Is a simplified version of PsAMRIS (sPsAMRIS) a potential tool for therapy monitoring in established psoriatic arthritis?

Background: To evaluate whether a simplified version of the resonance imaging score (PsAMRIS), (PsA). Methods: Seventeen patients with PsA, according to CASPAR classification criteria, with inadequate methotrexate response received anti-TNF treatment and were assessed by 3T MRI of the clinically dominant hand at baseline and after 6 months. Scoring was according to PsAMRIS. Items were reduced based on standard response mean (SRM), resulting in a simplified PsAMRIS (sPsAMRIS), which was compared to PsAMRIS by calculation of the total SRM and relative efficiency (RE) after bootstrapping. Results: The PsAMRIS subscore of MCP3, 4, and PIP4 resulted in the highest SRM (–0.07 each) and were, therefore, included in sPsAMRIS. sPsAMRIS had a higher SRM compared to PsAMRIS (– 0.13 vs. –0.02) and a higher RE (29.46). PsAMRIS and sPsAMRIS were highly correlated at baseline (r=0.75, p<0.01) and follow-up (r=0.64, p=0.01). The evaluation time was reduced from 471 to 142 seconds at baseline and from 478 to 133 seconds at follow-up (p<0.001). Conclusions: sPsAMRIS is a potential tool for therapy monitoring in psoriatic arthritis and is a time-saving variation of OMERACT PsAMRIS.


Image analysis
MR images were read and analyzed in consensus by two radiologists and one rheumatologist trained in PsAMRIS-Scoring, according to the OMERACT PsAMRIS guidelines [15,16]. In the case of different scores, the analysts decided scorings by common agreement. Images were evaluated for synovitis (score 0-3), flexor tenosynovitis (score 0-3), periarticular inflammation (score 0 or 1), bone edema (score 0-3), bone erosion (score 0-10), and bone proliferation (score 0 or 1) for the MCP (metacarpophalangeal), PIP (proximal interphalangeal), and DIP (distal interphalangeal) joint region of fingers 2-5, according to the OMERACT PsAMRIS guidelines [15]. In all joints, the proximal and distal or the dorsal and palmar portions, respectively, were analyzed separately for the presence of bone edema and erosions or periarticular inflammation. For comparison of time effort, one highly trained radiologist (CS) timed the scoring of PsAMRIS and sPsAMRIS.

Development of a simplified psoriatic arthritis MRI score, sPsAMRIS
For the development of a simplified scoring system, sPsAMRIS, we applied a single-site weighted summation approach. Priority was assigned to the joints with the highest standardized response mean (SRM) for the change of overall PsAMRIS at baseline and at follow up (Table 3) All statistical analyses were performed using the R project for statistical computing (version 3.5.1 "feather spray", the R foundation). For descriptive analysis mean, standard deviation, minimum, and maximum were presented. The sensitivity for change and their responsiveness was calculated by SRM for PsAMRIS and sPsAMRIS, as follows: SRM= . Relative efficiency (RE) was calculated for sPsAMRIS compared to PsAMRIS as a reference, as follows: RM= 2 . Confidence bounds for the RE were estimated by the bootstrap method (based on B=5000 bootstraps with replacement) and application of the percentile method. A RE>1 indicates that sPsAMRIS is more efficient than PsAMRIS in detecting change. For correlation analyses, Pearson's product-moment correlation with Pearson's correlation coefficient, r, was used. A p-value of <0.05 was considered to be significant. Inter-and intra-rater reliability was calculated by two-way mixed intraclass correlation coefficients [single-measure ICC (sICC) for intra-rater and average-measure ICC (aICC) for inter-rater reliability].

Simplified score: sPsAMRIS
Change of overall PsAMRIS and each PsAMRIS item between baseline and follow-up assessed by SRM is summarized in Table 1. Regarding overall PsAMRIS, MCP3, MCP4, and PIP 4 show the highest SRM (0.07, -0.07 and -0.07) and are hence combined as a new, simplified score: sPsAMRIS (s. Figure 1).

