“SLE has lacked validated treatment targets around which to base treat-to-target approaches that have been so successful in diseases like RA; we haven't had a treatment goal in SLE, until now,” says Eric Morand, from Monash University, Australia. Morand and colleagues from the Asia Pacific Lupus Collaboration (APLC) have now defined a lupus low disease activity state (LLDAS), because, as Morand adds, “remission is incredibly rare, so we thought that low disease activity was more realistic as a target.”

Credit: NPG

After first defining LLDAS as “a state which, if sustained, is associated with improved outcomes”, six experts from the APLC “used a nominal consensus methodology and two rounds of Delphi to reduce an original 56 items submitted for consideration to use in the definition to a core set of five domains with very high agreement,” explains Morand. LLDAS is achieved if a patient has an SLE disease activity index (SLEDAI)–2K ≤4, no new SLE disease activity compared with the previous visit, a safety of estrogens in lupus erythematosus national assessment (SELENA)–SLEDAI physician global assessment scale 0–3 of ≤1, low steroid requirement (≤7.5 mg daily) and well-tolerated standard maintenance doses of immunosuppressive drugs.

The authors then tested this definition in a single-centre SLE cohort for which prospectively acquired longitudinal data on disease activity and damage accrual were available (n = 191, monitored for an average of 3.9 years). Patients who were in LLDAS >50% of the time had reduced organ damage accrual (defined as an increase in SDI of ≥1) compared with patients who spent <50% of the time in LLDAS (relative risk 0.47, 95% CI 0.28–0.79, P = 0.005) and a reduced risk of flare (P <0.0001).

“Preliminary validation suggests that patients who achieve LLDAS more of the time have protection from adverse outcomes—the goal of therapy!” concludes Morand. The authors appreciate that this relatively small single-centre study has limitations; complete validation awaits the findings of prospective studies, which the APLC have underway.

David Isenberg (University College London, UK), who was not involved in this study, agrees that “having a 'working definition' of LLDAS provides a useful tool and is much in line with the current vogue of treating patients to target. It will enable physicians around the world to review their attempts to control lupus—and compare their approach to therapy with other groups.” Isenberg concludes that the LLDAS “represents, albeit with some caveats, a useful advance in clinical assessment of disease control.”