Factors Predictive of SLE Flare After HCQ Taper/Discontinuation Save

The benefits of hydroxychloroquine in lupus are many, but if you were to withdraw HCQ? A recent study of five Canadian cohorts, suggests that certain baseline variables, including age, race, and steroid use,  were predictive of flare in patients with systemic lupus erythematosus (SLE) who tapered or discontinued treatment with hydroxychloroquine.

Treatment with hydroxychloroquine is central to the management of SLE and has been shown to improve lipids, decrease insulin resistance and thrombosis, and prevent SLE flares. The antimalarial drug can also increase response to other treatment regimens for patients with renal involvement. Overall, its use is associated with improved survival and decreased organ damage. However, it has been unclear who would do well after tapering or discontinuing hydroxychloroquine and who would experience complications related to SLE flares.

According to a Canadian study published in Arthritis Care & Research, baseline factors including age, race, and steroid use were predictive of flare in patients with SLE who tapered or discontinued treatment with hydroxychloroquine.

The following subgroups were found to be at higher risk of experiencing flares: non-Caucasian patients (particularly Black, Asian, and First Nation people); those ages 25 and younger at SLE diagnosis; and patients with active disease, including those on prednisone or immunosuppressive agents, reported Sasha Bernatsky, MD, PhD, of McGill University in Montreal, and colleagues.

While sustained use of hydroxychloroquine might greatly reduce SLE flares, concerns remain over retinal toxicity -- an irreversible complication affecting 20% of long-term users. Almost a third of SLE patients discontinue the drug by 5 to 8 years.

Shortages of hydroxychloroquine due to its supposed potential as a COVID-19 treatment have also added to the dilemma faced by patients and physicians.

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.

Almost all of the 1,389 patients (96.8%) enrolled in the five cohorts had used hydroxychloroquine. Of these, 398 tapered the drug 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 primary endpoint was a composite outcome of events representative of SLE flare, which included an increase of at least four points on the SLEDAI, hospitalization for SLE, and/or augmented SLE therapy (restart or dosage increase in hydroxychloroquine or new start of prednisone, immunosuppressants, or biologics).

In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events.

Among patients who tapered their hydroxychloroquine and had been on prednisone at baseline, the adjusted hazard ratio for flare was 1.74 (95% CI 1.23-2.45).

The researchers noted the loss of 240 patients to follow-up, 62 consent withdrawals, and 35 deaths during follow-up; all of these patients were censored at the corresponding times.

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

For those 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 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 the individual components of the composite outcome, 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 indicating 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.

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 remained on hydroxychloroquine.

Among patients who remained on 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).

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); 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).

Study limitations included its exploratory nature, which precluded adjustment of the analyses for multiple comparisons; underestimation of hydroxychloroquine exposure; and a lack of certainty as to the reasons for tapering or discontinuing the drug.

Source Reference: Arthritis Care & Research 2020; DOI: 10.1002/acr.24548