UMIN-CTR Clinical Trial

Public title

Clinical study on drug holiday with regulated rheumatoid arthritis activity after treatment with tofacitinib (Xanadu study)

Acronym

Clinical study on rheumatoid arthritis treated with tofacitinib

Scientific Title

Clinical study on drug holiday with regulated rheumatoid arthritis activity after treatment with tofacitinib (Xanadu study)

Scientific Title:Acronym

Clinical study on rheumatoid arthritis treated with tofacitinib

Region

Japan

Condition

Rheumatoid arthritis

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Evaluate the effect of tofacitinib discontinuation on relapse and joint destruction in rheumatoid arthritis after preserved disease control.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Primary outcomes

SDAI remission, low disease activity rate
DS28 remission rate, low disease activity rate

Key secondary outcomes

RF, MMP-3, CRP, ACPA, HAQ, Sharp score, adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

3

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Continue current treatment

Interventions/Control_2

Tofacitinib discontinuation

Interventions/Control_3

MTX discontinuation

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

All patients that qualify the criteria below would be a candidate;
1) Rheumatoid arthritis was diagnosed following the 1987 or 2010 criteria
2) Rheumatoid arthritis patients treated with tofacitinib and SDAI<3.3 was observed at least 2 points (week-24 and -48) and is over 18 years old.

Key exclusion criteria

Patients judged as inadequate by the subinvestigator

Target sample size

400

Name of lead principal investigator

1st name
Middle name
Last name	Yoshiya Tanaka

Organization

School of Medicine, University of Occupational and Environmental Health, Japan

Division name

First Department of Internal Medicine

Zip code

Address

1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan

TEL

093-603-1611

Email

tanaka@med.uoeh-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Satoshi Kubo

Organization

School of Medicine, University of Occupational and Environmental Health, Japan

Division name

First Department of Internal Medicine

Zip code

Address

1-1, Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan

TEL

093-603-1611

Homepage URL

Email

kubosato@med.uoeh-u.ac.jp

Institute

School of Medicine, University of Occupational and Environmental Health, Japan

Institute

Department

Personal name

Organization

none

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2014

Year

10

Month

17

Day

URL releasing protocol

https://rmdopen.bmj.com/content/9/2/e003029

Publication of results

Published

URL related to results and publications

https://rmdopen.bmj.com/content/9/2/e003029

Number of participants that the trial has enrolled

113

Results

A total of 48 patients achieved remission at week 52. After discontinuation of tofacitinib, only 29.2% of patients remained remission, while 50.0% of patients sustained remission after MTX discontinuation. A greater proportion of bio-naive patients achieved remission at week 52 and sustained LDA with tofacitinib discontinuation at week 104. The patients who were able to discontinue tofacitinib without flares had lower rheumatoid factor and lower anti CCP antibody before discontinuation of tofacitinib.

Results date posted

2023

Year

05

Month

03

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

One hundred and thirteen patients who had inadequate responses to MTX (MTX-IR) with or without bDMARDs were enrolled in this study. In summary, 113 patients were first randomised into two strategies: 56 patients in the discontinuation of tofacitinib and 57 patients in the discontinuation of MTX. All patients were then treated with tofacitinib in combination with MTX. The results of the randomisation were blinded to both the investigator and the patients until week 52. The mean age of the patients was 58 for those in the discontinuation of the tofacitinib group and 57 years for those in the discontinuation of the MTX group. Seventy-one per cent and 63% of the patients in each respective group had failed at least one biological agent. The mean disease activity at baseline was 23.9 and 22.9 for CDAI, respectively. The baseline characteristics of the two groups were statistically comparable except for RF and ACPA positivity.

Participant flow

All patients inadequately responded to background MTX with or without bDMARDs and were randomly assigned to one of two groups: the tofacitinib discontinuation group and the MTX discontinuation group at baseline. After randomisation, tofacitinib was administered in addition to MTX in all the patients of both groups. At week 52, either tofacitinib or MTX was discontinued according to the assignments if a patient achieved sustained clinical remission as defined by CDAI. Patients who did not reach clinical remission at week 52 did not move to the next step. Patients from both groups were allowed to visit the outpatient clinic every month and had to visit for the periodical follow-up (weeks 56, 64, 78 and 90) to check for disease activity until week 104. Patients with flares in the tofacitinib or MTX discontinuation groups were re-administered tofacitinib or MTX, respectively.

Adverse events

Before discontinuation of tofacitinib or MTX at week 52, a total of 8 (out of 113) SAEs leading to withdrawal from the study occurred (Shingles, Appetite loss 2, lymphoma, Pancreatic cancer, Oral aphtha, General fatigue, Eruption). After discontinuation of tofacitinib or MTX, no SAEs were recorded in both groups.

Outcome measures

The primary endpoint of the XANADU study was the proportion of patients who sustained clinical remission at week 104. Tender joint counts, swelling joint counts, patients' global assessment, evaluator's global assessment, C reactive protein and erythrocyte sedimentation rate were recorded. Disease flares are defined based on moderate or high disease activity, according to CDAI. Subjects who experienced flares were re-administered either tofacitinib or MTX.
The secondary endpoints were the proportion of patients who sustained low disease activity at week 104, the proportion of patients who had SAEs throughout the study, and the proportion of patients who achieved clinical remission after rescue by re-administration of tofacitinib or MTX. Subgroup exploratory analyses were performed to reveal which patients could achieve successful drug discontinuation.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2014

Year

05

Month

01

Day

Date of IRB

2014

Year

05

Month

01

Day

Anticipated trial start date

2014

Year

10

Month

01

Day

Last follow-up date

2022

Year

02

Month

28

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

10

Month

17

Day

Last modified on

2023

Year

05

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017779