Cessation of Biologic Treatment in Patients With Takayasu Arteritis in Sustained Remission
Phase: NA
Conditions: Takayasu Arteritis
Sponsor: Marmara University

STUDY PROTOCOL 
 
Official Title: 
 
Cessation of Biologic Treatment in Patients With Takayasu Arteritis in Sustained Remission 
 
ClinicalTrials.gov Identifier: 
 
NCT Pending 
 
Document Date: 
 
18 March 2026 

Principal Investigator 
Fatma Alibaz-Oner, MD 
Division of Rheumatology 
Marmara University School of Medicine 
Istanbul, Türkiye 
Study Center 
Marmara University Pendik Training and Research Hospital 
Division of Rheumatology 
Istanbul, Türkiye 
Protocol Version 
Version 1.0 
Ethics Committee Approval 
Marmara University Faculty of Medicine 
Clinical Research Ethics Committee 
Approval Number: 09.2024.1469 
 
 
 
 
Background 
and Rationale 
Takayasu arteritis (TAK) is a rare, chronic granulomatous large-vessel arteritis affecting 
mainly aorta and its major branches. In addition to glucocorticoids, non-biologic agents 
such as methotrexate, azathioprine, and mycophenolate mofetil can be chosen in the 
treatment. However, prospective and retrospective studies have shown the efficacy of 
biologic agents in refractory and relapsing patients. Treatment choices are typically 
guided by observational studies and expert opinions, yet there is a notable lack of 
literature providing recommendations on when it is safe to discontinue treatment. 
In a review assessing the efficacy of tocilizumab in patients with Takayasu 
arteritis, it was found that six out of 13 patients (46%) who received tocilizumab 
for a median duration of six months experienced a relapse after a median of five 
months (range: 2-9) following the discontinuation of treatment. The study 
indicated that the duration of tocilizumab therapy was comparable between 
relapsing and non-relapsing patients1. Additionally, in a separate study 
comparing anti-TNF agents and tocilizumab in Takayasu arteritis patients, 
biologic treatments were discontinued in seven patients (comprising four on 
infliximab, two on tocilizumab, and one on adalimumab) upon achieving 
permanent remission. Among these, one patient (50%) from the tocilizumab 

                                                     
1 Decker vd., “Tocilizumab and Refractory Takayasu Disease”. 
2 Alibaz-Oner vd., “Biologic Treatments in Takayasu’s Arteritis”. 
3 Stone vd., “Long-Term Effect of Tocilizumab in Patients with Giant Cell Arteritis”. 
4 Smolen vd., “EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and 
Biologic Disease-Modifying Antirheumatic Drugs”. 
5 Ramiro vd., “ASAS-EULAR Recommendations for the Management of Axial Spondyloarthritis”. 
group relapsed 26 months after treatment cessation, while three patients (60%) 
from the anti-TNF group relapsed after a median of 18 months (range: 7-60) 
following discontinuation2. 
When examining other inflammatory diseases treated with biologic agents, the 
GiACTA study on giant cell arteritis found that a significant number of patients 
who received tocilizumab for one year were able to maintain drug-free remission 
for two years after stopping the treatment3. In contrast, for rheumatoid arthritis, 
discontinuing biologic disease-modifying anti-rheumatic drugs (bDMARDs) 
and/or conventional synthetic disease-modifying anti-rheumatic drugs 
(csDMARDs) in patients who have been in remission for six months or more 
after tapering off glucocorticoids often leads to exacerbations. Therefore, it is 
usually advisable to consider either a dose reduction or an increase in the 
interval between doses4. Similarly, for ankylosing spondylitis, it is recommended 
to develop a treatment plan that includes a reduction in bDMARD doses to 
effectively maintain treatment responses in patients who have been in remission 
for at least six months5. 
Study 
Duration 
Dose tapering period: 3 months; Post-withdrawal follow-up period: 12 months 
 
Study Design This is a prospective, observational cohort study designed to evaluate the outcomes of 
biologic treatment withdrawal in patients with Takayasu arteritis who have received 
TNF inhibitors or tocilizumab for at least 3 years and are in long-standing clinical and 
radiologic remission. 
Eligible patients will undergo a 3-month biologic dose tapering period. Patients who do 
not experience a relapse during this phase will discontinue biologic therapy at the end of 
3 months. All patients will then enter a 12-month post-withdrawal follow-up period. 
Clinical and laboratory evaluations will be conducted at 1 month following cessation 
and every 3 months thereafter.  
Prior to tapering, carotid and thoracoabdominal CT or MR angiography will be 
performed in patients who have not undergone vascular imaging within the previous 12 
months. In case of clinical suspicion, re-imaging is planned at the discretion of the 
physician. Active disease and major/minor relapse evaluation of patients is planned to 
be performed according to the ‘EULAR 2018 Large Vessel Vasculitis (LVV) Treatment 
Recommendations’ consensus report. 

