Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Kwon, Oh Chan; Choi, Wonho; Ahn, Soo Min; Oh, Ji Seon; Hong, Seokchan; Lee, Chang-Keun; Yoo, Bin; Park, Min-Chan; Kim, Yong-Gil

doi:10.1186/s42358-024-00368-w

Oh Chan Kwon

Data curation

Formal analysis

Investigation

Software

Visualization

Writing - original draft

Writing - review & editing

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, 06273 Seoul, Korea

† Oh Chan Kwon and Wonho Choi contributed equally as co-first authors in this study.

Wonho Choi

Data curation

Formal analysis

Investigation

Software

Visualization

Writing - review & editing

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

† Oh Chan Kwon and Wonho Choi contributed equally as co-first authors in this study.

Soo Min Ahn

Methodology

Validation

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

Ji Seon Oh

Methodology

Validation

read and approved the final manuscript.

Department of Biomedical Informatics, Asan Medical Center, Seoul, Korea

Seokchan Hong

Methodology

Validation

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

Chang-Keun Lee

Methodology

Validation

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

Bin Yoo

Methodology

Validation

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

Min-Chan Park ^** Correspondence: Min-Chan Park mcpark@yuhs.ac Yong-Gil Kim bestmd2000@amc.seoul.kr

Formal analysis

Investigation

Software

Visualization

Writing - review & editing

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, 06273 Seoul, Korea

https://orcid.org/0000-0003-1189-7637

Yong-Gil Kim ^** Correspondence: Min-Chan Park mcpark@yuhs.ac Yong-Gil Kim bestmd2000@amc.seoul.kr

Conceptualization

Park MC

Formal analysis

Funding acquisition

Investigation

Software

Visualization

Writing - review & editing

read and approved the final manuscript.

Division of Rheumatology, Department of Internal Medicine, College of Medicine, University of Ulsan, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, 05505 Seoul, Korea

* Correspondence: Min-Chan Park mcpark@yuhs.ac Yong-Gil Kim bestmd2000@amc.seoul.kr

†
Oh Chan Kwon and Wonho Choi contributed equally as co-first authors in this study.

Competing interests

Not applicable.

Characteristics	N = 32
Age, years, median (IQR)	56.5 (48.3, 61.0)
Female, n (%)	30 (93.8)
Disease duration, years, median (IQR)	13.5 (8.4, 21.5)
RF positive, n (%)	26 (81.3)
Anti-CCP Ab positive, n (%)^a a Patients (n = 5) with missing data excluded	23 (85.2)
Erosion on x-ray, n (%)	26 (81.3)
Number of bDMARDs prior to the first JAKi, median (IQR) First JAKi, n (%)	1.0 (0.0, 2.0)
Tofacitinib	30 (93.8)
Baricitinib	2 (6.3)
Duration of first JAKi exposure, months, median (IQR) Reason for discontinuation of first JAKi, n (%)	8.0 (3.5, 17.0)
Primary failure	16 (50.0)
Secondary failure	6 (18.8)
Adverse events	10 (31.3)
Number of bDMARDs between JAKis, median (IQR)	1.0 (1.0, 2.0)
Interval between JAKis, months, median (IQR) Second JAKi, n (%)	10.0 (3.0, 22.0)
Tofacitinib	2 (6.3)
Baricitinib	29 (90.6)
Upadacitinib Concomitant medication	1 (3.1)
Methotrexate, n (%)	22 (68.8)
Methotrexate dose, mg/week, median (IQR)	10.0 (9.4–13.1)
Glucocorticoid, mg/day^b b mg/day of prednisolone or its equivalent , median (IQR)	5.0 (0.0, 5.0)

	N = 32
Duration of the second JAKi exposure, months, median (IQR)	13.5
	(4.5,
	23.8)
Discontinuation of the second JAKi, n (%)	20
	(62.5)
Time to discontinuation of the second JAKi, months, median	9.0 (3.3,
(IQR)	13.8)
Reasons for discontinuation of the second JAKi, n (%)
Primary failure	9 (45.0)
Secondary failure	5 (25.0)
Adverse events	2 (10.0)
Insurance coverage issues	4 (20.0)

