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| CASE SERIES |
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| Year : 2023 | Volume
: 55
| Issue : 4 | Page : 263-265 |
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A case series on tofacitinib-induced weight gain
Kanisha Shah1, Dhaiwat Shukla2, Manish Patel2, Supriya Malhotra1
1 Department of Pharmacology, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
2 Department of Medicine, VS General Hospital, Ahmedabad, Gujarat, India
| Date of Submission | 22-Mar-2023 |
| Date of Decision | 13-Jul-2023 |
| Date of Acceptance | 08-Aug-2023 |
| Date of Web Publication | 11-Sep-2023 |
Correspondence Address:
Supriya Malhotra
Department of Pharmacology, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijp.ijp_158_23
Janus kinase inhibitor tofacitinib belongs to a group of targeted synthetic disease-modifying anti-rheumatic drugs, also known as small molecule inhibitors. They are oral drugs with a novel strategy to treat inflammatory diseases. The major concern with the use of these drugs is a high risk for infections and other potential side effects. Here, we have focused on reporting one of the rare side effects of tofacitinib, weight gain. We have reported six cases of tofacitinib-induced weight gain in patients of ankylosing spondylitis, rheumatoid arthritis, and vasculitis.
Keywords: Autoimmune disease, Janus kinase inhibitor, tofacitinib, weight gain
How to cite this article:
Shah K, Shukla D, Patel M, Malhotra S. A case series on tofacitinib-induced weight gain. Indian J Pharmacol 2023;55:263-5 |
| » Introduction | |  |
Tofacitinib inhibits Janus kinase (JAK) enzymes, specifically JAK1 and JAK3, which play a crucial role in the signaling pathways of various cytokines involved in autoimmune diseases such as rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), leading to a reduction in inflammation and disease activity.[1]
Tofacitinib commonly causes upper respiratory tract infections, headache, diarrhea, and hypertension. It also raises the risk of serious infections such as tuberculosis, herpes zoster and fungal infections, malignancies such as lymphoma, thrombosis, and liver damage.[2]
Tofacitinib may cause weight gain, a rare side effect reported in several studies. We reported six cases to the Indian Pharmacopoeia Commission with unique ID numbers IN-IPC-300735393, IN-IPC-300735401, IN-IPC-300735421, IN-IPC-300735665, IN-IPC-300744097, and IN-IPC-300744286. Causality assessments of these Adverse Drug Reactions are “Possible” as the risk of weight gain may vary depending on the individual patient's medical history, lifestyle factors, and other medications they are taking.
| » Case Reports | | |
Case 1
A 37-year-old male with axial-AS for 3 years presented with polyarthralgia and was prescribed NSAIDs. Tofacitinib 5 mg BD was later prescribed due to worsening of symptoms. After 5 months, lab reports and Disease Activity Score (AS-DAS) showed improvement, but the patient gained a weight of 12.8 kg during this period. The patient was planned to stop tofacitinib. Here is the comparison [Table 1] of the patient's laboratory reports before and after the treatment with tofacitinib. | Table 1: Patient's blood reports before and after taking treatment with tofacitinib
Click here to view |
Case 2
A 40-year-old female with axial-AS since 5 years had negative HLA-B27 and diabetes. Her weight was 76 kg. She was taking tablet Naprosyn 500 mg for 6 months, but due to poor disease control, she was prescribed tablet tofacitinib 5 mg BD. After a month of use, she gained 6 kg. The medication was discontinued. Her latest weight was 82 kg.
Case 3
A 42-year-old woman with known RA for 8 years was taking tablet methotrexate 15 mg once a week, tablet leflunomide 10 mg, tablet hydroxychloroquine 300 mg, and tablet ibuprofen. Despite taking multiple Disease-modifying antirheumatic drugs (DMARDs), her DAS-28 was 3.78, indicating moderate disease activity. She was shifted from tablet leflunomide to tablet tofacitinib 5 mg BD. Her DAS-28 score began to improve. After 5 months, her weight had increased from 50.6 to 58.9 kg. She was then switched to injection rituximab and tablet tofacitinib was stopped. She followed strict diet and exercises. Her weight began to decrease, dropping 3 kg over a few months to 55.6 kg.
