Report: 2 Patients With RA Experienced Peripheral Neuropathy on JAK Inhibitor

The reports suggest patients with rheumatoid arthritis (RA) could experience secondary neurological adverse events, though the side effect appears to be rare.

A new report suggests patients who are treated with tofacitinib (Xeljanz) for rheumatoid arthritis (RA) may be at risk of neurological adverse events, such as peripheral neuropathy.

The report, published in JCR: Journal of Clinical Rheumatology, is based on just 2 cases, but the authors wrote that the events shed light on the potential for such adverse events among patients taking tofacitinib, as well as Janus kinase (JAK) inhibitors generally.

Corresponding author Gabriel J. Tobón, MD, PhD, of Icesi University, in Colombia, and colleagues, explained that infectious complications, malignancies, and cardiovascular events among patients taking JAK inhibitors have been well studied. However, the authors said there have been no reports of secondary neurological complications among this patient population until now.

The first patient in the report, a 37-year-old woman, had a history of 6 years of active seropositive RA. Due to her active disease and severe radiographic damage to her hips, hands, and knees, she was prescribed tofacitinib.

“After 2 weeks of use, although pain and stiffness improved, she started complaining of limb dysesthesias and decrease in muscle strength causing legs motor deficit but preserved osteotendinous reflexes,” Tobón and colleagues said.

Non-superior/inferior motor neuron compromise was also present, and mixed polyneuropathy was confirmed by electromyography and nerve conduction studies, the authors said. The patient’s cerebrospinal fluid was normal, and other potential causes were ruled out.

The patient eventually progressed to bed confinement. Her tofacitinib was discontinued; she was instead prescribed tocilizumab (Actemra) to treat her joint condition. She was able to walk again within a month.

In the second case, a 59-year-old patient with a history of benign renal tumor back in 2012 and unilateral nephrectomy was confirmed to have RA. Her mild renal dysfunction contra-indicated methotrexate, and so she was given chloroquine. When she failed to respond to that, she was given tofacitinib. Within a month, she was experiencing muscle weakness and decreased sensitivity in her lower limbs, Tobón and colleagues said.

After additional tests, she was given intravenous immunoglobulin (IVIG), which led to clinical improvement. She was thus continued on tofacitinib with close monitoring, for almost 2 years, the authors said.

In both cases, tofacitinib proved useful for RA control, the investigators said. However, the impacts on the first patient’s health-related quality of life prompted her to discontinue the treatment.

The authors said they were not able to identify particular risk factors for the complication they observed. They noted that a previous publication reported a case of a patient with distal symmetric polyneuropathy in a phase 3 clinical trial of a patient with psoriasis; however, that patient had higher dose of the drug than the patients in the current report.

“Drug-induced peripheral neuropathies are mostly described with antineoplastic drugs through different mechanisms such as inducing mitochondrial toxicity, oxidative stress, microtubular and ion channel dysfunction, or neuronal apoptosis, among others, using IVIG as a therapeutic alternative,” Tobón and colleagues said. “However, none of these mechanisms have been attributed directly to tofacitinib.”

Absent clear risk factors or a clear causal link, the authors said physicians treating patients with RA should be aware of the possibility of neurological adverse events in patients treated with JAK inhibitors for whom other neurological causes have been ruled out.

Reference
Navarro EP, Posso-Osorio I, Aguirre-Valencia D, Naranjo-Escobar J, Tobón GJ. Tofacitinib and Risk of Peripheral Neuropathy? Experience of 2 Cases in Patients With Rheumatoid Arthritis. J Clin Rheumatol. 2021;27(2):e58-e60. doi:10.1097/RHU.0000000000000864