Assessing Responsiveness of Outcome Measures for Children with Axial Juvenile Spondyloarthritis (JSpA)

Timothy Brandon¹, Rui Xiao², Cassandra Muir¹, Matthew Stoll³, Daniel Lovell⁴, Edward Oberle⁵, Nancy Chauvin⁶, Michael Francavilla⁷, Walter Maksymowych⁸ and Pamela Weiss⁹, ¹Children's Hospital of Philadelphia, Philadelphia, PA, ²University of Pennsylvania, Philadelphia, PA, ³University of Alabama at Birmingham, Birmingham, AL, ⁴Cincinnati Children's Hospital Medical Center, Cincinnati, OH, ⁵Nationwide Children's Hospital, Columbus, OH, ⁶The Imaging Institute @ The Cleveland Clinic, Cleveland, OH, ⁷Department of Radiology, Whiddon College of Medicine, University of South Alabama, Mobile, AL, ⁸University of Alberta, Edmonton, AB, Canada, ⁹Children's Hospital of Philadelphia, Philadelphia, PA

Meeting: ACR Convergence 2024

Keywords: Anti-TNF Drugs, Magnetic resonance imaging (MRI), Outcome measures, Pediatric rheumatology, spondyloarthritis

Session Information

Date: Sunday, November 17, 2024

Title: SpA Including PsA – Diagnosis, Manifestations, & Outcomes Poster II

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Trials for patients with juvenile spondyloarthritis (JSpA) and axial disease are scarce. We assessed the responsiveness of measures for use in trials of patients with axial JSpA.

Methods: This was a 4-center, prospective, observational study of tumor necrosis factor inhibitor (TNFi)-naïve patients with JSpA and axial arthritis starting TNFi therapy. Participants were ages 8 to 18 years and met the International League of Associations for Rheumatology (ILAR) juvenile idiopathic arthritis criteria for enthesitis-related arthritis (ERA) or psoriatic arthritis (PsA) OR European Spondyloarthritis Study Group criteria for SpA. All subjects completed study visits (questionnaires and magnetic resonance imaging [MRI]) at baseline and 12 weeks after TNFi initiation. Subjects with continued subchondral sacroiliac joint (SIJ) inflammation on MRI at 12 weeks, as determined by 1 rater’s global assessment, completed an additional survey and MRI at 24 weeks. At study end, all MRI scans underwent central review by 3 raters; inflammation was scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS). Change scores and standardized mean difference (SMD) for all measures were calculated. Subjects were considered clinical responders if they reported meaningful improvement from the index visit.

Results: 110 visits among 45 unique subjects were included. The cohort was 67% male, 76% white, and had a median age of 14.6 years (IQR 13.1-16.8). 44% were HLA-B27+ and 10% had a family history of SpA. 38% had peripheral arthritis and 66% had enthesitis. Table 1 shows change scores and proportions achieving response outcomes. At the 12-week visit, 80% of youth self-reported a global improvement of moderate or large importance to TNFi therapy and 64.1%/56.4%/43.6%/28.2% met criteria for the ACR 30/50/70/90, respectively. MRI SIS improved from index visit to week 12 in 89% of patients. 22/45 (48.9%) and 12/20 (60.0%) had continued inflammation on MRI at 12 and 24 weeks, respectively. Of those with continued MRI inflammation at 12 weeks, the median SIS and SIS change from index visit were 3 and -7, respectively, and 77% reported clinical improvement of at least moderate importance. SMDs of each measure are shown in Figure 1. Measures with the largest SMD between index and 12-week visit were physician global VAS (1.9), JSpADA-7 index (1.4), and MRI SIS (1.3). Change in the SIS is shown in Figure 2 by clinical responder status; most of the improvement (84% of total baseline SIS across all subjects) occurred between the index visit and week 12. Of the 6 clinical non-responders, only 2 had a worsening of the SIS.

Conclusion: 80% of youth with SpA and sacroiliitis had a clinical response of moderate or large importance to TNFi therapy by 12 weeks. Half of the subjects had continued MRI inflammation at 12 weeks, 77% of which reported clinical improvement of at least moderate importance. Standard pediatric clinical trial calculated response metrics may underestimate clinical response in children with axial disease, underscoring the need for a more responsive set of criteria for this population.

