Clinical trial NCT06114407: Baricitinib in the Treatment of Refractory Axial Spondyloarthritis Patients: A Comparison With Tofacitinib
Official title: Baricitinib in the Treatment of Refractory Axial Spondyloarthritis Patients: A Comparison With Tofacitinib
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Spondyloarthritis, Axial
Keywords: Spondyloarthritis
Tofacitinib
Baricitinib
Refractory
Axial
Lead sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Sponsor class: OTHER
Collaborators: name: Healthcare Pharmaceuticals
First posted: 2023-11-02
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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?

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.

Eligibility criteria: 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

Primary outcomes:
measure: Ankylosing Spondylitis Disease Activity Score-C Reative Protein ( ASDAS-CRP)
timeFrame: ASDAS CRP will be assessed at baseline, 4th and 12th week
Secondary outcomes:
measure: Ankylosing Spondylitis Disease Activity Score-ESR ( ASDAS-ESR)
timeFrame: ASDAS ESR will be assessed at baseline, 4th and 12th week
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
timeFrame: BASDAI will be assessed at baseline, 4th and 12th week
measure: Bath Ankylosing Spondylitis Functional Index (BASFI)
timeFrame: BASFI will be assessed at baseline, 4th and 12th week
measure: Bath Ankylosing Spondylitis Metrology Index (BASMI)
timeFrame: BASMI will be assessed at baseline, 4th and 12th week
measure: Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)
timeFrame: MASES will be assessed at baseline, 4th and 12th week
measure: Ankylosing Spondylitis Quality of Life Questionnaire(ASQoL)
timeFrame: ASQoL will be assessed at baseline, 4th and 12th week
Other outcomes:
measure: Health Assessment questionnaire Disability Index (HAQ-DI)
timeFrame: HAQ-DI will be assessed at baseline, 4th and 12th week
measure: 36-Item Short Form Survey ( SF-36)
timeFrame: SF-36 will be assessed at baseline, 4th and 12th week
Locations:
city: Dhaka
country: Bangladesh
facility: Bangabandhu Sheikh Mujib Medical University
Study officials:
affiliation: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
name: Samaresh Das, M B B S
role: PRINCIPAL_INVESTIGATOR
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