EP_078. Greater risk of weight gain with JAK inhibitors compared to biologic DMARDs in rheumatoid arthritis patients: Data from the BITORA study

Siti Aisyah Abdul Ahmad¹, Shereen Ch'ng Suyin², Ee Ling Lai³, Mooi Khin H’ng⁴, Kiah Loon Ng⁵, Suhaida Ahmad Maulana⁶, Azwarina Hanim Ramlan⁷, Syang Pyng Gan⁸, Chuang Tin Quake⁴, Farah Nadiah Sulaiman⁹, Phing Sue Wong¹⁰, Chun Ruh Ng¹¹, Voon Ya Tay¹⁰, Azrianna Nurfizan Azmi¹², Jasmine Yew Sze Yin¹³, Chou Luan Tan⁷, Hui Jen Ding¹⁴, Dayang Masyrinartie Suahilai¹⁵, Sharifah Aishah Wan Mohamad Akbar¹⁶, Ying Fun Ng⁴, Surendran Ramasamy¹⁷, Ravathy A/P Nasadurai², Norliza Zainudin², Ping Seung Ong¹⁸, Avreena Kaur Bhullar A/P Authar Singh³, Choon Seong Ng⁹, Mohd Hakimi Nordin⁵, Hwai Jien Lee⁹, Seow Ching Ng⁷, Shakira Selvananda¹⁵, Mariam Hamid Mustapha⁶, E'rlene Low Li Ern⁹, Hoh Yuen Loong¹, Nurnabila Syafiqah Muhamad Rizal¹, Siti Fariha Ghazali¹, Nur Jannah Zulkefli¹, Nor Jannatul Husna Jamaludin¹, Swee Gaik Ong¹⁴, Siti Mariam Ab Rahim¹², Liza Mohd Isa⁹, Kar Hoo Lee¹⁰, Ing Soo Lau², Cheng Lay Teh¹⁶, Eashwary Mageswaren⁶, Suk Chyn Gun¹⁷,  Nur Aida Sabrina Mohd Rashid¹, Haziqah Itqan Alias¹, Nurul Aain Ahmad Fauzi¹, Nor Shuhaila Shahril⁹,  Habibah Mohd Yusoof², Hwee Cheng Chong¹³, Asmahan Mohamed Ismail⁵, Ai Lee Lim⁴, Asmah Mohd¹⁷, Mollyza Mohd Zain² and Chun Lai Too^1*

1. Immunogenetic Unit, Allergy and Immunology Research Center, Institute for Medical Research, National Institutes of Health Complex, Ministry of Health Malaysia, 40170 Shah Alam, Selangor, Malaysia

2. Department of Medicine, Hospital Selayang, Ministry of Health Malaysia, 68100 Batu Caves, Selangor, Malaysia

3. Department of Medicine, Hospital Taiping, Ministry of Health Malaysia, 34000 Taiping, Perak, Malaysia

4. Department of Medicine, Hospital Pulau Pinang, Ministry of Health Malaysia, 10450 George Town, Pulau Pinang, Malaysia

5. Department of Medicine, Hospital Raja Perempuan Zainab II, Ministry of Health Malaysia, 15200 Kota Bharu, Kelantan, Malaysia

6. Department of Medicine, Hospital Tengku Ampuan Rahimah, Ministry of Health Malaysia, 41200 Klang, Selangor, Malaysia

7. Department of Medicine, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, 05460 Alor Setar, Kedah, Malaysia

8. Department of Medicine, Hospital Serdang, Ministry of Health Malaysia, 43000 Kajang, Selangor, Malaysia

9. Department of Medicine, Hospital Putrajaya, Ministry of Health Malaysia, 62250 Putrajaya, Malaysia

10. Department of Medicine, Hospital Sultan Ismail, Ministry of Health Malaysia, 81100 Johor Bahru, Johor, Malaysia

11. Department of Medicine, Hospital Pakar Sultanah Fatimah, Ministry of Health Malaysia, 84000 Muar, Johor, Malaysia

12. Department of Medicine, Hospital Sultanah Nur Zahirah, Ministry of Health Malaysia, 20400 Kuala Terengganu, Terengganu, Malaysia

13. Department of Medicine, Hospital Melaka, Ministry of Health Malaysia, 75400 Melaka, Malaysia

14. Department of Medicine, Hospital Kuala Lumpur, Ministry of Health Malaysia, 50586 Kuala Lumpur, Malaysia

15. Department of Medicine, Hospital Tengku Ampuan Afzan, Ministry of Health Malaysia, 25100 Kuantan, Pahang, Malaysia

16. Department of Medicine, Hospital Umum Sarawak, Ministry of Health Malaysia, 93586 Kuching, Sarawak, Malaysia

17. Department of Medicine, Hospital Tuanku Ja’afar, Ministry of Health Malaysia, 70300 Seremban, Negeri Sembilan, Malaysia

18. Department of Medicine, Hospital Raja Permaisuri Bainun, Ministry of Health Malaysia, 30450 Ipoh, Perak, Malaysia

 *Corresponding author: Too Chun Lai. This email address is being protected from spambots. You need JavaScript enabled to view it.

 ABSTRACT

 INTRODUCTION: Weight gain in patients with rheumatoid arthritis (RA) may impact quality of life, treatment adherence, and outcomes. Preclinical studies suggest that biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) influence weight via effects on adipose tissue and metabolism, potentially affecting treatment response.

 OBJECTIVE(S): This study aimed to investigate the changes in body weight among RA patients treated with bDMARDs versus JAKi.

 MATERIALS & METHODS: The BITORA study is a multicentre, prospective, longitudinal study conducted across 17 Malaysian rheumatology centres. A total of 248 patients with moderate-to-severe RA who initiated bDMARDs (59.7%) or JAKi (40.3%) were enrolled between March 2022 and November 2024. Patients were followed up at 1, 3, 6, 9, and 12 months. Demographics, disease activity, comorbidities, concurrent RA-related medications, and corticosteroid use were collected. Body weight was recorded at each visit, and changes between 9 and 12 months were analysed and compared between treatment groups.

 RESULTS: Among 209 RA patients with available data, 89.5% were female, and the majority were Malay (48.3%), followed by Chinese (23.9%) and Indian (23.4%). Approximately 90% of the patients tested positive for anti-cyclic citrullinated peptides (anti-CCP) and/or rheumatoid factor (RF) autoantibodies. During the study period, the body weight of nine patients (4.3%) remained unchanged. Weight loss occurred in 30% of patients on bDMARDs and 22.5% of patients on JAKi. Conversely, weight gain was observed in 65.0% of patients on bDMARDs and 74.2% of those on JAKi. Notably, the proportion of patients with more than 10% of weight gain was approximately twice as high in the JAKi group compared to the bDMARDs group. Two-thirds of patients in both treatment groups were biologic-naïve at baseline.

 CONCLUSION: JAKi therapy may be associated with a higher risk of significant weight gain (more than 10%) compared to bDMARDs therapy. Given that the majority of patients were biologic-naïve, these weight changes are likely attributable to the effects of initial DMARD exposure rather than prior treatment history.

 KEYWORDS: Rheumatoid Arthritis, Biologics, JAK Inhibitors, Body Weight