Validation of published definitions of disease remission against outcomes in SLE (studies with n ≥70 patients)
| Author (ref.) | N | Remission definition(s) | Remission achieved (%) | Association of remission with outcomes |
|---|---|---|---|---|
| General SLE | ||||
| Drenkard et al6 | 667 | ≥1 year of clinically inactive disease (serological activity allowed) that permitted withdrawal of all lupus drugs | 23.4% | 12.5-fold reduced risk for death (follow-up 11.6±6.0 years), after controlling for effects of renal disease and thrombocytopenia |
| Nossent et al7 | 200 | Physician judgement (not otherwise specified), assessed during the first year of disease | 27.5% | Lower annual relapse rates, lower average SLEDAI, lower cumulative SDI scores at the end of 5-year follow-up |
| Zen et al8 | 224 | ≥5 years complete remission with SLEDAI-2K=0 (HCQ allowed) or clinical remission with clinical SLEDAI-2K=0 (serological activity allowed) off-steroids or on low-dose steroids (HCQ/ISTs allowed) | 7.1% (complete remission), 14.7% (off-steroids), 15.6% (on steroids) | Damage accrual rates (end of 5-year follow-up): 18.8% (complete remission), 18.2% (off-steroids), 37.1% (on steroids) and 51.4% (no remission) |
| Medina-Quiñones et al9 | 532 | ≥3 years with BILAG C, D or E, no serological activity, off-steroids, off-immunosuppressives (HCQ/NSAIDs allowed) | 14.5% | Lower mortality rates (5.2% vs 13.4%; median follow-up 12 years) |
| Lupus nephritis | ||||
| Moroni et al10 | 70 | CRR: UPr* <0.2, normal renal function | 38.5% (at last follow-up) | CRR was associated with fewer renal flares, better outcome of renal flares |
| Mok et al11 | 183 | CRR: UPr <0.3, normal SAlb, normal renal function, assessed at the end of first year of therapy | 64% | Lack of CRR was associated (RR 9.9) with development of ESRD (mean follow-up 181 months) |
| Korbet et al12 | 86 | CRR: SCr ≤1.4 mg/dL, UPr ≤0.33, attained within 5 years of entering the study. See also refs 13, 14 | 43% | CRR was associated with reduced risk of progression to ESRD (HR 0.12), increased rates of patient survival at 5 and 10 years (follow-up 120±65 months) |
| Illei et al15 | 145 | CRR: SCr <130% of the lowest level during treatment, UPr <1, inactive urine sediment, off IST (HCQ and prednisone ≤10 mg/day allowed), for ≥6 months | 50.3% | Lack of CRR was associated with increased risk for severe nephritic flare (likelihood ratio (LR) 5.7) and progression to ESRD (LR 7.0) (median follow-up 116 to 123 months) |
| Hill et al16 | 71 | CRR: SCr ≤123 μmol/L, UPr ≤0.33 | N/D | Lack of CRR was associated with decreased 10-year survival rates from doubling of SCr |
| Mok et al17 | 189 | CRR: stabilised/improved SCr, UPr <1, improved serum C3 for ≥6 months, assessed at the end of IST | 55% | Lack of CRR was associated with increased risk (HR 4.5) for development of ESRD (mean follow-up 96.5 months) |
| Mok et al18 | 268 | Same as in17 | 59% | Lack of CRR was associated with increased risk (HR 4.5) for adverse outcome (doubling of SCr or ESRD or patient death) |
| Moroni et al19 | 93 | CRR: SCr <1.2 mg/dL, stable or 25% increase of baseline CrCl, UPr <0.2, inactive urine sediment | 82% (63.4% at last follow-up) | Lack of CRR was associated (RR 4.3) with development of chronic renal insufficiency (median follow-up 181 months) |
| Mak et al20 | 149 | CRR: stabilised/improved SCr, improved serum complement, UPr <1, inactive urine sediment for ≥6 months, assessed at the end of first year of therapy | 60.4% | Lack of CRR was associated with renal damage (mean follow-up 80 months) |
| Lee et al21 | 77 | CRR: SCr <1.2 mg/dL, UPr <0.2, inactive urinary sediment, for ≥6 months | 52% | Lack of CRR was associated with development of chronic renal insufficiency and/or death (follow-up 8.3±4.4 years) |
