Baricitinib in the Treatment of Refractory Axial Spondyloarthritis Patients: A Comparison With Tofacitinib

December 16, 2023 updated by: Samaresh Das, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Axial Spondylarthritis (ax-SpA) is an important cause of inflammatory back pain in young adults. Janus kinase inhibitors (JAKi) has been approved for treatment of ax-SpA. Tofacitinib and baricitinib are drugs from same family (JAKi). Baricitinib is relatively less expensive than Tofacitinib.

The goal of this non-inferiority clinical trial is to learn about the efficacy of baricitinib in refractory axial spondyloarthritis ( ax-SpA) and to compare its effect with that of tofacitinib. The main questions it aims to answer are:

  1. Is baricitinib 4 mg effective in refractory ax-SpA?
  2. Is baricitinib non-inferior to tofacitinib in refractory ax-SpA? Participants (treatment group, 92 patients) will be treated with baricitinib 2 mg twice daily for 12 weeks. Ninety two patients getting tofacitinib 10 mg/day (comparison group) will be taken as historical control from another study on the efficacy of tofacitinib in refractory ax-SpA?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This clinical trial will be conducted in the department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from October 2023-March 2025. A total of 184 patients of both genders (age ≥18 years) with refractory ax-SpA meeting the inclusion and exclusion criteria will be enrolled in this study after having informed written consent. There will be two groups with 92 patients in each group. Treatment group (92 patients) will get baricitinib 4 mg daily. Ninety two patients getting tofacitinib 10 mg/day (control arm) will be taken as historical control from another ongoing study in this department. Patients of refractory ax-SpA with high disease activity (ASDAS-CRP≥2.1) will be the entry criteria in this study.

At baseline CBC, ESR, CRP, SGPT, Serum creatinine and X-ray SI joint (A/P view), HLA-B27(if needed), CXR P/A view and MT test, fasting lipid profile will be done. Baricitinib will be given to patients free of cost. Drug adherence will be ensured by monthly pill count. Follow up visit will be done at 4th and 12th week. At each follow up patients will be evaluated clinically, relevant laboratory test and will be assessed for any side effects. All the findings will be noted in a semi-structure questionnaire. At 12th week patients will be evaluated for efficacy. Outcome will be assessed by ASDAS CRP and a change of ≥ 1.1 units from baseline for clinically important improvement and≥ 2.0 units for major improvement. Disease activity will also be assessed by ASDAS-ESR, BASDAI, functional assessment by BASFI, spinal mobility by BASMI, pain, stiffness and patient global assessment by NRS, enthesitis byMASES, quality of life by Bangla version of SF-36, Bangla version of HAQ-DI and pilot Bangla version of ASQoL. Chi-square test will used for analysis of categorical variables. Comparison of the two groups will be done using independent t-test when the data are in normal distribution and Man-Whitney U test in case of skewed distribution. At 95% confidence interval P value < 0.05 will be considered statistically significant.

Each patient will be informed about the nature and purpose of the study. This study will be free from any undue benefits or influences. If any serious adverse events develop, drugs will be stopped and the patients will be treated with utmost care. Privacy, anonymity and confidentiality of every patient will be maintained in every step. Every patient will have the rights to participate and withdraw from the study at any point of time. The withdrawal of the patients will not alter their deserved medical care. Ethical clearance will be taken from Institutional Review Board (IRB) of BSMMU.

If baricitinib is found effective in refractory ax-SpA, it will decrease the treatment cost of the patients.

Study Type

Interventional

Enrollment (Estimated)

184

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Bangladesh
      • Dhaka, Bangladesh, 1000
        • Recruiting
        • Bangabandhu Sheikh Mujib Medical University
        • Contact:
        • Principal Investigator:
          • Samaresh Das, M B B S

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Patients meeting the ASAS classification criteria for axial spondyloarthritis
  3. Patients fulfilling the definition of refractory axial spondyloarthritis
  4. Patients with ASDAS-CRP ≥ 2.1

Exclusion Criteria:

