions. In this study, generic PROs on general health (GH), pain, and fatigue were included, as well as AS/ r-axSpA disease-specific PROs such as Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Bath AS Global Index (BASGI) – which you are probably familiar with filling out in clinic. This data was entered electronically using an app and was also monitored by the rheumatologist. If there were no issues, the outpatient appointment was postponed for two months. If any of the study participants had developed a disease flare, side effect, or telephone management was considered inadequate, an urgent outpatient re-evaluation was scheduled. The PRO data was completed before the lockdown (between 1st January 2020 and 1st March 2020) and after the lockdown (between 1st June 2020 and 1st August 2020).

A total of 341 patients with RA (137), PsA (85), or AS/r-axSpA (59) had a clinical evaluation or assessment by telephone interview, and also completed PRO data. 70% (449 visits) of in-person scheduled visits were postponed, with evaluations deemed sufficient via telephone, along with completing PROs electronically, and delivering drugs directly to study participants. For 193 telephone evaluations, it was deemed better to evaluate study participants with a standard outpatient visit and the drug was given at the hospital. Comparisons were made between those people that had at least 1 visit in person and those that received telemedicine alone. In addition, results were compared before and after the 3-month lockdown. There were no GH or pain differences before and after lockdown in any of the conditions, or by method of receiving care.

Although this study was only for a 3-month period, it shows that receiving care by telemedicine can be successful when combined with: a flexible approach (seeing a rheumatologist when necessary), the use of an app to measure PRO data, and the ability to deliver drugs directly to patients. It is important to note that telemedicine is best suited for people who have an established diagnosis (compared to newly diagnosed) and have stable disease. Telemedicine may not be the best option for those with a disease flare or if they have complexity of their disease which makes following-up remotely difficult.

Telephone consultations were chosen because of the need for a quick solution when lockdown began, but consultations could also take place by video calls. As mentioned above, in our latest research we are exploring ways that telemedicine can be used in rheumatic and musculoskeletal diseases. We hope to be able to report on aspects of telemedicine such as type of technology used, how long the study lasted, what data was collected during the study, amount of interaction with a healthcare professional, and so on. The results of this study will be reported around spring time next year, so watch this space!

If your routine or usual care has, or was, changed to being remote or virtual as a result of Covid-19, and you would like to share your story, feel free to email me on: ns2271@bath.ac.uk

Influence of smoking and obesity on treatment response in patients with axial spondyloarthritis: a systematic literature review

May 2021. Prada and colleagues. https://link.springer.com/article/10.1007%2Fs10067-020-05319-6

In a previous blog, we saw that some potential predictors of response to treatment with biologic disease-modifying anti-rheumatic drug (bDMARDs) in axial spondyloarthritis (axSpA) had been identified. In the article summary the authors mentioned that obesity and smoking are associated with not responding well to treatment. This current article looks at a review of literature on this topic- which means that research published on this topic is systematically searched for, and relevant information on the study, is extracted. As a review covers more than one study’s findings, it can be a more reliable and representative way of reporting findings. The literature that was searched in this study was performed in biomedical databases dating back as far as 1950.

Treatment for axSpA includes intensive treatments such as biological therapies based on tumour necrosis factor (TNF) alpha inhibitors, and on interleukin 17 (IL-17) inhibitors. These therapies have entirely changed the outcome of the disease, greatly improving the quality of life of patients with axSpA. Although these treatments can be very successful, not all patients have a good clinical response or treatment success. Data from clinical trials and observational studies show that as many as 50% to 65% of patients with axSpA do not have a satisfactory clinical response to their first biologic therapy. Smoking and obesity are identified as modifiable factors potentially influencing treatment response.

After searching the literature, 12 studies were identified as being relevant: six on obesity, and six on smoking. Of all the studies found, the only treatment included was anti-TNF therapy. For the obesity studies, a total of 1333 patients were included. BMI (Body Mass Index) is a measure that uses your height and weight to work out if your weight is healthy. Of these, 609 (45.6%) had a BMI of less than or equal to 25 kg/m2 (normal weight); 501 (37.5%) had a BMI between 25 and 30 kg/ m2 (overweight); and 194 (14.5%) with a BMI more than 30 kg/m2 (obese). Five out of the six studies observed a negative influence of obesity on treatment response (i.e., the response to therapy was worse in people who were obese). For the smoking studies, a total of 3917 patients were included: 1410 (35.9%) smokers, 979 (24.9%) ex-smokers, and 1513 (38.6%) non-smokers. Only two studies out of the six found a negative influence of smoking in response to TNF therapy. Results were identified by checking the reasons for discontinuation of the therapy, or in changes in health-related quality of life.

