Integrating Routine PsA Structural Assessments in Clinical Practice: The Time Is Now!

Structural progression in psoriatic arthritis (PsA) can have a substantial negative impact on patient outcomes and quality of life and can be complex to address in clinical practice. While there is a growing number of safe and effective agents to help reduce structural progression in PsA, clinical guidelines are generally lacking, with the exception of those offered by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).¹ [Note that updated GRAPPA recommendations are anticipated as early as April 2022.]

The end objectives of this ECHO are to (1) support increased awareness of how critical it is to routinely monitor PsA structural progression to optimize patient outcomes; and (2) to describe agents that have been proven safe and effective in the inhibition of structural progression of PsA in clinical trials.

Systemic Agents FDA-Approved for Psoriatic Arthritis
Several therapeutic classes contain agents that have indications for use in the management of PsA (Table 1). The largest class are the TNF inhibitors, which are often the first-line choice when considering biologics and have proven beneficial for the inhibition of structural progression. Trial results have shown inhibition of structural progression even in patients who do not demonstrate a complete clinical response, implying that TNF inhibitors may inhibit radiographic progression even in the presence of smoldering disease activity. The newer classes include a variety of targeted interleukin inhibitors as well as inhibitors of CTLA-4, JAK, and PDE4.²

Table 2 lists various agents not yet shown to impact PsA radiographic structural progression. 

Recent Clinical Trials of Note
The extension period of the SPIRIT-P1 trial explored the longer-term benefit of ixekizumab, measuring both Psoriasis Area and Severity Index (PASI) scores and American College of Rheumatology (ACR) response criteria. Radiographic progression was also assessed. Data are available for both 52 weeks and 156 weeks. Ixekizumab exhibited sustained benefit through 156 weeks, including low rates of radiographic progression (Table 3). At 52 weeks of treatment, 82% and 71% of patients dosed every 4 weeks or 2 weeks, respectively, demonstrated limited radiographic progression. At week 156, inhibition of radiographic progression persisted in approximately 61% of patients dosed every 2 weeks and 71% dosed every 4 weeks. Of note, statistically significant structural damage inhibition was observed by X-ray as early as 16 weeks.^3-5

The DISCOVER-2 trial investigated the effectiveness of guselkumab in PsA.⁶ Long-term efficacy data at week 100 demonstrated that reduction of arthritis signs/symptoms and extra-articular manifestations was durable through 2 years when compared with 24-week data: ACR20 response (68%–76%), ACR50 response (48%–56%), ACR70 response (30%–36%) compared with controls (33%).⁷ Mean changes in the Sharp/van der Heijde modified score for PsA from week 52 to week 100 (range 0.13–0.75) indicated that the low rates of radiographic progression observed among guselkumab-treated patients at earlier time points extended through week 100.

Notwithstanding the reduction in radiographic progression observed in DISCOVER-2, guselkumab does not have this indication. It should be noted that the every 4-week dose of guselkumab did achieve statistical significance in inhibition of radiographic progression, thus if the FDA had approved the every 4- week dose the indication would likely have been given. However, the every 8-week dose ultimately was the approved dose by the FDA, which just missed statistical significance and thus did not receive the indication. 

Guselkumab is also under evaluation in the STAR trial evaluating patients with PsA and axial disease (https://clinicaltrials.gov/ct2/show/NCT04929210).

In the SELECT-PsA 1 study, through 24 weeks, once-daily upadacitinib 15 mg and 30 mg demonstrated improvements in clinical manifestations of PsA including musculoskeletal symptoms (eg, peripheral arthritis, enthesitis, and dactylitis), psoriasis, physical function, pain, fatigue, and quality of life (QoL), as well as inhibition of radiographic progression in patients with PsA and inadequate response or intolerance to ≥1 non-biological disease-modifying antirheumatic drug (DMARD).⁸ Data from 56 weeks confirmed duration of all efficacy endpoints from 24 weeks. In addition, mean changes from baseline in radiographic endpoints were comparable with upadacitinib 15 mg and 30 mg based on linear extrapolation at week 56.⁹

Limited evidence exists to inform treatment selection for the inhibition of PsA structural progression of the spine as this endpoint has generally not been addressed in phase 3 PsA clinical trials. The MAXIMISE trial, which analyzed the efficacy of secukinumab in patients with PsA with axial skeletal involvement, is the only trial to date that has specifically assessed axial PsA. Secukinumab 300 mg and 150 mg provided significant improvement in signs and symptoms of axial disease compared with placebo in patients with PsA and axial manifestations with inadequate response to NSAIDs.¹⁰

GRAPPA Guidance in PsA
The GRAPPA guidelines provide an outline for the overall treatment approach for psoriasis and PsA and are conveniently divided into subsections for DMARD-naïve, DMARD-inadequate, and biologic-inadequate responders (Figure 1).¹

Figure 1: GRAPPA Guidelines for Managing Psoriatic Arthritis

[Note that updated GRAPPA recommendations are anticipated as early as April 2022.]

Notwithstanding GRAPPA guidance, there are currently no guidelines that specifically govern treatment selection for the inhibition of structural radiographic progression in PsA. As such, data are needed to tease out differences between the varied agents approved for PsA and their comparative impact on structural progression.

Incorporating Routine PsA Structural Evaluation into Clinical Practice
Most clinical trials have assessed structural progression using conventional radiography, which demonstrates inhibition of erosions and joint space narrowing, though advanced imaging techniques such as ultrasound and magnetic resonance imaging (MRI) have their own distinct benefits as well. While both ultrasound (often with power Doppler) and MRI demonstrate unique imaging characteristics in the visualization of PsA structural damage (see inset), their use is far less common than conventional radiography in clinical practice.

