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

Study Overview
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Brief Summary
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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: Is baricitinib 4 mg effective in refractory ax-SpA? 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
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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.

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

Conditions
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Spondyloarthritis, Axial

Intervention / Treatment
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* Drug: Baricitinib 2mg
* Drug: Tofacitinib 5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Patients meeting the ASAS classification criteria for axial spondyloarthritis Patients fulfilling the definition of refractory axial spondyloarthritis Patients with ASDAS-CRP ≥ 2.1 Exclusion Criteria: Patients who are currently on treatment or had been previously treated with bDMARDs or tsDMARDS (including JAK inhibitors) Hemoglobin < 9 gm/dl WBC count < 4000/cmm, Neutrophil count < 1000 cmm, Platelet count < 100000/cmm Any current or previous history of serious opportunistic infection including tuberculosis Live vaccine within 3 months prior to the first dose GFR < 50 ml/min ALT > 2 times upper limit normal Pregnancy, breastfeeding or women of reproductive age group not using effective contraceptive Current or previous history of malignancy, lymphoproliferative disease New York Heart Association Class III and IV congestive heart failure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib<br>Participants of 'Baricitinib' arm will be treated with tablet baricitinib 2 mg twice daily for 12 weeks | Drug: Baricitinib 2mg<br>* Participants of arm 'A' will be treated with tablet baricitinib 2 mg twice daily for 12 weeks<br>* Other names: Baritinib 2 mg;|
| Active Comparator: Tofacitinib<br>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<br>* 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<br>* Other names: Tofacent 5 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankylosing Spondylitis Disease Activity Score-C Reative Protein ( ASDAS-CRP) | 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) | 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) | 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) | BASFI scores 10 items Putting on your socks or tights without help or aids (eg, sock aid). Bending forward from the waist to pick up a pen from the floor without an aid. Reaching up to a high shelf without help or aids (eg, helping hand). Getting up out of an armless dining room chair without using your hands or any other help. Getting up off the floor without help from lying on your back. Standing unsupported for 10 min without discomfort. Climbing 12 to 15 steps without using a handrail or walking aid. One foot at each step. Looking over your shoulder without turning your body. Doing physically demanding activities (eg, physiotherapy, exercises, gardening or sports). 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) | BASMI includes five clinical measurements that reflect axial mobility: tragus to wall lumbar flexion cervical rotation lumbar side flexion 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) | 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) | ASQoL includes 18 questions with response 'Yes' or 'No' scoring 01 or 0 respectively. My condition limits the places I can go I sometimes feel like crying I have difficulty dressing I struggle to do jobs around the house It's impossible to sleep I am unable to join in activities with my friends/family I am tired all the time I have to keep stopping what I am doing to rest I have unbearable pain It takes a long time to get going in the morning I am unable to do jobs around the house I get tired easily I often get frustrated The pain is always there I feel I miss out on a lot I find it difficult to wash my hair My condition gets me down 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spondyloarthritis, Tofacitinib, Baricitinib, Refractory, Axial