Up-to-date treatment of SpA: innovation becoming standard of care

At the 2021 European Congress of Rheumatology (EULAR), Eli Lilly & Company sponsored a symposium discussing clinical decision making and new treatment options for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). The symposium included presentations from Professor Laura Gossec from the Pitie-Salpetriere Hospital and Pierre & Marie Curie University (Paris, France) and Dr Johannes Grisar from the Sanatorium Hera (Vienna, Austria). Here we provide a snapshot of their presentations, discussing how innovations in the treatment of spondyloarthritis (SpA) are becoming standard of care.

Clinical decision-making for the management of psoriatic arthritis

Professor Gossec highlighted three key components of the question ‘how to make clinical decisions’: what to aim for when treating patients with PsA; the choice of a first targeted treatment; and personalisation based on PsA profile.

Treatment goals in PsA

Treatment goals in PsA are remission or, alternatively, low disease activity (LDA).1,2 Definition of LDA is based mainly on either very low/minimal disease activity (VLDA/MDA)3,4 or the Disease Activity Index for Psoriatic Arthritis (DAPSA),5 both of which are outlined in Table 1. It’s important to note the differences in these definitions, with DAPSA oriented around the joints, including CRP and two patient outcomes, while VLDA/MDA may be considered more global, taking into account enthesitis and skin, as well as HAQ.3,5 The prevalence of remission and LDA can vary widely, depending on the definition used.6

Table 1. Options to define LDA

Components Remission LDA
VLDA/MDA3,4 ●      Tender joints (≤1)

●      Swollen joints (≤1)

●      Skin psoriasis (PASI ≤1 or BSA ≤3%)

●      Entheses (≤1)

●      Pain (≤15)

●      Patient global (≤20)

●      HAQ (≤0.5)

VLDA: 7/7 criteria MDA: 5/7 criteria
DAPSA5 ●      Tender joints

●      Swollen joints

●      Pain

●      Patient global assessment

●      CRP (mg/dL)

DAPSA remission ≤4 DAPSA LDA: 5 to ≤14


Selecting a targeted treatment option for PsA

Numerous types of disease-modifying antirheumatic drugs are available for targeted treatment of PsA, including biologic DMARDs (bDMARDs) such as TNF inhibitors, IL-17 inhibitors and IL-12/23 and IL-23 inhibitors, as well as targeted synthetic DMARDs (tsDMARDs) such as JAK inhibitors and PDE4 inhibitors (examples listed in Table 2).7–9

Table 2. Examples of bDMARDs and tsDMARDs for the treatment of PsA

TNF inhibitors7 IL-17 inhibitors7 IL-12/23 & IL-23 inhibitors7,8












JAK inhibitors7,9 PDE4 inhibitor7




What do the guidelines say?

Professor Gossec summarised the EULAR 2019 guidelines for the management of PsA, specifically the guidance on treatment choice following inadequate response to conventional synthetic DMARDs. She highlighted the three relevant recommendations, which place all bDMARDs listed in Table 2 as equal choice in patients with peripheral arthritis and an inadequate response to ≥1 csDMARD.1 More specific guidance includes patients with:1

  • A relevant skin involvement – IL-17 or IL12/23 inhibitors may be preferred
  • Inadequate response to ≥1 csDMARD and ≥1 bDMARD, or a bDMARD is not appropriate – consider a JAK inhibitor
  • Mild disease, inadequate response to ≥ csDMARD, where a bDMARD nor JAK inhibitor is appropriate – consider a PDE4 inhibitor

Selecting a bDMARD requires a closer look at the clinical trial data. As noted above, measures of treatment efficacy (remission or LDA) encompass various outcomes. Fortunately there is now data from a number of head-to-head trials against adalimumab that can help clinicians assess treatment options in relation to these outcomes.

Ixekizumab as an example – the SPIRIT-H2H trial

SPIRIT-H2H compared ixekizumab to adalimumab (patients continued background methotrexate throughout study) and used as a primary endpoint a composite of ACR50 and PASI 100 after 24 weeks of treatment.10

Results of this trial showed significantly better outcomes in both joints and skin for ixekizumab vs adalimumab (Figure 1).10 Professor Gossec noted that these data support the use of ixekizumab in patients with PsA, due to the skin involvement often experienced by this patient group.

Figure 1. Results of the SPIRIT-H2H study showing composite of ACR50 and PASI 100, PASI 100 and ACR50 vs adalimumab at Week 24.10

  NRI was used for imputation of all missing data. *p<0.05; **p<0.001.

We are now however in the era of personalised medicine. With PsA, Professor Gossec recommends awareness of comorbidities and other factors, such as pregnancy when selecting a treatment and the potential impact of different bDMARDs. For instance, ixekizumab is not recommended for use in patients with inflammatory bowel disease,11 and should be avoided in patients with this comorbidity.

Also important to consider in PsA are extra-articular manifestations such as nail changes or psoriasis. Based on data from the head-to-head trials discussed above, EULAR guidelines recommend an IL-17 inhibitor (such as ixekizumab) or an IL-12/23 inhibitor in favour of a TNF inhibitor in cases of relevant skin involvement.1 Professor Gossec advised that discerning relevant skin involvement is simple – just ask the patient.

Professor Gossec concluded that as the body of available drugs for PsA grows, more distinct aspects of PsA need to be appropriately assessed and addressed in each patient individually. Guidelines are also moving towards a more personalised treatment approach as head-to-head trials reveal more specific details about each treatment option and its place in PsA.

