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Abstract Number: 604

Calprotectin and TNF Antagonist Serum Trough Levels Identify Active Ultrasound Synovitis in Rheumatoid Arhritis and Psoriatic Arthritis Patients in Remission or Low Disease Activity

Jose Inciarte-Mundo1, Julio Ramírez1, Virginia Ruiz-Esquide1, M. Victoria Hernández1, Oscar Camacho1, Sonia Cabrera-Villalba1, Andrea Cuervo1, Mariona Pascal2, Jordi Yagüe2, Juan D. Cañete1 and Raimon Sanmarti1, 1Rheumatology Department, Hospital Clinic i Provincial, Barcelona, Spain, 2Immunology Department, Hospital Clinic i Provincial, Barcelona, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: anti-TNF therapy, Biomarkers, Psoriatic arthritis, rheumatoid arthritis (RA) and ultrasonography

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Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

An accurate assessment of disease activity is needed in Rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA) patients in remission or low disease activity for clinical decision-making. Calprotectin a major S100 leukocyte protein and TNF antagonist (TNFa) serum trough levels are associated with disease activity. Residual power Doppler ultrasound synovitis (PDUS) is predictive of clinical flare in this group of patients.

Objectives:

To analyze the relationship between PDUS with calprotectin and TNFa serum trough levels in RA and PsA patients in clinical remission or low disease activity. To correlate calprotectin levels with serum trough levels of TNFa.

Methods :

Cross-sectional analysis from a prospective cohort study of RA (ACR 1987) and PsA patients (CASPAR) treated with TNFa [etanercept (ETN), adalimumab (ADA), and infliximab (IFX)] for ≥ 3 months in clinical remission (DAS28-ESR<2.6) or low disease activity (DAS28-ESR<3.2) in ≥2 consecutive visits. The patients underwent clinical, laboratory, and PDUS assessment at visit 4 (12 months of follow-up). Calprotectin serum levels (using kits from Calpro AS) and TNFa serum trough levels (using kits from Promonitor®, Progenika) were determined. A rheumatologist experienced in musculoskeletal ultrasound and blinded to clinical and laboratory data performed US assessment with a high sensitivity equipment (MyLabTwice®, Esaote, Italy. 8-14 MHz linear probe). 22-joint B-mode synovial hypertrophy (SH) and PDUS signal were scored from 0-3 at each joint. Global indices for SH and PDUS signal were calculated. Ultrasound active synovitis (UAS) was defined as intraarticular synovitis detected with power Doppler signal.1

Results :

Ninety-two patients (42 RA, 50 PsA) out of 100 patients included at study entry completed the follow-up at 12 months (visit 4). 43 patients had UAS (27 RA and 16 PsA). UAS patients showed higher disease activity, higher calprotectin levels and lower drug serum trough levels, even when analyzed by diagnostic (RA or PSA) (table 1). When a more stringent UAS criteria were apply (SH grade 2+PDUS)2, only calprotectin can distinguish between them [active (n=15) 3.48(0.2-5.5) vs. inactive (n=77) 1.47(0.06-4.8), p=<0.001]. Calprotectin and serum trough levels inversely correlated with PDUS score in ADA (rho=-.591, p=<0.001 and rho=-.842,p=<0.001,respectively) and ETN (rho=-.313,p=0.039 and rho=-.649,p=<0.001,respectively). Calprotectin serum levels inversely correlated with ADA serum trough levels (rho=-.461, p=0.008), non-significant correlations were observed with ETN and IFX.

Conclusion :

Calprotectin and TNFa serum trough levels may help to identify ultrasound active synovitis in RA and PsA patients in clinical remission/low disease activity.

