乌鸦传媒

Baseline factors including age, race, and steroid use were predictive of flare in patients with systemic lupus erythematosus (SLE) who tapered or discontinued treatment with hydroxychloroquine, Canadian researchers found.

In a multivariable analysis, the adjusted hazard ratio for flare was 1.74 (95% CI 1.23-2.45) among patients who tapered their hydroxychloroquine and had been on prednisone at baseline, according to Sasha Bernatsky, MD, PhD, of McGill University in Montreal, and colleagues.

And among patients who discontinued the drug, the risk for flare was increased for Black patients (HR 1.61, 95% CI 1.03-2.51) and for those who were ages 25 and younger at the time of SLE diagnosis (HR 1.75, 95% CI 1.29-2.38), the researchers reported online in .

"Although our study was originally motivated by the desire to better understand personalized therapy in SLE, our findings take on new importance in the current setting, where physicians and patients may face shortages of hydroxychloroquine, due to interest in this drug as a potential therapy for COVID-19," Bernatsky and colleagues wrote.

In addition, patients discontinue or cut back on hydroxychloroquine for other reasons including the potential for retinal toxicity, which can develop in one-fifth of patients using the drug long term.

Therefore, to explore the effects of tapering or discontinuing hydroxychloroquine among patients with SLE, the researchers analyzed data from five clinical cohorts in Canada for patients enrolled during the years 1999 to 2019.

The primary endpoint was a composite outcome of events representative of SLE flare, which included an increase of at least four points on the SLE Disease Activity Index (SLEDAI), hospitalization for SLE, and/or augmented SLE therapy (restart or dosage increase in hydroxychloroquine or new start of prednisone, immunosuppressants, or biologics).

Among the 1,389 patients enrolled in the five cohorts, 96.8% had used hydroxychloroquine. Of these, 398 reduced their dose and 395 discontinued the drug. Among more than 600 patients who remained on hydroxychloroquine therapy, 395 were chosen as matched controls based on disease duration and time on the drug.

The majority of patients were women, median age at SLE diagnosis was 31, and three-quarters were white. Median score on the SLEDAI at baseline was 2, and median time on hydroxychloroquine was 2.3 years.

SLEDAI scores of 4 or higher were seen in 46.7% of those who tapered, in 31.6% of those who discontinued, and in 40.2% of those who remained on treatment.

The use of prednisone at baseline was reported in 19.8% of patients who tapered their dose, in 10.6% of those who discontinued, and in 26.1% of those who maintained their hydroxychloroquine.

The primary flare outcome was observed in 261 patients who tapered, for 35.7 (95% CI 31.6-40.3) events per 100 person-years; in 226 patients who discontinued, for 29 (95% CI 25.5-33) events per 100 person-years; and in 97 patients who remained on therapy, for 16.1 (95% CI 13.2-19.6) events per 100 person-years.

Among patients who remained on their hydroxychloroquine, risk factors for flare were First Nation ethnicity (HR 2.87, 95% CI 1.21-6.76) and the use of baseline immunosuppressants (HR 1.72, 95% CI 1.08-2.71).

Among the individual components of the flare endpoint, the most common outcome was a need for augmented SLE treatment, reported in 52.8% of those tapering, 48.9% of those discontinuing, and 17.2% of those remaining on treatment. An increase of four or more points on the SLEDAI -- active disease -- was observed in 19.4% of those tapering, 20.2% of those discontinuing, and 10.3% of those maintaining treatment. Hospitalization for SLE was seen in 0.8% after tapering, 0.6% after discontinuing, and 0.3% of those maintaining treatment.

The multivariate analysis also considered the individual components of the composite flare outcome. For therapy augmentation after tapering, baseline predictive factors were Asian ethnicity (HR 1.52, 95% CI 0.99-2.32) and active disease (HR 1.62, 95% CI 1.22-2.14), and for augmentation after discontinuation, predictive factors were Black race (HR 1.69, 95% CI 1.05-2.71) and younger age at diagnosis (HR 1.48, 95% CI 1.07-2.06).

In discussing their findings, the researchers noted that prednisone use typically is considered a marker of more severe disease, and was predictive of flare, as was a SLEDAI score of 4 (active disease) or higher. "These findings confirm clinical intuition that patients with active disease are more likely to have poor outcomes, especially need for therapy augmentation," they noted.

They also pointed out that non-white patients were at greater risk in all groups, which may reflect genetic and innate disease characteristics, but may also reflect barriers to care and social/cultural factors such as medication adherence.

"The identification of multiple demographic and clinical predictors of poor outcomes after hydroxychloroquine taper/discontinuation may be useful in personalizing decisions for SLE patients (and their physicians) around medication de-escalation or maintenance, as well as monitoring for flares when hydroxychloroquine tapering or stopping is needed, such as in the current setting of potential hydroxychloroquine shortages due to interest in this drug as a therapy for COVID-19," Bernatsky and colleagues concluded.

A limitation of the study was the lack of information on reasons for tapering or discontinuing treatment, they noted.

Comment