This is the first study to estimate the time to LLDAS and the predictors of time to LLDAS in the Asian population. Furthermore, we used a matrix model to illustrate the time to LLDAS in patients with different baseline characteristics, aiming to provide references to the future clinical trials and the clinical practice.
This study demonstrated that LLDAS is attainable as a treatment target for Chinese patients with SLE. In our SLE cohort, the time to LLDAS was 1.7 years, which was longer than that in the Johns Hopkins Lupus Cohort (1.1 years) mainly consisting of Caucasian and African-American patients . The difference may be partly due to the different disease activity at baseline. In their cohort, 50.7% of patients had PGA ≤1 and 53.8% had SLEDAI ≤4 at baseline, while the percentages in our patients were only 28.7% and 24.0%, respectively.
Our study confirmed that baseline disease activity could strongly influence the LLDAS achievement. Some previous studies found that patients with LLDAS ≥50% of follow-up time had a lower level of SLEDAI at baseline [14, 22, 23], and other studies found that baseline SLEDAI ≤4 was a predictor of achieving LLDAS and maintaining LLDAS for 5 years [15, 26]. The present study showed that patients with lower disease activity (by PGA or SLEDAI-2K) at baseline were more quickly to achieve LLDAS. Particularly, some components of SLEDAI including active nephritis, serositis and hypocomplementemia were found to be predictors of achieving LLDAS with longer time, while arthritis was found to be predictors of earlier LLDAS achievement.
Our study indicated that the age at disease onset of SLE could influence the LLDAS achievement. Previous researches had demonstrated that patients with juvenile-onset SLE had higher disease activity, received more intensive prednisone and IMs therapy, had more organ damage and a two-fold higher mortality rate, compared with adult-onset patients [38-42]. Recently, some studies reported that patients who were in LLDAS ≥50% time or observations during follow-up had older age at diagnosis of SLE [14, 22, 23]. In the present study, patients with older age at disease onset were demonstrated to have shorter time to LLDAS after adjusting other factors, including daily prednisone dose, SLEDAI and PGA.
It should be noted that early treatment was a strong positive predictor for LLDAS achievement. Babaoglu et al found that patients with disease duration ≤1 year had shorter time to LLDAS . Our study confirmed the association and further found that treatment-naïve was also a positive predictor of LLDAS achievement. Moreover, patients with organ damage before recruitment were found to require longer time to achieve LLDAS. These evidences indicated early treatment could provide more opportunities for quick achievement of LLDAS.
Our study revealed that the patients who received HCQ as an initial treatment were able to achieve LLDAS faster. HCQ has been used in SLE for over half a century. Increasing evidences have been emerging to suggest the beneficial effects of HCQ, including reducing prednisone dose, decreasing disease activity, preventing lupus flares and organ damage accrual, and improving survival rate [43-49]. Babaoglu et al found that patients who received HCQ at baseline had a shorter time to LLDAS in univariable Cox model . Our study further demonstrated that HCQ prescription was a strong independent predictor of shorter time to LLDAS, even after adjusted by disease activity factors. Apart from HCQ, other treatments were also evaluated in the present study. We found that those patients who used IMs at baseline required longer time to achieve LLDAS. A study from Tsang et al also showed that patients using IMs at baseline had a lower possibility of maintaining LLDAS ≥50% time during follow-up .
We found that complicating SS in SLE patients predicted a shorter time to LLDAS. A study by Baer et al showed that patients with both SLE and SS were a distinct subset with older age at SLE diagnosis and lower frequency of renal involvement , and our study revealed this overlap was also a factor of earlier achievement of LLDAS.
There were some limitations in this study. As an observational study, our data can hardly be used to evaluate the effect of different IMs on achieving LLDAS in SLE. Data from prospective intervention studies were needed to determine which medication could help to achieve LLDAS with less time. In addition, as all of the patients in this cohort were Chinese ethnicity, the conclusions may not be extrapolated to other ethnicities.