The negative relationship between obesity and response to therapy is due to the impact obesity has on inflammation in the body which increases the risk of poorer response, as well as changing the pharmacokinetics (the movement of drugs within the body) of anti-TNF agents and other biologics. The findings from the smoking studies are inconclusive as there are only two studies that found this negative influence with treatment response. More research would be needed to establish if there is a link between smoking and not responding well to treatment. Another important note is that these studies only relate to the treatment response of anti-TNF therapy, not anti-IL-17 agents, nonsteroidal anti-inflammatory drugs (NSAIDs), or manual therapies.

Below are some useful resources from the National Axial Spondyloarthritis Society (NASS) website on diet and smoking, including help to stop smoking on the NHS website:




Have you had a low treatment response based on the factors identified in this study? Would you like to share your experience? If so, feel free to email me on ns2271@bath.ac.uk

Anti-IL-17 Agents in the Treatment of Axial Spondyloarthritis

May 2021. Atzeni and colleagues. https://pubmed.ncbi.nlm.nih.gov/33977094/

The main aims of axial spondyloarthritis (axSpA) treatment are to decrease inflammation and prevent or slow structural spinal damage in order to reduce pain and stiffness, and preserve spinal mobility. The treatments for axSpA are highly effective in reducing disease signs and symptoms, improving physical function, and increasing quality of life. Although anti-interleukin 17 (IL-17) treatments such as secukinumab and ixekizumab and have been mentioned in previous blogs, including above, they have not been extensively covered in any of our article summaries. Some patients do not respond well to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy, which is usually the first type of treatment provided to people with axSpA. Also, there are some people who should not be offered NSAIDs as it is contraindicated (for example, if also have comorbid bowel problems such as IBD), and for these people biological drugs (such as tumour necrosis factor (TNF) and IL-17 inhibitors) are strongly recommended. This review article looks at the role of anti-IL-17 drugs, and how safe and effective they are for use in axSpA.

IL-17 is a pro-inflammatory cytokine, which means it acts to make disease worse, and can lead to numerous autoimmune responses or inflammatory diseases, including inflammatory arthritis. IL-17A and IL-17F are expressions of IL-17, and are both critical drivers of inflammation. Serum levels of IL-17A and IL-17F are suggested to be a lot higher in people with SpA than in healthy people, and high levels of IL-17 in people with ankylosing spondylitis (AS) or radiographic axial spondyloarthritis (r-axSpA) may suggest higher disease activity. More evidence is still needed to explore the role of IL-17F in the pathogenesis (development) of SpA, but what is known is that dual IL17A and IL-17F blockade reduces inflammation better than IL-17A blockade alone.

Results from clinical trials and real-world studies have shown that IL-17 inhibitors are safe and work effectively in axSpA. This means that the introduction of the first two IL-17 inhibitors (secukinumab and ixekizumab) has extended the treatment options for people with axSpA. There are also three other similar drugs in the development process (bimekizumab, brodalumab and netakimab). Currently no predictive factors of good response to IL-17 inhibitors are available- in other words factors to identify those people that may be most likely to react well to the treatment, and there is limited information on the biological markers or biomarkers (a measurable indicator of some biological state or condition) to predict which medication is most appropriate for individuals. However, IL-17 inhibitors have very recently been licensed and hopefully this extremely useful data will become available in the near future, as it has for biologic disease-modifying anti-rheumatic drugs (bDMARDs).

In 2016, the National Institute for Health and Care Excellence (NICE) published guidance on secukinumab for treating active AS/r-axSpA after treatment with NSAIDs or TNF-alpha inhibitors. More recently, secukinumab was licensed in the UK for treating non-radiographic axial spondyloarthritis (nr-axSpA), and in July 2021, NICE guidance was published for the use of secukinumab for treating nr-axSpA.

This is great news as secukinumab has been proven to be safe and effective, and opens up more treatment options for those that don’t respond well to NSAIDs and TNF inhibitors.

Support during Christmas Time

As last year, this year we face similar challenges with uncertainties of Covid-19.

Here are some resources and helplines that can offer support during this festive season, which were posted in last year’s blog. If you feel you need support or help during this time, please reach out to these resources.

Some of the helplines may vary over the Christmas period, however NHS 111 and the Samaritans are free and available 24/7, 365 days a year.

Summary & Sign Off!

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

If you want to share your experience of any issues related to this blog, please contact me on: ns2271@bath.ac.uk. I would love to hear from you!

We look forward to providing you with more updates in the New Year, and another exciting year for Project Nightingale (see our Home Page!).

Have a wonderful Christmas and New Year!

Best Wishes for 2022,

The Project Nightingale Team