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

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Arthritis Res Ther. 2019;21(209)

Abstract and Introduction

Abstract

Background: Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies.

Objective: To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration < 2 years) and active (DAS28 > 3.2) RA over a period of 12 months.

Methods: Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1–3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0–90).

Results: We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p < 0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate.

Conclusion: Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively.

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Arthritis Res Ther. 2019;21(209) © 2019 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Abstract and Introduction
Background
Methods
Results
Discussion
Conclusions
References

Table 1. Patients' characteristics at baseline
		Summary statistics
Age (n = 35)	At the beginning of the study	53.32 (13.63) (22.23;74)
Age (n = 35)	Number of patients ≥ 65 years (LORA)	8/35 (22.86%)
Gender (n = 35)	Female	24/35 (68.57%)
Disease duration (n = 35)	Duration from initial diagnosis until inclusion in the study (in months)	0.2 (0.42) (0;1.98)
Disease duration (n = 35)	Duration of symptoms (in months)	1.3 (1.25) (0.13;4.5)
Disease Activity Score 28 (DAS28)	DAS28(ESR) (n = 34)	5.55 (1.11) (3.55;7.57)
Disease Activity Score 28 (DAS28)	DAS28(CRP) (n = 31)	5.02 (1.12) (3.09;6.77)
Laboratory parameters	ESR (1 h/mm) (n = 34)	39.62 (22.23) (8;95)
Laboratory parameters	CRP (n < 5.0 mg/l) (n = 32)	16.34 (17.89) (0;66.52)
Clinical examination (n = 35)	Swollen joint count (28-SJC)	6.31 (4.73) (1;20)
Clinical examination (n = 35)	Tender joint count (28-TJC)	10.26 (7.85) (1;25)
VAS (0–100 mm) for disease activity	Patient (n = 35)	58.14 (18.79) (20;100)
VAS (0–100 mm) for disease activity	Physician (n = 21)	54.52 (16.58) (30;90)
Rheumatoid factor (RF)	Seropositive (n = 34)	15/35 (42.86%)
	Rheumatoid factor IgA (n = 29)	93.23 (166.03) (0.1;500)
	Rheumatoid factor IgM (n = 31)	59.64 (113.93) (0.1;500)
Anti-citrullinated peptide antibodies (ACPA) (n = 35)	Level	250.34 (393.27) (0.42;1000)
	Positive	4/35 (11.43%)
	Highly positive	15/35 (42.86%)

Patients' characteristics at baseline: mean (SD); (min; max) or n (%); DAS28 Disease Activity Score of 28 joints, ESR erythrocyte sedimentation rate, CRP C-reactive protein

