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Abstract Number: 252

Cytokine Profiles of Korean Patients with Adult Onset Still’s Disease Treated with Biologic Agents

Seung Taek Song1, SuMan Kang2, Sung Won Lee3, Seoung Wan Nam2, Hyukhee Kwon2 and Dae-Hyun Yoo4, 1Division of Rheumatology, Department of Internal Medicine, Cheongju St. Mary's Hospital, Cheongju, Korea, The Republic of, 2Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea, The Republic of, 3Department of Rheumatology, Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, 4Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Adult-onset Still's disease, anti-TNF therapy, cytokines and tocilizumab

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Session Information

Date: Sunday, November 13, 2016

Session Title: Miscellaneous Rheumatic and Inflammatory Diseases - Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:  Adult onset Still’s disease (AOSD) is a rare inflammatory disorder of unknown etiology. Several studies have reported that pro-inflammatory cytokines including interleukin (IL)-1, IL-6, IL-18, tumor necrosis factor (TNF)-α, and interferon (INF)-γ, are involved in the pathogenesis of AOSD. Refractory AOSD patients have been treated successfully with anti-cytokine biologics. Herein, we analyzed cytokines to investigate predictors for therapeutic response of biologic drugs in refractory AOSD.

Methods:  Twenty two AOSD patients who treated with anti-TNFα agents or anti-IL-6 receptor agent were recruited from a university hospital for rheumatic diseases in Korea. The dosages of anti-TNFα (infliximab in 18 patients, etanercept in 4, and adalimumab in 3) and tocilizumab in 12 were same as those of rheumatoid arthritis. Serum cytokines (TNFα, IL-1β, IL-6, IL-8, IL-17α, and INF-γ) and IL-2 receptor α were analyzed by multiplex flowcytometry. A good response to biologic agents was defined as decreased modified Pouchot score more than 2 score compared to initial treatment of biologic agents. A no response to biologic agents was defined as no decrease of modified Pouchot score. We used the Mann-Whitney test for continuous variable.

Results:  Seven (36.8%) patients showed good response to anti-TNFα inhibitors and 3 (13.6%) patients showed partial response. Nine (47.4%) patients did not respond to anti-TNFα inhibitors. Three (25%) patients showed good response to tocilizumab (TCZ), 4 (33.3%) showed partial response, and 5 (41.7%) showed no response. At starting time point of anti-TNFα inhibitors, levels of TNFα, IL-1β, IL-6, and IFNγ in no responders was higher compared to those with good response, but without statistically significant differences (Table 1). At starting time point of TCZ, conversely, the levels of TNFα and IL-6 in no responders was lower compared to responders including good and partial response (Table 2). We didn’t raise the dosage of infliximab in no responders, nine patients, in whom TCZ was used as second biologic therapy. Of those, five (55.6%) patients showed improvement in clinical and laboratory findings.

Conclusion:   This study showed that AOSD patients who were refractory to biologic agents might have distinct cytokine profiles. Therefore, dosage and sort of biologic agents in AOSD patients might be individualized according to pre-treatment cytokine profiles.

Table 1. Cytokine levels of AOSD patients before anti-TNFα therapy.
 

Total

(n = 19)

Good response

(n = 7)

No response

(n = 9)

p

TNFα (pg/mL)

11.19 (20.06)

6.34 (9.71)

14.96 (25.43)

0.632

IL-1β (pg/mL)

6.23 (13.25)

2.32 (2.70)

9.65 (17.79)

0.600

IL-2Rα (pg/mL)

676.47 (593.44)

971.12 (790.92)

447.30 (236.86)

0.101

IL-6 (pg/mL)

54.52 (126.31)

45.34 (77.11)

61.66 (159.13)

0.427

IL-8 (pg/mL)

41.96 (73.61)

69.19 (100.55)

20.77 (37.73)

0.396

IL-17α (pg/mL)

0.77 (1.01)

0.50 (0.32)

0.97 (1.32)

0.745

IL-18 (pg/mL)

42,339.33 (60,876.27)

65,983.73 (79,663.30)

21,650 (30,396.91)

0.165

 INFγ

48.27 (117.13)

11.99 (8.87)

76.49 (153.67)

0.708

Values are the mean (SD) unless otherwise indicated.
Of 19 AOSD patients, three was partial response.
Mann-Whitney test

 

Table 2. Cytokine levels of AOSD patients before anti-IL-6 receptor therapy.
 

Total

(n = 12)

Response

(n = 7)

No response

(n = 5)

p

TNFα (pg/mL)

12.70 (25.63)

13.80 (33.51)

11.17 (10.83)

0.048

IL-1β (pg/mL)

9.29 (19.92)

10.40 (25.00)

7.35 (8.10)

0.927

IL-2Rα (pg/mL)

559.34 (329.61)

611.73 (398.97)

485.99 (220.16)

0.755

IL-6 (pg/mL)

31.15 (32.71)

39.38 (32.61)

19.63 (32.61)

0.268

IL-8 (pg/mL)

22.90 (31.92)

23.90 (40.28)

21.51 (19.07)

0.343

IL-17α (pg/mL)

1.29 (1.00)

1.01 (0.53)

1.68 (1.42)

0.639

IL-18 (pg/mL)

39,062.61 (43,665.18)

49,258.95 (45,788.29)

23,768.10 (41,301.81)

0.171

 INFγ

54.55 (94.18)

56.73 (115.54)

51.49 (65.94)

0.639

Values are the mean (SD) unless otherwise indicated. Mann-Whitney test


Disclosure: S. T. Song, None; S. Kang, None; S. W. Lee, None; S. W. Nam, None; H. Kwon, None; D. H. Yoo, None.

To cite this abstract in AMA style:

Song ST, Kang S, Lee SW, Nam SW, Kwon H, Yoo DH. Cytokine Profiles of Korean Patients with Adult Onset Still’s Disease Treated with Biologic Agents [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/cytokine-profiles-of-korean-patients-with-adult-onset-stills-disease-treated-with-biologic-agents/. Accessed March 23, 2023.
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