Legend. All raw scores generated from Patient-Reported Outcomes Measurement Information System (PROMIS) instruments are translated into standardized T-scores with a population mean of 50 and standard deviation of 10. Higher scores in a domain represent more of the trait being measured; higher T-scores indicate a worse outcome in the following domains: fatigue and pain interference; lower T-scores indicate a worse outcome in the remaining domains. The Bath Ankylosing Spondylitis Disease Activity Index range is 0_10, with higher scores indicated more active disease. The Bath Ankylosing Spondylitis Functional Index range is 0_10, with higher scores indicating more impairment. All visual analogue scale ranges were 0_10, with higher scores indicating a worse state. The Juvenile Spondyloarthritis Disease Activity (JSpADA) index consists of 8 equally weighted measures and is scored 0-8 with higher score indicating more active disease; the 7-component variant excluding the modified Schober’s test has a score range of 0-7 and is presented in this table. ASDAS-CRP = Ankylosing Spondylitis Disease Activity Score with C-reactive protein, with higher score indicating more active disease; SPARCC SIS = Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint inflammation score (SIS)
*At the 24-week visit, 20 subjects completed the MRI, 19 subjects completed the study questionnaires, and 19 subjects underwent physical examination during a routine clinic appointment.

Figure 1. Standardized mean difference of outcome measures. Standardized Mean Difference (SMD) of measures from 0 to 12 (green bars) and 0 to 24 weeks (blue bars). SMD values of 0.2-0.5 are considered small, 0.5 to 0.8 medium and values >0.8 large. Responses available for a maximum of 45 patients at week 12 and 20 patients at week 24, specific number of responders for each measure at each time point are reported in Table 1. PROMIS = Patient-Reported Outcomes Measurement Information System; VAS = visual analogue scale, BASFI = Bath Ankylosing Spondylitis Functional Index; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; ASDAS-CRP = Ankylosing Spondylitis Disease Activity Score with C-reactive protein; SPARCC = Spondyloarthritis Research Consortium of Canada; JSpADA = Juvenile Spondyloarthritis Disease Activity

Figure 2. Change in sacroiliac joint inflammation score by clinical response status. The Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint inflammation score (SIS) evaluates the presence, depth, and intensity of bone marrow inflammation and scores range from 0-72, with higher scores indicating more inflammation.

Disclosures: T. Brandon: None; R. Xiao: None; C. Muir: None; M. Stoll: None; D. Lovell: AstraZeneca, 12, Consultant, money paid to employer, not individual, Bristol-Myers Squibb(BMS), 5, 12, Contract, money paid to employer, not individual, GlaxoSmithKlein(GSK), 12, Consultant, money paid to employer, not individual, Janssen, 12, Contract, money paid to employer, not individual, Novartis, 12, Consultant, money paid to employer, not individual, Pfizer, 12, DSMB, money paid to employer, not individual, 12, Consultant, money paid to employer, not individual, Roche, 12, Contract, money paid to employer, not individual, United Bioscience Corporation, 12, Consultant, money paid to employer, not individual; E. Oberle: None; N. Chauvin: None; M. Francavilla: None; W. Maksymowych: AbbVie, 2, 5, 6, Boehringer Ingelheim, 2, 6, Bristol Myers Squibb (BMS), 2, 6, CARE Arthritis Limited, 4, Celgene, 2, 6, Eli Lilly, 2, 6, Galapagos, 2, 5, 6, Janssen, 2, 5, 6, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, UCB Pharma, 2, 5, 6; P. Weiss: Abbvie, 12, Clinical trial site PI, NIH NIMAS, 5, PCORI, 5, Pfizer, 1, Spondylitis Association of America, 5.

To cite this abstract in AMA style:

Brandon T, Xiao R, Muir C, Stoll M, Lovell D, Oberle E, Chauvin N, Francavilla M, Maksymowych W, Weiss P. Assessing Responsiveness of Outcome Measures for Children with Axial Juvenile Spondyloarthritis (JSpA) [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/assessing-responsiveness-of-outcome-measures-for-children-with-axial-juvenile-spondyloarthritis-jspa/. Accessed .

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