| Sun et al22 | 100 | CRR: UPr ≤0.4, normal urinary sediment, normal SAlb, normal SCr | 58% | Lack of CRR was associated with ESRD (median follow-up 60 months) |
| Ayodele et al23 | 105 | CRR: stable (±25%) renal function, UPr <0.2, assessed at the end of first year of therapy | 44.8% | CRR was associated with higher mean survival time |
| So et al24 | 117 | CRR: SCr ≤1.4 mg/dL, UPr ≤0.5, inactive urine sediment, assessed after 6 months of therapy | 50.4% | CRR was associated with reduced risk for subsequent renal flares and chronic renal failure (mean follow-up 66–76 months) |
| Reich et al25 | 98 | CRR: SCr ≤120 mmol/L (1.4 mg/dL), UPr <0.3 | 74.5% | Lack of CRR was associated with faster GFR decline (follow-up 12.4±8.4 years) |
| Alsuwaida et al26 | 77 | CRR: SCr ≤125 μmol/L, UPr ≤0.33 | 41.6% | CRR was associated with higher renal survival rate at 10 years. Lower risk for doubling of SCr |
| Dhir et al27 | 188 | UPr reduction by ≥50% to <2, inactive urine sediment, normal SCr (≤1.5 mg/dL), assessed at the end of first year | 54.6%† | Lack of remission was associated (HR 13.8) with chronic renal failure or death (median follow-up 6 years) |
| Moroni et al28 | 103 | CRR: SCr <1.2 mg/dL, stable or 25% increase of baseline CrCl, UPr <0.2, inactive urine sediment | 70.9% | CRR was associated with good renal outcome (no chronic renal insufficiency) (follow-up 156±105 months) |
| Mahmoud et al29 | 135 | CRR: SCr ≤1.2 mg/dL, and 25% increase of baseline CrCl if abnormal, or stable value if abnormal at baseline, UPr <0.2, inactive urine sediment | 59.3% | Lack of CRR in the first year was associated with adverse outcome (death, ESRD or doubling of SCr) |
| Fernandes das Neves et al30 | 105 | CRR: UPr <0.2, negative anti-double stranded DNA antibodies, normal C3 and normal SCr, for ≥5 consecutive years | 38.1% | CRR was associated with preservation of normal renal function (80% vs 43%) and reduced mortality (0% vs 22%) compared with partial/no remission group (follow-up 13.7±14.1 years) |
| Koo et al31 | 193 | CRR: UPr <0.3, for ≥6 months | 42.5% | CRR was associated with reduced risk of mortality and ESRD (follow-up 158±70 months) |
| Dall'Era et al32 | 76 | Different sets of response criteria based on a range of cut-offs of UPr, SCr and RBCs at 3, 6 and 12 months. Best criterion was UPr <0.8 at 12 months | 59.2% | Sensitivity 81% and specificity 78% for favourable long-term (7 years) renal outcome (SCr ≤1.0 mg/dL). The LUNAR study remission criterion (UPr ≤0.5, SCr±15% of baseline, inactive urine sediment) had 32% sensitivity, 91% specificity |
| Tamirou et al33 | 104 | Different sets of CR criteria based on levels of UPr, Scr and urinary RBCs at 3, 6 and 12 months. Best criterion was UPr ≤0.5 at 12 months | 49.0% | Positive predictive value 92% for achieving good long-term renal outcome (SCr ≤120% of baseline value) after median 110 months |
| Tamirou et al34 | 80 | Subgroup analysis of.33 Different sets of response criteria based on a range of cut-offs of UPr, SCr and RBCs at 3, 6 and 12 months. Best criterion was UPr <0.7 at 12 months | 63.8% | Sensitivity 71% and specificity 75% for favourable long-term (7 years) renal outcome (SCr ≤1.0 mg/dL) |
*UPr assessed by 24-hour urine collection and/or urine protein-to-creatinine ratio.
†n=71 out of 130 with available records.
BILAG, British isles lupus assessment group; CrCl, creatinine clearance; CRR, complete renal remission (or response); ESRD, end-stage renal disease; GFR, glomerular filtration rate; HCQ, hydroxychloroquine; IST, immunosuppressive treatment; LR, likelihood ratio; N/D, not described; NSAID, non-steroidal anti-inflammatory drug; RBCs, red blood cells; SAlb, serum albumin; SCr, serum creatinine; SLEDAI, Systemic lupus erythematosus disease activity index; SDI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index systemic lupus international collaborating clinics (SLICC) group damage index; UPr, proteinuria.