Treat to Target in axSpA

Dr. Ogdie

PHILADELPHIA—Treat to target (T2T) is a common phrase in rheumatology these days—and a welcome one.¹ Many of us are familiar with what T2T means in rheumatoid arthritis (RA), but we may be less sure of its meaning in axial spondyloarthritis (axSpA).

At ACR Convergence 2022, Alexis Ogdie, MD, associate professor of medicine and epidemiology, University of Pennsylvania, Philadelphia, shared valuable insight into what T2T currently means, and should mean, in axSpA.

Tight Control in SpA (TICOSpA)

Much work has been done to define a T2T approach in axSpA within the last few years, results of which have been incorporated into the updated 2022 ASAS-EULAR Treatment Recommendations for axSpA.²  Vital to these recommendations were data from TICOSpA, a prospective, cluster-randomized, open controlled trial examining a tight control, T2T approach compared with usual care.³ Usual care involved visits to assess study outcomes every 12 weeks, but all treatment decisions, including frequency of follow-up, were left to the investigator’s discretion.

The study included an equal mix of patients with non-radiographic axSpA (nr-axSpA) and radiographic axSpA, as well as men and women. All were naive to biologic therapy and had received non-optimal treatment by non-steroidal anti-inflammatory drugs (NSAIDs). In the T2T arm, patients came in every four weeks, and therapies were adjusted to target an Ankylosing Spondylitis Disease Assessment Score with C-reactive protein (ASDAS-CRP) of less than 2.1 (low disease activity or remission).

“There was no significant difference in the primary outcome, which was a quality of life-related patient-reported outcome, but there was a difference in disease activity [as measured by ASDAS-CRP],” said Dr. Ogdie. She focused her presentation on unpacking these results.

Why Treat to Target?

“We want to treat to target not only to make the patient feel better, but to improve long-term outcomes,” said Dr. Ogdie. “It’s interesting that in RA and psoriatic arthritis (PsA), we’ve seen several studies in which we improve disease activity levels with T2T, but don’t necessarily impact radiographic progression. And T2T has costs in terms of potential adverse events and treatment burden.”

Assessing impact on long-term outcomes is more complicated in axSpA than in rheumatoid arthritis and psoriatic arthritis because radiographic changes occur more slowly. And in nr-axSpA, patients don’t have significant radiographic disease, and many won’t ever. In the PROOF study, only about 16% of patients with nr-axSpA progressed to radiographic axSpA within five years.⁴

What’s the Target?

ASAS-EULAR recommends targeting low disease activity or remission, as defined by the ASDAS-CRP—and as used in TICOSpA—to T2T in axSpA.² “This is fairly easy to implement in clinical practice, but most of us don’t have a CRP level available to us in the clinic when we need to make a treatment decision,” Dr. Ogdie noted.

ASAS-EULAR took special care to note that the ASDAS-CRP cannot be relied upon alone and must be interpreted in the context of various “contextual factors.”²

Contextual Factors

Several contextual factors help explain why some patients respond better to treatment than others, and some have persistently higher disease activity scores. For example, studies show that depression affects response to therapy with tumor necrosis factor inhibitors (TNFi’s).⁵ Dr. Ogdie continued, “Co-morbidities also impact how a patient feels, and they’re associated with worse [disease activity scores] and even higher CRP levels.”⁶

Further, we need to consider non-inflammatory sources of pain. For example, mechanical back pain and central sensitization can play a role. Dr. Ogdie explained, “About 11 to 30% of axSpA patients have centralized pain, depending on which study you look at. These patients are very uncomfortable and don’t always fit the fibromyalgia phenotype we typically think about. Sometimes it’s widespread pain. If our target is quality of life, we must help our patients understand the difference between inflammatory disease activity and centralized pain, and address sleep, biomechanics, stress and fatigue, too.”

What’s a Better Target?

Dr. Ogdie concluded her talk with thoughts on how to develop a better T2T strategy, posing the question, “Maybe it’s not the target, but our general approach to axSpA that’s the problem. I think we should move to a whole-patient approach whereby axSpA is only a piece.” Dr. Ogdie contended that one of the best outcomes is quality of life, and the ASDAS-CRP doesn’t fully capture that.

Dr. Ogdie shared her vision of what a whole-patient approach for axSpA could look like. It would include the management of:

1. Musculoskeletal disease;
2. Uveitis, psoriasis and inflammatory bowel disease;
3. Co-morbidities;
4. Pain, fatigue and sleep;
5.  Work life (e.g., occupational therapy);
6. Family and social roles (e.g., health coaches or therapists to help adjust to daily life in the setting of a new health condition);
7. Physical activity (e.g., PT and exercise);
8. Emotional wellbeing (eg. primary care, psychiatry or psychology to address depression and anxiety); and
9. Treatment burden (e.g., pharmacy to help think about the impact of therapies on the patient).

“That’s a lot of things to do in a visit,” Dr. Ogdie concluded. “And we have a limited amount of time with patients in the room and a limited number of clinic slots. I recognize there are barriers, especially since in the U.S. healthcare system you need a visit to bill, but this is where we need to go in the future.”

Dr. Shapiro

Samantha C. Shapiro, MD, is the executive editor of Harrison’s Principles of Internal Medicine. As a clinician educator, she practices telerheumatology and writes for both medical and lay audiences.

References

1. Smolen JS, Schöls M, Braun J, et al. Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force. Ann Rheum Dis. 2018 Jan;77(1).
2. Ramiro S, Nikiphorou E, Sepriano A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2022 Oct 21:ard-2022-223296.
3. Molto A, López-Medina C, van den Bosch FE, et al. Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: Results of the open-label, pragmatic, cluster-randomised TICOSPA trial. Ann Rheum Dis. 2021 Nov;80(11):1436–1444.
4. Poddubnyy D, Sieper J, Akar S, et al. Characteristics of patients with axial spondyloarthritis by geographic regions: PROOF multicountry observational study baseline results. Rheumatology (Oxford). 2022 Aug 3;61(8):3299–3308.
5. Zhao SS, Jones GT, Hughes DM, et al. Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis. Rheumatology (Oxford). 2021 Dec 1;60(12):5734–5742.
6. Fitzgerald G, Gallagher P, O’Shea F. Multimorbidity is common in axial spondyloarthropathy and is associated with worse disease outcomes: Results from the ASRI cohort. J Rheumatol. 2019 May;jrheum.181415