New Findings on Hydroxychloroquine, Denosumab

Dr. Park

In their unadjusted analysis, QTc length was significantly decreased in patients taking hydroxychloroquine compared to those not taking it. The researchers used an adjusted analysis to help account for such important confounders as age, race, steroid use, hypertension, diabetes, smoking status and aspirin use. Here, the mean adjusted QTc was comparable between the patients taking hydroxychloroquine and those not taking it. (Note: Age, current prednisone use and smoking status did predict QTc length.)

When analyzed as a categorical variable, hydroxychloroquine was also not a predictor of prolonged QTc, defined as either ≥440 ms or ≥500 ms.

The team also used stratified analysis to examine the potential interactions between hydroxychloroquine and medications known to prolong QTc, such as some antidepressants. Taken as a whole, an increase in QTc was not found in those using hydroxychloroquine in addition to one of those other medications. However, an increased QTc length was found specifically in the SLE cohort for patients taking antipsychotic medications in addition to hydroxychloroquine, compared with those taking only hydroxychloroquine.

Overall, Dr. Park says these results are in line with the results of smaller cohort studies that have not reported an association between QTc length and hydroxychloroquine use.^3-6 She noted that it is important to put in context any studies on hydroxychloroquine in COVID-19. “We must also consider the effects of COVID-19 itself on the cardiac conduction system, as well as confounding by indication, [because] sicker patients were more likely to receive hydroxychloroquine,” she said.

Dr. Park and colleagues did not have data to stratify by hydroxychloroquine dose or by length of time taking the drug, which might be a factor in potential QTc prolongation. It will also be important to get a sense of whether these data apply to patients who do have underlying cardiovascular disease (unlike study participants), because they may be the most vulnerable if QTc prolongation is ultimately found to be a risk.

Denosumab vs. Alendronate for Osteoporosis
Although glucocorticoids are a critical treatment in managing many autoimmune inflammatory diseases, they are also the leading cause of secondary osteoporosis. First-line osteoporosis treatment is oral bisphosphonate therapy, but these drugs have poor adherence rates, partly due to side effects such as esophageal irritation.¹⁰ The human monoclonal antibody denosumab (targeting RANKL ligand) is another, albeit much more expensive, option.

Several head-to-head, randomized controlled trials in postmenopausal women have suggested denosumab is more effective than oral bisphosphonates at raising bone mineral density with 12 months of treatment. However, relatively little data has been available to compare the efficacy of these approaches in long-term users of glucocorticoids. Chi Chiu Mok, MD, chief of the Division of Rheumatology of Tuen Mun Hospital, Hong Kong, discussed the contributions of his team to this topic during the third plenary session on Sunday, Nov. 8.

We must also consider the effects of COVID-19 itself on the cardiac conduction system. —Dr. Park

In a previous randomized controlled trial of 42 women taking long-term corticosteroids and bisphosphonate therapy, Dr. Mok and colleagues demonstrated that the spinal bone mineral density was significantly higher in a treatment arm that switched to denosumab.¹¹ Another key, recent study, sponsored by Amgen, of 795 patients either continuing or starting glucocorticoids found that denosumab was superior to risedronate in improving bone mineral density of the lumbar spine at 12 months.¹²