Effect of Tocilizumab on Adults Onset Still's Disease in Korean Population: Multicenter Retrospecitve Study of 24 Cases

Seung Taek Song¹, Jin Ju Kim², Seung Lee¹, Hye-Jin Jeong¹, Il Woong Sohn², Sung Won Lee², Joo Hyun Lee³, Hyoun-Ah Kim⁴, Kwang-Hoon Lee⁵, Sang Tae Choi⁶, Eun Young Lee⁷, Kichul Shin⁸, Hoon-Suk Cha⁹ and Dae-Hyun Yoo¹⁰, ¹Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ²Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ³Department of Rheumatology, Ilsan Paik Hospital, Inje University, Goyang, South Korea, ⁴Ajou University Hospital, Suwon, South Korea, ⁵Dongguk University Ilsan Hospital, Goyang, South Korea, ⁶Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea, ⁷Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea, ⁸Seoul National University College of Medicine, Seoul, South Korea, ⁹Division of Rheumatology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, ¹⁰Division of Rheumatology, Department of Internal Medicine, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Adult-onset Still's disease and tocilizumab

Session Information

Date: Sunday, November 8, 2015

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. Nonsteroidal anti-inflammatory drugs or corticosteroids are first-line drugs for treating AOSD. Immunosuppresants are needed to patients who are refractory to corticosteroids. Recently, it has been reported that biologic agents in AOSD are effective. Although IL-1 targeting therapy is very effective, an anti-interleukin-6 receptor monoclonal antibody may be an effective agent especially in the countries where anti-IL-1 therapy is not easily available. In this study, we reviewed the effect of tocilizumab (TCZ) on AOSD in Korean patients, retrospectively.

Methods: 24 AOSD patients were collected from 7 centers in Korea. The response to TCZ was defined as decreased modified Pouchot’s score more than 2 score with decreased acute phase reactants compared to initial treatment of TCZ at least two consecutive months. We used the one-way ANOVA (or Krusal-Wallis test) for continuous variable and chi-square test for trend for categorical variables.

Results:

Patients (18 women/6 men) had a mean age of 44.0 ± 18.4 years and the age of diagnosis was 37.4 ± 20.6 years old. The mean disease duration before TCZ treatment was 48.43 ± 43.7 months. Eleven patients (45.8%) had polycyclic systemic pattern and twelve patients (50.0%) had chronic articular pattern. One patient couldn’t be classified due to short disease duration.

Immune modulating agents before TCZ therapy were as follows: methotrexate (n=17), leflunomide (N=6), cyclosporine (n=4) and hydroxychloroquine (n=3). Biologic agents before TCZ therapy were etanercept (N=8), infliximab (n=6), adalimumab (n=4), abatacepts (n=2) and anakinra (n=1). At the time of TCZ treatment, the most frequent clinical manifestation was arthritis (79.2%). Rash (41.7%), fever (41.7%), myalgia (33.3%), and sore throat (20.8%) were accompanied. The baseline laboratory parameters such as leukocytosis, ESR, CRP and serum ferritin showed high level. The mean dosage of TCZ was 6.9 mg/kg (4-8 mg/kg) per 4 weeks and mean duration of TCZ administration was 8.4 ± 6.8 months. The majority of patients showed clinical or laboratory improvement after TCZ therapy. Although the dosage of prednisolone was reduced with clinical improvement at 6th month and 12th month, statistical significance was not showed (Table 1).

In 25.0 % of patients adverse events occurred during TCZ treatment as follows: leukopenia (n=1), gastrointestinal symptoms (n=2), infusion reaction (n=2), and pulmonary tuberculosis (n=1). Four patients (16.7%) relapsed after 5.0±3.6 months of discontinuation of TCZ.

Table 1. Change of clinical manifestations and laboratory parameters before and after TCZ treatment
	Baseline (N=24)	After 6 months (N=17)	After 12 months (N=11)
Fever*	10(41.7)	1(5.9)	1(9.1)
Sore throat	5(20.8)	1(5.9)	0(0.0)
Rash*	10(41.7)	2(11.8)	1(9.1)
Itching	7(29.2)	2(11.8)	1(9.1)
Myalgia**	8(33.3)	0(0.0)	0(0.0)
Arthralgia/arthritis	19(79.2)	11(64.7)	8(72.7)
Lymphadenopathy	2(8.3)	0(0.0)	0(0.0)
Splenomegaly	2(8.3)	1(5.9)	0(0.0)
Serositis	3(12.5)	0(0.0)	0(0.0)
Modified Pouchot’s Score, mean±SD	3.0 ± 1.9	1.3 ± 1.2	1.1 ± 0.7
Leukocytosis, mean±SD	14081.3 ± 6597.3	11810.0 ± 6712.8	12784.6 ± 6741.0
ESR (mm/hour), mean±SD**	64.7 ± 29.0	14.2 ± 20.0	23.6 ± 29.3
CRP (mg/dL), mean±SD*	5.0 ± 4.2	1.7 ± 2.8	4.6 ± 6.4
Ferritin (ng/mL), mean±SD	1440.2 ± 2027.3	374.3 ± 857.0	302.6 ± 340.0
Prednisolone dose (mg/day), mean±SD	15.4 ± 10.0	6.8 ± 4.4	7.8 ± 3.0
Values are the number (%), p < 0.05, *p < 0.005

Conclusion: TCZ was effective in Korean AOSD patients who were refractory to conventional therapy or other biologic agents. However, larger and prospective study is needed for further investigation.

Disclosure: S. T. Song, None; J. J. Kim, None; S. Lee, None; H. J. Jeong, None; I. W. Sohn, None; S. W. Lee, None; J. H. Lee, None; H. A. Kim, None; K. H. Lee, None; S. T. Choi, None; E. Y. Lee, None; K. Shin, None; H. S. Cha, None; D. H. Yoo, None.

To cite this abstract in AMA style:

Song ST, Kim JJ, Lee S, Jeong HJ, Sohn IW, Lee SW, Lee JH, Kim HA, Lee KH, Choi ST, Lee EY, Shin K, Cha HS, Yoo DH. Effect of Tocilizumab on Adults Onset Still’s Disease in Korean Population: Multicenter Retrospecitve Study of 24 Cases [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/effect-of-tocilizumab-on-adults-onset-stills-disease-in-korean-population-multicenter-retrospecitve-study-of-24-cases/. Accessed .

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