Primary 
Objective 
To evaluate whether patients with Takayasu arteritis who have been in long-
standing clinical and radiologic remission and have received biologic therapy 
(TNF inhibitors or tocilizumab) for at least 3 years can maintain remission 
following planned treatment discontinuation 
Primary 
outcome 
 
The proportion of patients maintaining remission at month 12 following 
treatment withdrawal 
Secondary 
Objective 
 
The proportion of patients experiencing disease relapse (major or minor) 
during the 3-month dose tapering phase or the 12-month post-treatment 
withdrawal period 
 
The time to first disease relapse (major or minor) following biologic treatment 
withdrawal 
Primary and 
Secondary 
Outcome 
Measures 
Remission: The absence of new or worsening clinical symptoms and signs 
together with acute phase response within normal limits.  
Active disease: 
1. The presence of typical signs or symptoms of active LVV  
2. At least one of the following: 
1. Current activity on imaging or biopsy 
2. Ischaemic complications attributed to LVV 
3. Persistently elevated inflammatory markers (after other causes have been 
excluded) 
Major relapse: 
Recurrence of active disease with either of the following: 
1. Clinical features of ischaemia (including jaw claudication, visual 
symptoms, visual loss attributable to GCA, scalp necrosis, stroke, limb 
claudication) 
2. Evidence of active aortic inflammation resulting in progressive aortic or 
large vessel dilatation, stenosis or dissection. 
Minor relapse: 
Recurrence of active disease, not fulfilling the criteria for a major relapse 
Eligibility 
Criteria 
 
Participants must meet all of the following criteria to be eligible for 
enrollment: 
 

1. Diagnosis of TAK  according to the 2022 American College of 
Rheumatology/EULAR Classification Criteria for Takayasu Arteritis 
2. To have received biologic therapy (TNF inhibitors and/or tocilizumab) for at least 3 
years 
3. There is no evidence of activation in clinical evaluation, current vascular imaging and 
laboratory values 
4. Patients who have had no change in treatment in the last 1 year and who have not 
received glucocorticoid treatment in the last 6 months will be included 
5. Willing and able to provide written informed consent 
Exclusion 
Criteria 
 
1. Presence of additional diseases (inflammatory bowel disease, ankylosing 
spondylitis, etc.) in the active period that require the use of biologic agents 
2. Patients who cannot attend the planned control visits after dose reduction 
and treatment discontinuation 
3. Pregnancy or planning to become pregnant during the study period 
Treatment 
Description 
 
Eligible patients with Takayasu arteritis who have received biologic therapy (TNF 
inhibitors or tocilizumab) for at least 3 years and are in sustained clinical and 
imaging remission will undergo a predefined dose tapering protocol over a 3-
month period. The dose reduction schedules are as follows: 
 
Treatment dose reduction protocol; 
- Infliximab 3 mg/kg/6-8 w iv (according to previous dose range) 
- Adalimumab 40 mg sc/3 w 
- Certolizumab pegol 200 mg sc/3 w 
- Tocilizumab 162 mg sc/2 w 
-Tocilizumab 8 mg/kg iv/6 w 
 
Patients who do not relapse during the dose tapering phase will have biologic 
treatment discontinued completely at the end of 3 months. 
 
csDMARDs (e.g., methotrexate, azathioprine, mycophenolate mofetil) may be 
continued if stable for at least 12 months prior to tapering. 

 
 
 
 
 
 
Statistical 
analysis 
Descriptive statistics will be used to summarize baseline demographic and clinical 
characteristics. The primary outcome—the proportion of patients maintaining remission 
at month 12 following treatment withdrawal—will be analyzed using the Kaplan-Meier 
method to estimate remission maintenance over time. The corresponding 95% 
confidence interval will be calculated. 
Secondary outcomes, including the rate and timing of major and minor relapses during 
the dose tapering and 12-month post-withdrawal periods, will be evaluated using 
survival analysis techniques. Time-to-event data will be compared using the log-rank 
test where applicable. Cox proportional hazards regression models may be used to 
assess the impact of baseline variables on relapse risk. 
Subgroup analyses will be performed based on biologic agent type (e.g., TNFi vs 
tocilizumab) and concomitant DMARD use. A p-value < 0.05 will be considered 
statistically significant. 
Ethical 
Considerations 
The study will be conducted in accordance with the Declaration of Helsinki. Written 
informed consent will be obtained from all participants. Ethics committee approval was 
obtained from the Marmara University Faculty of Medicine Clinical Research Ethics 
Committee prior to patient enrollment (Approval No: 09.2023.1564).