The frequency of imaging is also an important consideration in the management of PsA. Typically, baseline radiographs of the hands and feet are obtained to assess for signs of structural damage and then periodically updated at 2- to 3-year intervals. This reassessment is particularly important in patients who have ongoing active disease despite treatment. If patients are doing well clinically, with no indications that their psoriasis has progressed to PsA or their PsA has worsened, their radiographic interval may not be as frequent.

An important and, as of yet, unanswered question is if radiographic structural assessment intervals for PsA should be performed annually following the baseline assessment as opposed to the typical 2 to 3 years. It is unknown if shortening the interval between structural assessments will improve patient outcomes through earlier intervention or if shortening the routine intervals is even feasible outside of clinical trials.

With regard to measuring PsA radiographic structural progression, multiple scoring methods have been evaluated in clinical trials. From these assessments, the Sharp/van der Heijde scale has been adapted from its use with rheumatoid arthritis and is now widely used in PsA clinical trials. The scale includes measurement of bone erosion/damage, joint space narrowing, and cartilage damage for psoriatic arthritis. Nonetheless, while PsA scales measuring structural progression have proven useful in clinical trials, their use in real-world clinical practice has thus far been limted.

Strategies to Optimize Patient Outcomes
Strategies to optimize PsA-associated outcomes include early detection; appropriate therapeutic selection based on clinical and radiographic findings along with patient preferences; integration of routine monitoring via imaging and follow-up modification of the treatment plan when necessary; and appropriate interprofessional collaboration between rheumatology and dermatology colleagues. Clinicians must maintain a good grasp on data emerging from clinical trials and ensure their patients understand how their medications affect both their PsA as well as skin manifestations. An important goal is for clinicians to explain to patients that regardless of ongoing symptoms, such as occasional flares of disease or minor symptoms of pain or stiffness, many PsA medications continue to inhibit structural progression. 

Any discussion of strategies to optimize patient outcomes associated with PsA must also focus on efforts that help remediate the social determinants of health (SDoH) that impact many of our patients. SDoH result in delays for receiving a diagnosis of PsA, negatively impact initial and subsequent treatment selection(s), and complicate patient adherence to therapy—all leading to poorer outcomes.

Communication between rheumatologists and dermatologists is also critical to improving patient outcomes. Patients often visit a dermatologist prior to seeing a rheumatologist, meaning that the dermatologist’s initial choice of therapy could make a significant difference in inhibiting PsA structural progression. Dermatologists must remain aware of the recommended frequency for imaging and should seek guidance from their rheumatology colleagues when appropriate. Rheumatologists can also provide expertise when selecting the appropriate approach to therapy. Lastly, dermatologists do not typically conduct the primary read of radiographs, rheumatologists should provide dermatologists co-managing a patient with detailed descriptions of changes from the last evaluation.

Ultimately, cross-discipline collaboration is crucial to achieving the goal of inhibiting structural progression for patients with PsA. 

Conclusion
The timely evaluation and prevention of PsA structural progression is critical to improving outcomes for patients. While the paucity of head-to-head clinical trials makes therapeutic selection complex, as additional data are gathered, more clarity will emerge as to which agent is most suitable for which patient. Clinicians should remain up to date on both existing and emerging clinical trial data. Effective communication and collaboration between rheumatologists and dermatologists remains the cornerstone to achieving optimal outcomes for patients with PsA.  

References

1. Coates LC, Soriano E, Corp N, H.B. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations 2021. EULAR 2021;2021 Virtual Meeting. See also: (Rheumatology), 02-05 Jun 2021, Virtual.
2. FitzGerald O, Ogdie A, Chandran V, et al. Psoriatic arthritis. Nat Rev. Disease Primers.2021;7:59.
3. van der Heijde D, Gladman DD, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase III study (SPIRIT-P1). J Rheumatol. 2018;45(3):367-377. doi:10.3899/jrheum.170429
4. Chandran V, van der Heijde D, Fleischmann RM, et al. Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1). Rheumatol (Oxford). 2020;59(10):2774-2784. doi:10.1093/rheumatology/kez684
5. Mease PJ, van der Heijde D, Ritchin CT, et al. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naïve patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2016;0:1-9
6. McInnes IB, Rahman P, Gottlieb AB, et al. Long-term efficacy and safety of guselkumab, a monoclonal antibody specific to the p19 subunit of interleukin-23, through two years: results from a phase III, randomized, double-blind, placebo-controlled study conducted in biologic-naïve patients with active psoriatic arthritis. Arthritis Rheumatol. 2022;74(3):475-485. doi:10.1002/art.42010
7. Mease PJ, Rahman P, Gottlieb AB, et al. Guselkumab in biologic-naïve patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomized, placebo-controlled phase 3 trial. Lancet. 2020;395:1126—1136.
8. McInnes IB, Anderson JK, Magrey M, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384(13):1227-1239. doi:10.1056/NEJMoa2022516
9. McInnes IB, Kato K, Magrey M, et al. Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study. RMD Open.2021;7(3):e001838. doi:10.1136/rmdopen-2021-001838
10. Baraliakos X, Gossec L, Pournara E, et al. Secukinumab in patients with psoriatic arthritis and axial manifestations: results from the double-blind, randomized, phase 3 MAXIMISE trial. Ann Rheum Dis. 2021;80(5):582-590. doi:10.1136/annrheumdis-2020-218808