  1. Patients who are currently on treatment or had been previously treated with bDMARDs or tsDMARDS (including JAK inhibitors)
  2. Hemoglobin < 9 gm/dl
  3. WBC count < 4000/cmm, Neutrophil count < 1000 cmm, Platelet count < 100000/cmm
  4. Any current or previous history of serious opportunistic infection including tuberculosis
  5. Live vaccine within 3 months prior to the first dose
  6. GFR < 50 ml/min
  7. ALT > 2 times upper limit normal
  8. Pregnancy, breastfeeding or women of reproductive age group not using effective contraceptive
  9. Current or previous history of malignancy, lymphoproliferative disease
  10. New York Heart Association Class III and IV congestive heart failure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Baricitinib
Participants of 'Baricitinib' arm will be treated with tablet baricitinib 2 mg twice daily for 12 weeks
Drug: Baricitinib 2mg
Participants of arm 'A' will be treated with tablet baricitinib 2 mg twice daily for 12 weeks
Other Names:
  • Baritinib 2 mg
Active Comparator: Tofacitinib
Participants of 'Tofacininib' arm getting tablet tofacitinib 5 mg twice daily for 12 weeks will be taken as historical control arm from another study on the efficacy of tofacitinib in refractory axial spondyloarthritis
Drug: Tofacitinib 5 mg
Participants of arm 'B' getting tablet tofacitinib 5 mg twice daily for 12 weeks will be taken as historical control arm from another study on the efficacy of tofacitinib in refractory axial spondyloarthritis
Other Names:
  • Tofacent 5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ankylosing Spondylitis Disease Activity Score-C Reative Protein ( ASDAS-CRP)
Time Frame: ASDAS CRP will be assessed at baseline, 4th and 12th week

To calculate ASDAS-CRP, besides the value of CRP, the four other items are back pain duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity (these are assessed by 0-10cm, visual analogue scale [VAS] or 0-10, numerical rating scale [NRS]).

Four disease activity states were categorized by ASAS: "inactive disease", "moderate disease activity", "high disease activity" and "very high disease activity".The 3 cut-offs chosen to separate these states are: <1.3 "inactive disease", 1.3 to <2.1 "low disease activity", 2.1 to <3.5 "high disease activity" and >3.5 "very high disease activity".

Patients of refractory ax-SpA with high disease activity (ASDAS-CRP≥2.1) will be the entry criteria in this study.

Primary outcome will be assessed by ASDAS CRP and a change of ≥ 1.1 units from baseline for clinically important improvement and ≥ 2.0 units for major improvement.
ASDAS CRP will be assessed at baseline, 4th and 12th week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ankylosing Spondylitis Disease Activity Score-ESR ( ASDAS-ESR)
Time Frame: ASDAS ESR will be assessed at baseline, 4th and 12th week

To calculate ASDAS-ESR, besides the value of ESR (mm/hr), the four other items are back pain duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity (these are assessed by 0-10cm, visual analogue scale [VAS] or 0-10, numerical rating scale [NRS]).

Four disease activity states were categorized by ASAS: "inactive disease", "moderate disease activity", "high disease activity" and "very high disease activity".The 3 cut-offs chosen to separate these states are: <1.3 "inactive disease", 1.3 to <2.1 "low disease activity", 2.1 to <3.5 "high disease activity" and >3.5 "very high disease activity".

Outcome will be assessed by ASDAS ESR and a change of ≥ 1.1 units from baseline for clinically important improvement and ≥ 2.0 units for major improvement.
ASDAS ESR will be assessed at baseline, 4th and 12th week
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Time Frame: BASDAI will be assessed at baseline, 4th and 12th week
The BASDAI consists of a 01 through 10 scale (01 being no problem and 10 being worst problem) which is used to answer 6 questions pertaining to 5 major symptoms of AS: Fatigue, spinal pain, joint pain/ swelling, areas of localized tenderness ( also called enthesitis or inflammation of tendons or ligaments), morning stiffness duration, morning stiffness severity. The index results a final 0-10 BASDAI score.
BASDAI will be assessed at baseline, 4th and 12th week
Bath Ankylosing Spondylitis Functional Index (BASFI)
Time Frame: BASFI will be assessed at baseline, 4th and 12th week

