Fluorescence Optical Imaging for Treatment Monitoring in Patients With Early and Active Rheumatoid Arthritis in a 1-Year Follow-Up Period

Anne-Marie Glimm; Lisa Ines Sprenger; Ida Kristin Haugen; Ulrich Mansmann; Sandra Hermann; Thomas Häupl; Paula Hoff; Gerd-Rüdiger Burmester; Marina Backhaus; Lien Le; Sarah Ohrndorf

Disclosures

Arthritis Res Ther. 2019;21(209) 

In This Article

Results

Patients' characteristics are presented in Table 1. Our analyses focused on the 35 of 42 patients who completed the study after 12 months.

Clinical Parameters

During 12 months follow-up, we found statistically significant reductions in TJC 7.0 (3.5;15) to 1.0 (0;3) and SJC 5.0 (3;9.5) to 1.0 (0;2), respectively (each p < 0.001; see Table 2).

At baseline, patients had high disease activity with median DAS28(ESR) of 5.61 (4.8;6.23). After 1 year, disease activity was statistically significantly reduced to a median DAS28 of 3.31 (2.45;3.98) (p < 0.001) which corresponds to moderate disease activity (see Table 2). By the end of the study, 31.4% (11/35) of patients had achieved remission (DAS28 < 2.6).

Fluorescence Optical Imaging (FOI)

Statistically significant reductions were detected in the FOI sum score (FOIAS) in phase 1 from baseline (5.0, (1.04; 26)) to 12 months follow-up (1.0 (0; 4)) in the total patient cohort (p = 0.0045). There were no statistically significant changes in the FOI sum score in phase 2, phase 3, or PVM in the total cohort (see Table 3 and Figure 1 and Additional file 1: Table S2 (analysis without DIP).

Figure 1.

Reduction of early enhancement in FOI (fluorescence optical imaging) phase 1 after 12 months follow-up: a V0: Example with early high enhancement in phase 1 before ICG flooding in the fingertips, especially in the wrists, PIPs, and IPs of both hands. Moderate enhancement in MCP II and IV of the right hand. V12: High physiological enhancement in the fingertips in phase 1 after 12 months. No enhancement in the finger and hand joints. b Example of early enhancement in phase 1 in both hands, especially in MCP II and III of the right hand. High enhancement also in PIPs of both hands, left wrist, and MCP II and III. Physiological signal in the fingertips. V12: High physiological enhancement in the fingertips in phase 1 after 12 months. No significant enhancement in the finger and hand joints. V0: baseline, V12: follow-up after 12 months

Correlation of FOI and Clinical Parameters

Regarding baseline data, no significant positive correlation between FOI and clinical parameters (TJC, SJC, and DAS28(ESR)) can be shown (see Figure 2a).

Figure 2.

Pairwise correlation between the number of affected joints in clinical examination and FOI phases 1, 2, and 3 and PVM: significance level = 0.05; FOI = fluorescence optical imaging; PVM = PrimaVistaMode; SJC = swollen joint count; TJC = tender joint count; DAS28(ESR) = Disease Activity Score of 28 joints and erythrocyte sedimentation rate (ESR); VAS = visual analog scale. Spearman's correlation coefficients and p values are presented. a measurement at V0 (baseline) b change at V12 (12 months follow-up)

FOI in phase 1 showed no statistically significant correlations with clinical data concerning the analysis of clinically affected joints and FOI after 12 months follow-up (see Figure 2b). FOI phases 2 and 3 demonstrated weak to moderate correlations with DAS28(ESR) and SJC. PVM correlated significantly with all three clinical parameters. While the correlation with TJC was only weak (r = 0.38), PVM correlated moderately with SJC and DAS28(ESR) (r = 0.58, r = 0.51, see Figure 2b). The corresponding p values of the correlation coefficients were < 0.05. An additional statistical analysis performed without the DIP joints in FOI did not change the level or direction of correlation (for further data see Additional file 1: Table S3a and Table S3b).

Correlations Between FOI and US

US data of baseline and after 12 months are presented in Table 2.

With respect to the calculated correlations in the total group, tenosynovitis in greyscale ultrasound (GSUS) and PDUS correlated with every phase and PVM at baseline, but strongest for PD-tenosynovitis with phase 2 (r = 0.73; p < 0.05). With regard to GS- and PD-synovitis, significant positive correlations with phase 1, phase 2, and PVM at baseline can be shown. While GS-synovitis most strongly correlated with PVM in FOI (r = 0.6), the strongest correlation between PD-synovitis and FOI was demonstrated for phase 1 (r = 0.59) (Figure 3a).

Figure 3.

Pairwise correlation between US7 and FOI phase 1, 2, and 3 and PVM: significance level = 0.05; FOI = fluorescence optical imaging; PVM = PrimaVistaMode; PD = power Doppler mode in ultrasound, GS = greyscale mode in ultrasound. Spearman's correlation coefficients and p values are presented. a measurements at V0 (baseline) b change at V12 (12 months follow-up)

After 12 months, FOI in phase 2 demonstrated the strongest correlations, especially with PD-tenosynovitis (r = 0.63; p < 0.05) and GS-tenosynovitis (r = 0.59; p < 0.05). For phase 1, low correlation with GS-synovitis can be demonstrated (r = 0.48, p < 0.05). However, PVM was the only FOI part correlating with all considered US parameters (Figure 3b).

Comparison of Clinical Findings and FOI in Responders vs. Non-responders

According to the EULAR response criteria,[32] n = 16 (45.7%) patients were defined as responders (DAS28(ESR) ≤ 3.2 and improvement of > 0.6) and n = 19 (54.3%) as non-responders (DAS28(ESR) > 3.2).

Regarding the responders (DAS28(ESR) ≤ 3.2 and improvement of > 0.6; n = 16) and non-responders (DAS28(ESR) > 3.2; n = 19), both groups demonstrated a statistically significant decline in affected tender and swollen joints after 12 months. Non-responders had a greater number of tender (11 (5.5;18.5)) and swollen (6; (3.5;9.5)) joints at baseline than the group of responders (TJC: 4.5 (3;10.5) and SJC: 3.5 (1.75;8.25), respectively). After 12 months, the number of tender and swollen joints decreased to 0 in responders (see Table 2). In non-responders, the median number of tender joints and swollen joints was 3 (1.5;11) and 1 (0;4), respectively (see Table 2).

With regard to US7 score parameters, the group of responders showed significant decrease in all US7 parameters, while the group of non-responders revealed significant decrease only in PD-synovitis.

We found no statistically significant difference in the change of the FOI sum score between responders and non-responders for the FOI phases 2 and 3 and PVM relating to EULAR response criteria[32–34] for low disease activity. In FOI phase 1, the difference in the change of FOI sum score was similar in non-responders (p = 0.047) and responders (p = 0.052) (see Figure 4a). There were no statistically significant differences across patients who did vs. did not achieve remission for FOI phases 2 and 3 and PVM. For FOI phase 1, statistically significant difference was shown only in responders regarding clinical remission status (see Figure 4b).

Figure 4.

a Course of FOI sum scores in comparison to EULAR response criteria of "low disease activity" according to DAS28. b Course of FOI sum scores in comparison to EULAR response criteria of "remission" according to DAS28: non-responder (DAS28(ESR) > 3.2), responder (DAS28(ESR) ≤3.2 and improvement of > 0.6). FOI = fluorescence optical imaging; DAS28 = Disease Activity Score of 28 joints. V0 (red): baseline, V12 (blue): follow-up after 12 months

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