GRAPPA 2021 Pilot Grant Award Reports

Validating feasible composite disease activity measures for use in daily clinical practice in patients with psoriatic arthritis (Fazira Kasiem, Marijn Vis, and William Tillett; 2021 awardees)

Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory disease that can lead to progressive joint destruction and deterioration of functional status. PsA can have a negative effect on health-related quality of life and the ability to work.^1,2 Numerous disease activity measures have been developed previously; however, their feasibility in daily clinical practice remains questionable. Therefore, the 3-item visual analog scale (3VAS) and 4-item VAS (4VAS) were developed; these are shortened composite measures derived from the GRAPPA Composite Score (GRACE) measure.³ This study aimed to validate the 3VAS and 4VAS measures in a population of newly diagnosed patients with PsA receiving usual clinical care.

Data were used from the Dutch Southwest Early PsA (DEPAR) study to test correlation with other measures, responsiveness, and discrimination. All components of the 3VAS (physician global assessment [PGA], patient global assessment [PtGA], patient skin) and 4VAS (PGA, PtGA, patient joint, patient skin) were scored on a 0-10 VAS.

In total, 629 patients were included; 51% (n = 318) male patients with a median (IQR) disease duration of 10.0 (IQR 3.6-32.6) months. According to the 3VAS and 4VAS, 70% and 68% of patients had moderate to high disease activity at baseline, respectively. When comparing low disease activity (LDA; including very low disease activity [VLDA]) of the 3VAS and 4VAS to minimal disease activity (MDA), approximately 2/3 of patients in LDA according to both VAS composite measures were also in MDA at 12 months. Both 3VAS (effect size [ES] = 0.48, standardized response mean [SRM] = 0.52) and 4VAS (ES = 0.48, SRM = 0.50) showed responsiveness similar to Disease Activity Index for Psoriatic Arthritis (DAPSA) and Disease Activity Score in 28 joints. Both measures had a strong correlation with DAPSA (r = 0.799- 0.8666), Psoriatic Arthritis Disease Activity Score (r = 0.8903-0.8922), and Routine Assessment of Patient Index Data 3 (r = 0.8434-0.9247).

Both measures have promising performance characteristics, with strong correlations with existing composite measures and good discriminatory power. Recommended areas for additional research include further refinement of thresholds of meaning, testing feasibility of the 3VAS and 4VAS in daily practice, and testing longitudinal construct validity.

Therapeutic exploration of probiotic strain Lactobacillus reuteri in Western diet–induced psoriatic skin inflammation (Daisuke Yamada and Samuel T. Hwang; 2020 awardees)

The literature suggests that diet affects the severity and incidence of human psoriasis, but the mechanism remains unclear. We previously showed that changes in the gut microbiota due to Western diet (WD) enhanced inflammation in a mouse psoriasis model with interleukin 23 minicircle DNA (IL-23 MC).⁴ As the literature suggests that certain probiotics may reduce inflammation, we hypothesized that specific probiotics may restore the dysbiosis observed in WD-fed mice. We performed the following experiments in standard C57BL/6 mice. Oral gavage of the probiotic Lactobacillus reuteri improved WD IL-23 MC–induced skin inflammation in the mouse model, but the mice had increased fatty liver compared to WD-fed mice not given L. reuteri. This suggests that liver changes may limit chronic use of L. reuteri to reduce inflammation.

Given these findings, we sought to restore dysbiosis with L. plantarum, another probiotic strain that has already been shown to attenuate weight gain. Neither WD IL-23 MC–induced skin inflammation nor intestinal inflammation was improved by L. plantarum. As we did not observe efficacy of L. plantarum in reducing WD IL-23 MC–induced inflammation, we tested the ability of L. plantarum to reduce inflammation in a mouse model fed WD alone to induce inflammation. Relatively low levels of skin inflammation were generated by WD alone (vs prior results) and the minor inflammation was not attenuated by L. plantarum. We investigated variables such as mice (single-nucleotide polymorphism difference), cage environment, and change in food, but we could not identify the exact cause of WD not causing as much inflammation as we reported previously.

In summary, specific probiotic strains such as L. reuteri can reduce WD IL-23 MC–induced skin inflammation, but can induce fatty liver. We continue to search for probiotics, either alone or in combination, that may reduce skin inflammation without significant adverse effects.

Can magnetic resonance imaging differentiate patients with axial spondyloarthritis from patients with PsA with axial involvement? (Josefina Marin, Natalia Rius, and Enrique Soriano; 2021 awardees)

It is unclear whether magnetic resonance imaging (MRI) appearances of spinal involvement differ between patients with axial spondyloarthritis (axSpA) and patients with axial psoriatic arthritis (axPsA).

The main objective of this cross-sectional study was to compare inflammatory changes at the spinal enthesis level between patients with axSpA and axPsA. Secondary objectives were to compare inflammatory and structural changes of the sacroiliac joints (SIJs) and spine, symmetry of inflammatory changes at the SIJs, and percentage of patients with isolated spinal involvement (spinal inflammatory changes without sacroiliac involvement) between patients with axSpA and axPsA, using MRI.

Patients (37 axSpA and 20 axPsA) underwent a full clinical evaluation and MRI of the SIJ and spine. Patients under biologic treatments were excluded. Patients with axPsA had more enthesitis (Maastricht Ankylosing Spondylitis Enthesitis Score ≥ 1 40% vs 6%; P = 0.004), higher mean BMI, and higher Bath Ankylosing Spondylitis Disease Activity Index than patients with axSpA. More patients with axSpA were HLA-B27 positive (67% vs 22%; P ≤ 0.01) than patients with axPsA.

We found no differences in inflammatory changes in the spine as measured by the Canada-Denmark scoring system (CANDEN), in structural changes of the spine and SIJ as measured by the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ Structural Score (SSS) and by CANDEN, in asymmetry at the SIJ (radiograph and MRI), and in the prevalence of isolated inflammatory spinal involvement (21% SpA vs 43%: PsA; P = 0.14). However, there were some differences in inflammatory changes in the SIJ (81% SpA vs 55%: PsA P ≤ 0.03) and a positive correlation between C-reactive protein and SSS in SpA (r = 0.33; P = 0.049).