GLOBAL

(n=92)

RA

(n=42)

PsA

(n=50)

PDUS negative

 (n=49 )

PDUS positive

(n=43)

PDUS negative

 (n=15)

PDUS positive

 (n=27)

PDUS negative

(n=34)

PDUS positive

 (n=16)

Female, n (%)

26 (53.1)

33 (76.7)

11 (73.3)

23 (85.2)

15 (44.1)

10 (62.5)†

Age, median (range), years

56 (33-78)

60 (30-81)

62 (49-78)

64 (30-81)

53 (33-77)

55 (40-72)

Disease duration, median (range) years

13 (1-28)

17 (2-44)

13 (8-28)

17 (2-44)

13.5 (1-28)

16 (3-36)

Concomitant sDMARD, n (%)

22 (44.9)

25 (58.1)

11 (73.3)

21 (77.8)

11 (32.4)

4 (25)

Reduced dose, n (%)

25 (51)

17 (39.5)

4 (26.7)

8 (29.6)

21 (61.8)

9 (56.3)

Calprotectin, median (range), μg/mL

1.0 (0.6-3.7)

2.68 (0.225.54)*

1.44 (0.2-2.4)

2.95 (0.2-5.5)†

0.70 (0.06-3.7)

2.36 (0.9-4.6)*

CRP, median (range), mg/dl

0.07 (0.1-0.6)

0.20 (0.01-1.4)†

0.07 (0.02-0.1)

0.30 (0.01-1.4)†

0.08 (0.01-0.6)

0.09 (0.01-0.3)

ESR, median (range), mm/h

8 (2.-29)

13 (2-43)*

10 (2-24)

13 (2-43)

8 (2-29)

13 (4-32)†

DAS28-ESR, median (range)

1.78 (1-2.7)

2.36 (1.1-3.2)*

2.08 (1.5-2.6)

2.62 (1.3-3.2)†

1.67 (1-2.7)

2.15 (1.1-3.1)†

SDAI, median (range)

6 (2-8)

6 (2-11)†

6.02 (2-8)

6.26 (2-11)†

5.10 (2-8)

6.04 (2-8.3)

CDAI, median (range)

6 (2-8)

6 (2-11)

6 (2-8)

6 (2-11)

5 (2-8)

6 (2-8)

ADA serum trough levels, median (range), μg/mL

7.08 (4.1-12)

1.06 (0.2-12)*

8.39 (4.2-12)

1.68 (0.6-12)†

6.95 (4.1-12)

0.88 (0.2-9.8)†

ETN serum trough levels, median (range), μg/mL

1.69 (0.1-4.7)

0.91 (0.06-2.3)†

2.54 (0.2-4.7)

0.98 (0.7-2.3)†

1.38 (01-3.5)

0.91 (0.6-1.6)

IFX serum trough levels, median (range), μg/mL

3.21 (0.7-7.7)

1.92 (0.1-6.5)†

8.39 (4.2-12)

1.68 (0.6-12)†

3.21 (0.7-7.7)

2.86 (0.1-6.5)

 *p<0.001

†p<0.05

References:

1. Naredo E. Arthritis Rheum.2007;57(1):116-2.

2. Ramírez J. Arthritis Res Ther.2014;16(1):R5.


Disclosure: J. Inciarte-Mundo, Grant from Catalan Rheumatology Society, 2; J. Ramírez, None; V. Ruiz-Esquide, None; M. V. Hernández, None; O. Camacho, None; S. Cabrera-Villalba, None; A. Cuervo, None; M. Pascal, None; J. Yagüe, Novartis Pharmaceutical Corporation, 2; J. D. Cañete, None; R. Sanmarti, Unrestricted grant from Pfizer, 2.

To cite this abstract in AMA style:

Inciarte-Mundo J, Ramírez J, Ruiz-Esquide V, Hernández MV, Camacho O, Cabrera-Villalba S, Cuervo A, Pascal M, Yagüe J, Cañete JD, Sanmarti R. Calprotectin and TNF Antagonist Serum Trough Levels Identify Active Ultrasound Synovitis in Rheumatoid Arhritis and Psoriatic Arthritis Patients in Remission or Low Disease Activity [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/calprotectin-and-tnf-antagonist-serum-trough-levels-identify-active-ultrasound-synovitis-in-rheumatoid-arhritis-and-psoriatic-arthritis-patients-in-remission-or-low-disease-activity/. Accessed .
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