Table 2. Clinical and ultrasound parameters at baseline and after 12 months in total population, group of responders and non-responders
	Month of visit 0 (V0)*	Month of visit 12 (V12)*	Difference between V12 and V0*	p value (Wilcoxon signed rank test)
Total population (n = 35 for clinical, n = 34 for US7 parameters)
28-SJC	5 (3;9.5) (1;20)	1 (0;2) (0;10)	−4 (−7;− 1) (−19;3)	< 0.001 (sig.)
28-TJC	7 (3.5;15) (1;25)	1 (0;3) (0;26)	−4 (− 10;− 1) (−24;6)	< 0.001 (sig.)
DAS28(ESR)	5.61 (4.8;6.23) (3.55;7.57)	3.31 (2.45;3.98) (1.13;6.19)	−2.22 (−3.11;− 1.39) (−5.45;0.56)	< 0.001 (sig.)
GS-synovitis	7 (5.5;9.5) (2;15)	6 (4.25;7) (2;10)	− 1 (−3;0) (−9;7)	0.0112 (sig.)
GS-tenosynovitis	3 (2;4) (0;5)	2.5 (2;3) (0;4)	−0.5 (−1.75;0) (−4;2)	0.0239 (sig.)
PD-synovitis	4 (3;7) (2;15)	3 (2;3.75) (0;11)	−1 (−3;0) (−9;1)	0.00004 (sig.)
PD-tenosynovitis	3 (2;4) (0;7)	2 (1.25;3) (0;5)	0 (−2;0.75) (−4;1)	0.0163 (sig.)
Group of responders (n = 16)
28-SJC	3.5 (1.75;8.25) (1;15)	0 (0;1) (0;3)	−3.5 (−8.25;− 1) (−14;1)	0.002 (sig.)
28-TJC	4.5 (3;10.5) (1;24)	0 (0;0.25) (0;2)	−3.5 (−10.5;− 3) (−24;− 1)	< 0.001 (sig.)
DAS28(ESR)	4.88 (4.33;6.18) (3.55;7.33)	2.38 (1.89;2.68) (1.13;3.18)	−2.82 (−3.82;− 1.82) (−5.45;− 1.14)	< 0.001 (sig.)
GS-synovitis	8 (6;9.25) (2;12)	6 (4;7) (3;9)	−2 (−4.25;0) (−9;7)	0.038 (sig.)
GS-tenosynovitis	4 (2.75;5) (1;5)	2.5 (2;3) (1;4)	−1 (−2;0) (−4;2)	0.0274 (sig.)
PD-synovitis	4 (3.75;6.5) (2;11)	3 (2;3) (1;4)	−2 (−5;− 0.75) (−8;1)	0.0028 (sig.)
PD-tenosynovitis	3 (2;5) (1;7)	2 (2;3) (1;3)	−1 (−2.25;0) (−4;1)	0.01 (sig.)
Group of non-responders (n = 19 for clinical, n = 18 for US7 parameters)
28-SJC	6 (3.5;9.5) (1;20)	1 (0;4) (0;10)	−5 (−6.5;− 2) (−19;3)	0.001 (sig.)
28-TJC	11 (5.5;18.5) (1;25)	3 (1.5;11) (0;26)	−4 (−8;0.5) (−22;6)	0.01 (sig.)
DAS28(ESR)	5.82 (5.34;6.23) (3.61;7.57)	3.95 (3.51;5.21) (3.28;6.19)	−1.62 (−2.61;− 0.51) (−3.73;0.56)	< 0.001 (sig.)
GS-synovitis	7 (4.5;9.5) (2;15)	6 (5;8.5) (2;10)	−1 (−2;0.75) (−5;6)	0.1641
GS-tenosynovitis	2 (2;4) (0;5)	2.5 (1;3) (0;4)	0 (−1;1) (−3;2)	0.506
PD-synovitis	4 (2.5;7) (2;15)	3 (1;5) (0;11)	−1 (−2;0) (−9;1)	0.0058 (sig.)
PD-tenosynovitis	2 (1;3) (0;7)	2.5 (1;3) (0;5)	0 (−0.75;1) (−4;1)	0.7732

Clinical and ultrasound (US) parameters at baseline and after 12 months in total population, group of responders and non-responders: *Median (1. quartile; 3. quartile); (min; max), significance level = 0.05; 28-SJC swollen joint count of 28 joints, 28-TJC tender joint count of 28 joints, DAS28(ESR) Disease Activity Score of 28 joints and erythrocyte sedimentation rate (ESR), GS greyscale mode in ultrasound, PD Power Doppler mode in ultrasound

Table 3. FOIAS of phases 1–3 and PVM (PrimaVistaMode) in FOI at baseline and after 12 months ( n = 35 for FOIAS parameters
	Month of visit 0 (V0)*	Month of visit 12 (V12)*	Difference between V12 and V0*	p value (Wilcoxon signed rank test)
Phase 1	5 (1.04;26) (0;70.91)	1 (0;4) (0;32)	−3 (− 17;0) (−69.91;12)	0.00445 (sig.)
Phase 2	16 (10.5;25) (1;40)	16 (9.5;24) (2;43)	2 (−4.5;6.81) (− 18;18)	0.6004
Phase 3	1 (0;2.5) (0;15)	1 (0;4) (0;10)	0 (− 1;1.5) (− 12;9)	0.5451
PVM	9 (4.5;13) (0;24)	9 (3.5;14) (0;26)	−1 (−4;4) (− 15;14)	0.7461

Phases 1–3 and PVM (PrimaVistaMode) of FOI at baseline and after 12 months (n = 35): FOIAS fluorescence optical imaging activity score; *median (1. quartile; 3. quartile); (min; max); significance level = 0.05

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