Case 4
An elderly female patient with a 9-year history of RA was taking tablet prednisolone 2.5 mg, tablet methotrexate 10 mg, tablet hydroxychloroquine 300 mg, but her disease activity remained high. DAS-28 score was 5.78. Tofacitinib 5 mg BD was added and the disease was well controlled after 3 years. Although the patient's weight increased from 60 to 70 kg, tofacitinib continued due to its benefits outweighing the risks.
Case 5
A 27-year-old Jain male with a deficiency of adenosine deaminase-2 (DADA-2) vasculitis experienced weight gain while taking tofacitinib 5 mg as an alternative treatment when etanercept was unavailable in a general hospital. He was also taking tablet prednisolone 15 mg and tablet folic acid 5 mg. As his weight increased from 57 to 62 kg in 2 months, tofacitinib was planned to be stopped.
Case 6
A 45-year-old woman with RA for 7 years was taking methylprednisolone 4 mg and tofacitinib 5 mg BD for 1.5 years, resulting in a significant weight gain from 78 to 97 kg. However, after stopping the drugs 8 months ago, her weight decreased to 88 kg.
| » Discussion | | |
Tofacitinib is used in patients with active autoimmune diseases where the disease is not well controlled by the first-line treatments. In our case series, patients with RA and AS received Tofacitinib due to poor disease control by traditional drugs. RA patients were given tofacitinib alongside DMARDs or corticosteroids. DADA-2 vasculitis lacks standard treatment protocols, but anti-tumor necrosis factor agents are currently preferred.[3]
One of the observational studies of Novikova et al. has shown weight gain in 75% of the patients with moderate-to-high RA disease activity during treatment with tofacitinib (median increase weight gain of more than 3 kg, from 1 to 12 kg) and 26% out of them have a weight gain of 10% or more.[4] In our case series, the mean increase in patient's weight was 9.6 kg, ranging from 5 to 19 kg. Four of them showed a significant weight gain of more than 10% [Figure 1]. | Figure 1: Comparison of patient's weights (in kg) before and after the treatment with tofacitinib
Click here to view |
Tofacitinib commonly causes headache and diarrhea as nonserious side effects, while weight gain is less frequent. The mechanism behind tofacitinib-induced weight gain is not fully understood, but it's thought to be linked to a reduction in JAK3 activity, which plays a role in obesity's pathogenesis. Decreased JAK3 levels can result in chronic inflammation, poor glucose metabolism, and fatty liver disease. Blocking the JAK/Stat3/PI3K-dependent pathway can cause leptin and insulin resistance as well as adipocyte angiogenesis and obesity.[4]
In a study by Chikugo et al., JAK inhibition's impact on body composition was examined in RA patients treated with tofacitinib. Fat mass increased significantly, likely due to various factors such as cytokines, steroids, and reduced physical activity.[5] Corticosteroids may have contributed to weight gain in three patients in the case series.
Tofacitinib patients require weight and body mass index monitoring and lifestyle changes to manage weight gain.[4] One of the patients from the study lost 3 kg with these modifications. These measures should start with patient counseling. As seen in our five cases, discontinuing tofacitinib can also manage weight gain.
| » Conclusion | | |
This effect of tofacitinib is scarcely reported in India. Physicians must be aware of such effects. More and more clinical studies and postmarketing surveillance should run in such a manner that provides the safety data of tofacitinib and further guides the physicians to prescribe tofacitinib appropriately.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| » References | | |
| 1. | Hodge JA, Kawabata TT, Krishnaswami S, Clark JD, Telliez JB, Dowty ME, et al. The mechanism of action of tofacitinib – An oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Clin Exp Rheumatol 2016;34:318-28.  |
| 2. | Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: Integrated analysis of data from the global clinical trials. Ann Rheum Dis 2017;76:1253-62. |
| 3. | Human A, Pagnoux C. Diagnosis and management of ADA2 deficient polyarteritis nodosa. Int J Rheum Dis 2019;22 Suppl 1:69-77. |
| 4. | Novikova DS, Udachkina HV, Markelova EI, Kirillova IG, Misiyuk AS, Demidova NV, et al. Dynamics of body mass index and visceral adiposity index in patients with rheumatoid arthritis treated with tofacitinib. Rheumatol Int 2019;39:1181-9. |
| 5. | Chikugo M, Sebe M, Tsutsumi R, Iuchi M, KIshi J, Kuroda M, et al. Effect of Janus kinase inhibition by tofacitinib on body composition and glucose metabolism. J Med Invest 2018;65:166-70. |
[Figure 1]
[Table 1]
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