	Baseline	6-month	Pvalue^a a The P value of Wilcoxon signed rank test, which included 27 patients who had their disease activity assessed at both baseline and 6-month
Number of patients at assessment, n (%)	32 (100.0)	27 (84.4)	N/A
TJC	10.0 (6.0, 18.0)	0.0 (0.0, 2.0)	< 0.001
SJC	6.0 (4.0, 12.0)	0.0 (0.0, 0.0)	< 0.001
VAS	85.0 (80.0, 90.0)	30.0 (30.0, 30.0)	< 0.001
ESR, mm/h	52.0 (12.0, 69.0)	30.0 (24.0, 46.0)	0.100
CRP, mg/dL	1.01 (0.10, 2.68)	0.38 (0.13, 1.23)	0.026
DAS28-ESR	5.84 (5.41, 6.30)	3.28 (2.81, 3.89)	< 0.001
DAS28-CRP	5.48 (4.75, 5.94)	2.34 (1.78, 3.10)	< 0.001

Patients (Age/Sex)	First JAKi		Second JAKi
Patients (Age/Sex)	Drug	Reasons for discontinuation	Drug	Reasons for discontinuation
#1 (63/F)	Tofacitinib	Primary failure	Baricitinib	Secondary failure
#2 (62/F)	Tofacitinib	Primary failure	Baricitinib	Secondary failure
#3 (48/F)	Tofacitinib	Primary failure	Baricitinib	Adverse event
#4 (45/F)	Tofacitinib	Primary failure	Upadacitinib	N/A^a a Not applicable because the JAKi was continued
#5 (40/F)	Tofacitinib	Secondary failure	Baricitinib	Primary failure
#6 (61/F)	Tofacitinib	Secondary failure	Baricitinib	Primary failure
#7 (58/F)	Tofacitinib	Primary failure	Baricitinib	Primary failure
#8 (66/M)	Tofacitinib	Secondary failure	Baricitinib	Secondary failure
#9 (49/F)	Tofacitinib	Primary failure	Baricitinib	Primary failure
#10 (56/F)	Tofacitinib	Primary failure	Baricitinib	Primary failure
#11 (59/F)	Tofacitinib	Primary failure	Baricitinib	Primary failure
#12 (60/M)	Tofacitinib	Primary failure	Baricitinib	Secondary failure
#13 (68/F)	Tofacitinib	Secondary failure	Baricitinib	Adverse event
#14 (55/F)	Tofacitinib	Secondary failure	Baricitinib	Insurance coverage issue
#15 (35/F)	Tofacitinib	Primary failure	Baricitinib	Insurance coverage issue
#16 (50/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#17 (49/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#18 (49/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#19 (58/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#20 (35/F)	Tofacitinib	Secondary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#21 (58/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#22 (65/F)	Tofacitinib	Primary failure	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#23 (40/F)	Tofacitinib	Adverse event	Baricitinib	Primary failure
#24 (57/F)	Tofacitinib	Adverse event	Baricitinib	Secondary failure
#25 (56/F)	Tofacitinib	Adverse event	Baricitinib	Primary failure
#26 (35/F)	Tofacitinib	Adverse event	Baricitinib	Primary failure
#27 (68/F)	Tofacitinib	Adverse event	Baricitinib	Insurance coverage issue
#28 (34/F)	Baricitinib	Adverse event	Tofacitinib	Insurance coverage issue
#29 (54/F)	Tofacitinib	Adverse event	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#30 (57/F)	Tofacitinib	Adverse event	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#31 (62/F)	Tofacitinib	Adverse event	Baricitinib	N/A^a a Not applicable because the JAKi was continued
#32 (61/F)	Baricitinib	Adverse event	Tofacitinib	N/A^a a Not applicable because the JAKi was continued

[1] * Correspondence: Min-Chan Park mcpark@yuhs.ac Yong-Gil Kim bestmd2000@amc.seoul.kr

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Drug survival and change of disease activity using a second janus kinase inhibitor in patients with difficult-to-treat rheumatoid arthritis who failed to a janus kinase inhibitor and subsequent biologics

Abstract

Background

Methods

Results

Conclusions