BASFI scores 10 items

  1. Putting on your socks or tights without help or aids (eg, sock aid).
  2. Bending forward from the waist to pick up a pen from the floor without an aid.
  3. Reaching up to a high shelf without help or aids (eg, helping hand).
  4. Getting up out of an armless dining room chair without using your hands or any other help.
  5. Getting up off the floor without help from lying on your back.
  6. Standing unsupported for 10 min without discomfort.
  7. Climbing 12 to 15 steps without using a handrail or walking aid. One foot at each step.
  8. Looking over your shoulder without turning your body.
  9. Doing physically demanding activities (eg, physiotherapy, exercises, gardening or sports).
  10. Doing a full day's activities, whether it be at home or at work. The BASFI is the mean of 10 item scores completed on a numerical rating scale. A Bangla validated version of BASFI will used in this study.
BASFI will be assessed at baseline, 4th and 12th week
Bath Ankylosing Spondylitis Metrology Index (BASMI)
Time Frame: BASMI will be assessed at baseline, 4th and 12th week

BASMI includes five clinical measurements that reflect axial mobility:

  1. tragus to wall
  2. lumbar flexion
  3. cervical rotation
  4. lumbar side flexion
  5. intermalleolar distance.

Grading 0-10 or linear function. Total score 0-10.
BASMI will be assessed at baseline, 4th and 12th week
Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
Time Frame: MASES will be assessed at baseline, 4th and 12th week

MASES includes enthesitis at 13 Sites:

  • Costochondral 1 right/left
  • Costochondral 7 right/left
  • Spina iliaca anterior superior right/left
  • Crista iliaca right/left
  • Spina iliaca posterior right/left
  • Processus spinosus L5
  • Achilles tendon, proximal insertion right/left. No grading All sites are scored as 0 or 1 The MASES is the sum of all site scores (from 0 to 13).
MASES will be assessed at baseline, 4th and 12th week
Ankylosing Spondylitis Quality of Life Questionnaire(ASQoL)
Time Frame: ASQoL will be assessed at baseline, 4th and 12th week

ASQoL includes 18 questions with response 'Yes' or 'No' scoring 01 or 0 respectively.

  1. My condition limits the places I can go
  2. I sometimes feel like crying
  3. I have difficulty dressing
  4. I struggle to do jobs around the house
  5. It's impossible to sleep
  6. I am unable to join in activities with my friends/family
  7. I am tired all the time
  8. I have to keep stopping what I am doing to rest
  9. I have unbearable pain
  10. It takes a long time to get going in the morning
  11. I am unable to do jobs around the house
  12. I get tired easily
  13. I often get frustrated
  14. The pain is always there
  15. I feel I miss out on a lot
  16. I find it difficult to wash my hair
  17. My condition gets me down
  18. I worry about letting people down All item scores are added to give a total score. Scores can range from 0 (good QoL) to 18 (poor QoL).

A Bangla version of ASQoL will be used in this study.
ASQoL will be assessed at baseline, 4th and 12th week

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health Assessment questionnaire Disability Index (HAQ-DI)
Time Frame: HAQ-DI will be assessed at baseline, 4th and 12th week

HAQ-DI includes 8 categories with 20 questions about physical abilities

  1. Dressing and Grooming
  2. Arising
  3. Eating
  4. Walking
  5. Hygiene
  6. Reach
  7. Grip
  8. Activities Each category includes aids or devices or help from another person. The higher score in each category is counted. Sum of the scores are divided by 8. A Bangla validated version of HAQ-DI will be used in this study.
HAQ-DI will be assessed at baseline, 4th and 12th week
36-Item Short Form Survey ( SF-36)
Time Frame: SF-36 will be assessed at baseline, 4th and 12th week
SF-36 measures health related quality of life covering 8 domains of health including physical functioning, physical role, pain, general health, vitality, social function, emotional role, and mental health.
SF-36 will be assessed at baseline, 4th and 12th week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Collaborators

Healthcare Pharmaceuticals

Investigators

  • Principal Investigator: Samaresh Das, M B B S, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2023

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

October 28, 2023

First Submitted That Met QC Criteria

November 1, 2023

First Posted (Actual)

November 2, 2023

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 16, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4548

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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