Tofacitinib in the Treatment of Refractory Axial Spondyloarthritis Patients: A Dose Escalation Study

The goal of this clinical trial is to assess the efficacy of tofacitinib in refractory axial spodyloarthritis (ax-SpA) with dose escalation from 10mg to 15mg. Patients will start on 10mg and then divided into 2 groups (10 and 15) at 3rd month according to major improvement criteria.

The main question[s] it aims to answer are:

• Efficacy and safety of tofacitinib in different doses
• If escalation of tofacitinib is justified if clinical criteria is not fulfilled at 10mg

Study Overview

• Status: Completed
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Drug: Tofacitinib

Detailed Description

Axial spondyloarthritis (ax-SpA) is a major cause of chronic low back pain in the young. It causes significant disability and impairs quality of life. Management of (ax-SpA) includes physical therapy along with NSAIDs, followed by TNFi or IL-17i or JAKi in refractory ax-SpA. In Bangladesh, TNFi and IL-17i are expensive, whereas Tofacitinib (JAKi) is affordable and widely used in Bangladesh. However, recent study shows that a significant number of patients, 39.4% do not meet criteria for ASDAS CRP clinically important criteria and only 26% meets the criteria for ASDAS major improvement to tofacitinib 10mg daily. 102 patients of refractory ax-SpA meeting the enrollment criteria will be taken and put on 10mg tofacitinib. Those who fail to attain ASDAS CRP major improvement criteria at 12 weeks will be put on 15mg tofacitinib and both the groups will be compared at week 24 in a dose escalation study.

No studies have been done on 15mg tofacitinib for ax-SpA, such a study will provide us ground for escalation of tofacitinib. Regarding safety issues, FDA has warned against the use of 20mg tofacitinib but not for 15mg. Baseline characteristics and variables will be recorded at initiation of therapy, 4th, 12th and 24th week. The study will take place in Rheumatology outdoor, BSMMU and Modern One Stop Arthritis Care and Research Centre, Dhaka from July 2022- April 2024. Patient's socio-demographic and clinical data will be taken in a semi-structured questionnaire. At every follow up detailed history, thorough physical examination and investigations will be done to evaluate the efficacy and adverse effects. Patients will be assessed for response, ASDAS-CRP, ASDAS-ESR, ASAS-20, BASFI, BASDAI, BASMI, ASQoL, SF-36, MASES and VAS will be noted. CBC, CRP, S. creatinine and S. ALT will be done during follow up.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1000
    • Bangabandhu Sheikh Mujib Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years
2. Patient fulfill the ASAS classification criteria for ax-SpA
3. Patient fulfill the definition of refractory axial ax-SpA
4. Patients with ASDAS-CRP>2.1

Exclusion Criteria:

1. Patient currently taking or had prior treatment with bDMARD or tsDMARD (including JAK inhibitor)
2. Patient with any active or history of any chronic or recurrent or serious or opportunistic infection/sepsis (including tuberculosis)
3. Hemoglobin (Hb) < 9 g/dl
4. White blood cell count < 4000, Neutrophil count < 1000, Platelet count < 100000/mm3
5. Live vaccines within 3 months prior to the first dose
6. GFR less than 50 mL/min
7. Alanine aminotransaminase (ALT) more than 2 times of ULN
8. Pregnant or breast feeding females of child-bearing potential not using highly effective contraception
9. Evidence or history of malignancy
10. New York Heart Association Class III and IV congestive heart failure
11. Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib 10mg; All patient that fulfill the inclusion ans exclusion criteria will start at 10mg tofacitinib.	Drug: Tofacitinib; Tofacitinib (JAKi) is a targeted therapy option for patients with refractory ax-SpA.
Experimental: Tofacitinib 15 mg; At 3rd month, patients that do not fulfill the ASDAS major improvement criteria will get 15mg tofacitinib.	Drug: Tofacitinib; Tofacitinib (JAKi) is a targeted therapy option for patients with refractory ax-SpA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the ASDAS CRP major improvement criteria in refractory ax-SpA patients with dose escalation from 10mg to 15mg	To assess the ASDAS CRP major improvement criteria in refractory ax-SpA patients with dose escalation from 10mg to 15mg	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinicodemographic characteristics of Ax-SpA, ASDAS CRP outcome rates, quality of life, adverse effects	To compare the clinicodemographic characteristics of refractory ax-SpA patients with and without ASDAS CRP major improvement outcome; To determine the ASDAS CRP outcome rates with 10 mg and 15mg tofacitinib; To evaluate the change in quality of life with the outcome of ASDAS CRP; To evaluate the adverse effects of 10 mg and 15 mg tofacitinib	6 months

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Collaborators: Incepta Pharmaceuticals Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: March 8, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Axial Spondyloarthritis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: 4139

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes