Update on Clinical Trials in Systemic Lupus Erythematosus

^aBAFF, B-cell activating factor; BILAG, British Isles Lupus Activity Group; BLyS, B lymphocyte stimulator; D, drug; IV, intravenous; LN, lupus nephritis; PBO, placebo; SC, subcutaneous; SLE, systemic lupus erythematosus; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.
^bSRI4, 4-point improvement in SLEDAI-2K; no clinically significant worsening (≥0.3) in PGA; and no new BILAG-2004 'A' (severe) or >1 new 'B' (moderate) organ system scores.
^cSRI5, ≥5 point improvement (reduction) in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group (BILAG) 2004 index score of A or no more than one new BILAG B score, and no worsening (increase ≥0.3 points from baseline) in physician's global assessment (PGA).
^dBICLA, British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment.

^aBILAG, British Isles Lupus Activity Group; BLyS, B lymphocyte stimulator; D, drug; IV, intravenous; LN, lupus nephritis; PBO, placebo; SC, subcutaneous; SLE, systemic lupus erythematosus; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.
^bSRI response, SLEDAI-2K score of ≥4 points, no increase in the PGA score of >0.3 point on a visual analogue scale of 0–3, no new A score on the BILAG-2004 and ≤1 new B score were considered to be SRI responders.
^cComplete remission, 24-h urinary protein excretion of 0.4 g or less, the absence of active urine sediments, serum albumin level of 35 g/l or greater, and normal serum creatinine levels.
^dPatients were randomized to get oral tacrolimus + mycophenolate mofetil versus IV cyclophosphamide ^πPatients were randomized to get oral tacrolimus versus oral mycophenolate mofetil.
^eComplete response, 1) Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate (eGFR) ≥90% of screening level if normal at screening visit, or eGFR ≥90% of 6-month, preflare value if abnormal at screening, 2) urinary protein-to-creatinine ratio<0.26 g/g (30 mg/mmol), and 3) inactive urinary sediment (RBCs and WBCs per high-power field within normal limits of central laboratory assessments; no RBC or WBC casts); reconfirmed at 4 week follow-up.
^fComplete response: (i) Urine protein-to-creatinine ratio <0.5 based on a 24-h urine collection; (ii) serum creatinine ≤1.2 mg/dl or ≤125% of baseline; and (iii) adherence to the prednisone taper to 10 mg/day by week 12.

^aBILAG, British Isles Lupus Activity Group; D, drug; IM, intramuscular; IV, intravenous; LN, lupus nephritis; OCS, oral corticosteroids; PBO, placebo; SAEs, serious adverse events; SC, subcutaneous; SLE, systemic lupus erythematosus.
^bSRI4, 4-point improvement in SLEDAI-2K; no clinically significant worsening (≥0.3) in PGA; and no new BILAG-2004 'A' (severe) or >1 new 'B' (moderate) organ system scores.
^cSustained reduction of OCS defined as: <10 mg/day and ≤day 1 dose maintained between days 85 and 169.

Authors and Disclosures

Sonali Narain and Richard Furie

Division of Rheumatology Northwell Health, Hofstra Northwell School of Medicine and The Program in Novel Therapeutics, Great Neck, New York, USA

Correspondence to
Dr Richard Furie, MD, Chief, The SLE and Autoimmune Disease Treatment Center, Division of Rheumatology Northwell Health, Professor of Medicine Hofstra Northwell School of Medicine, Director, the SLE and Autoimmune Disease Treatment Center, Director, the Program in Novel Therapeutics, 865 Northern Boulevard Suite 302, Great Neck, NY 11021, USA. Tel: +1 516 708 2550; fax: +1 516 708 2597; e-mail: rfurie@northwell.edu

Conflicts of interest
There are no conflicts of interest.

Sidebar

Key Points

• There is unprecedented drug development activity in both renal and nonrenal SLE at this time.

• Management options in patients with refractory or severe disease continue to be areas of unmet needs.

• Recent trials have highlighted the need for minimizing background heterogeneity, careful selection of study end points and disease monitoring indices as well as trial design to standardize outcomes.

• Encouraging data from recent clinical trials have renewed hope for new drugs to be approved in SLE in the near future.