New treatment options for patients with axial spondyloarthritis: From clinical trials to daily practice

Professor Grisar moved on to axial spondyloarthritis (axSpA), beginning with an overview of the current ASAS-EULAR guideline recommendations to achieve best possible quality of life in axSpA. Following a rheumatologist’s diagnosis of axSpA (which must include elevated CRP and/or positive MRI and/or radiographic sacroiliitis), patients who are symptomatic should be given at least two NSAIDs over 4 weeks (up to the maximum doses).12 Those with persistently high disease activity (ASDAS ≥2.1 or BASDAI ≥4) despite conventional treatment (2 NSAIDs) can be given a biologic DMARD.12

Unmet needs in axSpA patients

Professor Grisar then juxtaposed the guidelines with unmet needs in patients with axSpA.

Only 1 in 3 patients newly initiated on a TNF inhibitor remain on therapy 2 years later, and around 40% of patients discontinue therapy without trying a second.13 The main reason given for discontinuing a TNF inhibitor or switching to another therapy is ‘lack of effect’ – an inadequate response or failure to maintain a response to treatment.14

Tackling persistence – the example of ixekizumab in the COAST clinical trial series

To answer the question of unmet need in therapy persistence in axSpA, Professor Grisar considered the COAST clinical trials of ixekizumab versus placebo in a range of patients with axSpA.15–17

COAST included patients who were bDMARD-naïve (both radiographic and non-radiographic axSpA patients) as well as radiographic axSpA patients who had experience with a TNF inhibitor.15–17 Altogether, the COAST data showed that ixekizumab in ankylosing spondylitis/radiographic-axSpA provided statistically significant improvements in ASAS40 response rate vs placebo as early as Week 1 for TNFi-experienced patients and Week 2 for bDMARD-naïve patients, with responses sustained through Week 52.15,16,18 Ixekizumab improved symptoms, functioning, quality of life and patient-reported outcomes as well as reducing objective inflammatory markers.15,16 Looking at safety, Professor Grisar noted that treatment-emergent adverse events and discontinuation rates were fairly low.18 These data support the use of ixekizumab as a potential answer to the issue of therapy persistence in these patients.

How do these data translate to daily practice?

To showcase the potential of ixekizumab to improve persistence on therapy, Professor Grisar presented a case study of a 29-year-old married mother of one and company assistant. The patient has lived with inflammatory back pain since age 25, with a few pitting lesions on some toenails. Her work involves sitting for long periods. She has tried different NSAIDs from time to time (not regularly) with no significant success. Clinical assessment showed tenderness in the SI joints and lumbar spine, with x-rays demonstrating sacroiliitis grade 3 on the left side, and grade 2 on the right. Her toenail pitting was confirmed as nail psoriasis by a dermatologist – this led to her diagnosis of ankylosing spondylitis with mild psoriasis.

Treatment was initially NSAIDs (diclofenac 150 mg/day) for two weeks, with no success. This was followed by naproxen (1 g/day) for another two weeks, also with no success. Pre-screening for selection and initiation of a bDMARD revealed that she was QuantiFERON positive, but had no evidence of tuberculosis, with no known exposure. However, as the patient had travelled several times to India, she was given tuberculostatic therapy for 5 weeks before being initiated on ixekizumab.

By her 8-week follow-up, the patient had no back pain, didn’t require NSAIDs and her nail psoriasis had improved. At 6-month follow-up, she was in full remission (Figure 2). When asked how she felt after 6 months of ixekizumab treatment she replied “my back pain almost fully disappeared”. Professor Grisar concluded by noting that ixekizumab was chosen for this patient due to the efficacy seen in all domains in the COAST trial series. The outcomes of this case study demonstrate how treatment guidelines can be used to help patients such as this progress from an inadequate response on an NSAID to full remission.

Figure 2. Case study: treatment progress of 29-year-old female patient with AS and mild psoriasis.

Pre-treatment 8-week follow-up 6-month follow-up


CRP 0.92 mg/dL



CRP 0.12 mg/dL

No back pain

No NSAIDs required

Nail psoriasis significantly improved



Full remission

No side effects

No adverse events



ACR=American College of Rheumatology; ASAS=Assessment of SpondyloArthritis International Society; ASAS-EULAR=Assessment of SpondyloArthritis International Society-European League Against Rheumatism; ASDAS=Ankylosing Spondylitis Disease Activity Score; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BSA=body surface area; CRP=C-reactive protein; csDMARD=conventional synthetic disease-modifying antirheumatic drug; DMARD=disease-modifying antirheumatic drug; HAQ=Health Assessment Questionnaire; JAK=Janus Kinase; MRI=magnetic resonance imaging; NSAID=non-steroidal anti-inflammatory; PASI=Psoriasis Area and Severity Index; TNF=tumour necrosis factor; TNFi=tumour necrosis factor inhibitor.


This article was commissioned by Eli Lilly Australia Pty Ltd. The content is independent and based on studies and the author’s opinion. The views expressed do not necessarily reflect the views of Eli Lilly. Before prescribing please review Taltz® (link) full product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.


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  8. Tremfya (guselkumab). Approved Product Information. January 2021.
  9. Rinvoq (upadacitinib) Approved Product Information. May 2021.
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