Hydroxychloroquine for Primary Sjögren Syndrome Does Not Lower Risk of SLE

A new study is casting doubt on hopes that hydroxychloroquine use among people with primary Sjögren syndrome (pSS) might lower the risk of patients eventually developing systemic lupus erythematosus (SLE).

The new study, published in the International Journal of Rheumatic Diseases, found no association between hydroxychloroquine use and the risk of later SLE diagnosis.

Corresponding author Kuo-Tung Tang, MD, MPH, PhD, of Taichung Veterans General Hospital, in Taiwan, and colleagues, noted that recent developments in the treatment of SLE have suggested that early intervention can reduce disease burden. In particular, some believe that hydroxychloroquine might help prevent SLE if administered in the early phase of the disease’s development, Tang said, noting that the drug is effective at reducing mild relapses and limiting disease-related damage in people with SLE.

Previous research has shown that pSS may be associated with an increased risk of SLE. In those studies, 1% of people with pSS went on to be diagnosed with SLE. Many people with pSS are treated with hydroxychloroquine, so Tang and colleagues wondered whether the use of that therapy might have an impact on the risk that those patients would develop SLE.

“Despite the fact that HCQ is commonly used in pSS patients, the evidence related to the benefit of HCQ in reducing future development of SLE in pSS patients is limited,” they wrote.

Tang and colleagues used Taiwan’s National Health INsurance Research Database to identify 11,772 patients who were diagnosed with pSS between January 1, 2000, and December 31, 2010. Of those, just under 1% of patients (111 patients; 0.9%) went on to develop SLE, a figure that was in line with the previous scientific literature. In most cases, SLE developed within 5 years of the pSS diagnosis, Tang and colleagues said.

Yet, the investigators found no evidence that hydroxychloroquine use affected the risk of developing SLE. Among a subset of 78 people with SLE and 780 matched controls, all but 3 of the patients who were diagnosed with SLE had a history of hydroxychloroquine exposure. The authors said they also found no correlation between a higher dose of hydroxychloroquine and the risk of SLE.

The investigators said their findings should not be interpreted as completely refuting the possibility that hydroxychloroquine might be a useful tool in preventing or slowing the development of SLE, though they said a universal policy of using hydroxychloroquine as prophylaxis against SLE in patients with pSS might not lead to meaningful results. “Nonetheless, it is crucial to identify a subgroup of pSS patients at high risk for development of SLE before implementing preventive measures,” they wrote. “Whether it is too late to halt the progression to SLE while specific autoantibodies or clinical manifestations have already emerged is an issue requiring more investigations.”

Tang and colleagues said their research was subject to a number of limitations. They said it is possible their data set lacked sufficient power to detect an advantage for hydroxychloroquine. It is also possible their data set undercounted SLE cases, they said. In addition, they noted that their data may be confounded by a greater likelihood of receiving hydroxychloroquine among people with more severe cases of pSS.

Tang and colleagues concluded that while their data do not support the use of hydroxychloroquine as prophylaxis against SLE, they also do not believe the concept should be abandoned by investigators.

“[I]nterventional studies are needed to further explore the possible preventive role of HCQ in patients more vulnerable to the development of SLE,” they wrote.

Reference

Hsu BC, Chen YH, Lin CH, Tang KT. The association between hydroxychloroquine use and future development of systemic lupus erythematosus in patients with primary Sjögren's syndrome. Int J Rheum Dis. Published online September 11, 2022. doi:10.1111/1756-185X.14437