Among other excellent articles, the latest issue addresses questions about one of the most commonly used drugs in the treatment of Sjogren's Syndrome: Plaquenil.
Question: What are the long-term effects of using Plaquenil? As an immuno-suppressant, does it actually increase the risk of other diseases?
Answer: Plaquenil, or hydroxychloroquine (HCQ), is an anti-malarial medication that has been proven to be useful in the treatment of patients with rheumatoid arthritis (RA), sys- temic lupus erythematosus (SLE) and other inflammatory and autoimmune diseases. In Sjögren’s syndrome, HCQ is believed to improve oral and ocular (eye) signs and symp- toms and has been shown to reduce inflammatory markers in saliva and serum, such as sedimentation rates and C-reactive protein levels. The only clinical trial in which HCQ was compared with placebo prospectively was published in 1993 and reported results on only 19 patients. It did not demonstrate any clinical ocular benefit despite improvements in hyperglobulinemia (increased immunoglobulin levels) and reductions in sedimentation rates. Despite these findings and the absence of any large prospective, placebo-controlled trials, HCQ is frequently used to treat Sjögren’s syndrome in academic and private practice settings. It is used to treat many symptoms of Sjögren’s syndrome including fatigue, joint symptoms of arthritis and arthralgias (joint pain), dry mouth and dry eyes. Similar to its use in systemic lupus erythematosus, it is felt by many clinicians that it is useful in reducing general Sjögren’s “disease activity.”
One of the reasons that physicians feel comfortable in prescribing HCQ is its low risk-to-benefit ratio. This means that the side effects of HCQ are mild and infrequent compared with its potential benefits. As with any medication, allergic reactions, including skin rashes, and non-allergic reactions can occur. The side effect that is of greatest concern is retinal toxicity. Hydroxychloroquine can deposit a pigment on the retina. This is the part of the eye that receives images that are transmitted to the brain resulting in vision. This pigment can interfere with the transmission and impair our vision. With continued treat- ment, visual loss can develop. Luckily, the pigment deposition and any visual loss are completely reversible with discontinuation of treatment with HCQ. This side effect is very unusual and in a recent study in patients with SLE and RA, documented retinal toxicity was seen in less than 1% of patients treated with HQC, and most were seen after 5-7 years of treatment. As a precaution, patients treated with HCQ are advised to get a baseline eye exam prior to starting the drug and then annually thereafter, although the authors of the above-noted study suggest that the guidelines for follow-up be revised in light of their findings and that frequent early follow-up examination may not be necessary. Nevertheless, there is no consensus on when follow-up exams should be performed and, therefore, we would recommend that you defer to the suggestions of your treating physician and ophthalmologist.
Physicians and patients consider hydroxychloroquine an immunosuppressant medication for lack of a more accurate descriptor. Perhaps an immunomodulatory medication would be a better term. The mechanism of action of HCQ has not been fully elucidated and is still a matter of debate, but it clearly has been shown to have anti-inflammatory properties mediated through modulation of the immune system. Unlike more potent immunosuppressant agents such as corticosteroids, methotrexate, azathioprine, cyclophosphamide, and rituximab, hydroxychloroquine’s effects on the immune system are subtle and not as profound.
When we consider effects of medications on the immune system, the two side effects that we are most interested in are whether, by potentially decreasing normal immuno-surveillance, they might increase the risk of infection and the development of neoplasm (cancers). There is no evidence that HCQ increases patients’ risk of getting infections or increases their risk of developing cancer.
Neil I. Stahl, MD
Want to read more from this issue? Join the Sjogren's Syndrome Foundation. It's easy to do online, if you choose. Your fees support valuable research and advocacy for Sjogren's Syndrome, and with your membership fee, you too can expect to see The Moisture Seekers appear regularly in your mailbox.