PsAMRIS and sPsAMRIS over the course of therapy
The PsAMRIS and sPsAMRIS results regarding the overall scores and each subscore at baseline under MTX therapy and at follow-up, after escalation to etanercept, are summarized in Table 2. Synovitis, flexor tenosynovitis, and periarticular inflammation are frequently found using both PsAMRIS and sPsAMRIS (examples in figure 2). Bone edema and bone erosions, on the other hand, are less frequently seen, whereas bone proliferations are rarely detected.
At follow-up, overall PsAMRIS and sPsAMRIS, as well as subscores for synovitis, bone proliferations, periarticular inflammation, and bone erosions, were increased. Flexor tenosynovitis and bone edema, on the other hand, were improved at follow-up.

PsAMRIS and sPsAMRIS sensitivity to change/responsiveness assessed by the standardized response mean (SRM)
The sensitivity to change of PsAMRIS and sPsAMRIS was assessed by SRM [18] and is summarized in Table 3. Common thresholds for SRM are the following: large, ≥0.8; moderate, 0.5-0.8; small, 0.2-0.5; trivial, ≤0.2 Overall there is trivial sensitivity to change measured by PsAMRIS and sPsAMRIS, whereas the latter shows a slightly higher sensitivity. Only periarticular inflammation and bone erosion measured by PsAMRIS and synovitis measured by sPsAMRIS showed a higher, but still low, sensitivity.

Correlation of PsAMRIS and sPsAMRIS
Correlation of PsAMRIS and sPsAMRIS is shown in Table 4. There was a strong correlation between PsAMRIS and sPsAMRIS regarding the overall values at baseline and at follow-up after escalation etanercept therapy (baseline, r=0.75, p<0.01; follow-up, 0.64, p<0.05). Also, there was a strong correlation regarding most subscores. DIP-and to a lesser extent PIP-joints due to a lack of spatial resolution, there is additional weight for an abbreviation with focus especially on the MCP-region [15,16]. Using an MRI with an even higher field, 3 T against 1.5 T, and a dedicated 16-channel hand coil, spatial resolution is considerably improved, making analysis of the PIP region more accurate. With sPsAMRIS containing only MCP 3, 4, and PIP 4, the initial concerns with the known PsAMRIS mentioned above should be resolved or significantly improved with sPsAMRIS.

PsAMRIS and sPsAMRIS: Time comparative analysis
Our study has limitations. Since PsA is a disease with several ways of clinical and radiological presentation, this study focused more on a well-defined and homogeneous than on a large patient collective. However, due to our small patient collective, further investigations with larger cohorts are required to confirm our results and the eligibility of sPsAMRIS. Further, as mentioned above, sPsAMRIS is a data-driven, weighted approach that is derived from a certain patient collective and, hence, could lack applicability for other collectives. Since PsA is a very heterogeneous and complex disease, a "one fits all" scoring system that is both sensitive and timesaving seems more difficult to established, e.g., compared to RA. However, the concept of simplifying regular PsAMRIS could still be beneficial to make it more accessible for daily practice and therapy monitoring. Another potential limitation is using SRM as a statistical means for assessing responsiveness. However, SRM is among the most widely used statistical means [18,32] and, therefore, it is considered to be a reasonable calculation to estimate responsiveness. In our data-driven approach, we chose items based on the absolute amount of the SRM, disregarding the direction of the association. This takes into account that improvement and deterioration of different dimensions (e.g., synovitis, osteitis, tenosynovitis) may coexist in any given patient and/or joint.

Conclusion
The simplified MRI scoring system for PsA-related changes in hands, sPsAMRIS, showed a strong correlation with the known PsAMRIS and, hence, is a potential tool for therapy monitoring in PsA. It can be considered a time-saving simplification to regular PsAMRIS.

Ethics approval
The study was approved by the ethic committee of the medical faculty of the Heinrich-Heine University Duesseldorf (4962R). Written and informed consent was obtained from all patients before the initiation of the study.

Consent for publication
Not applicable.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
The project was funded by the "Pfizer GIP Inflammation Germany Research Initiative 2014" to PS and SV and by a grant from the German "Bundesministerium für Bildung und Forschung"(BMBF), ArthroMark (01EC1009). DBA was supported by an internal research grant of the local research committee of the medical faculty. None of the funding bodies participated in the design of the study, the collection, the analysis, the interpretation of data or in the writing of the manuscript.