Anifrolumab
Anifrolumab, a monoclonal antibody type I interferon receptor antagonist, is approved by the US Food and Drug Administration (FDA) for the treatment of adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy. The European Medicines Agency has approved anifrolumab as an add-on therapy for adults with moderate to severe, active autoantibody-positive SLE despite standard treatment. In randomised placebo-controlled phase 3 trials, anifrolumab reduced oral corticosteroid dose and severity of skin disease, and improved disease response at 52 weeks, in patients with moderate to severe SLE.[138]ClinicalTrials.gov. Efficacy and safety of two doses of anifrolumab compared to placebo in adult subjects with active systemic lupus erythematosus. December 2019 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02446912
[139]Morand EF, Furie R, Tanaka Y, et al. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med. 2020 Jan 16;382(3):211-21.
https://www.nejm.org/doi/10.1056/NEJMoa1912196
http://www.ncbi.nlm.nih.gov/pubmed/31851795?tool=bestpractice.com
Long-term anifrolumab treatment suggests an acceptable safety profile with sustained improvement in SLE disease activity, health-related quality of life, and serological measures.[140]Chatham WW, Furie R, Saxena A, et al. Long-term safety and efficacy of anifrolumab in adults with systemic lupus erythematosus: results of a phase II open-label extension study. Arthritis Rheumatol. 2021 May;73(5):816-25.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252065
http://www.ncbi.nlm.nih.gov/pubmed/33225631?tool=bestpractice.com
Voclosporin
Voclosporin, a novel oral calcineurin inhibitor, is approved by the FDA for the treatment of adults with active lupus nephritis in combination with an immunosuppressive therapy regimen. In a phase 3 randomised controlled trial (RCT) of patients with lupus nephritis, voclosporin in combination with mycophenolate and low-dose corticosteroid led to a clinically significant superior complete renal response at week 52 compared with mycophenolate and low-dose corticosteroid alone (73 [41%] of 179 patients vs. 40 [23%] of 178 patients, respectively).[141]Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2021 May 29;397(10289):2070-80.
http://www.ncbi.nlm.nih.gov/pubmed/33971155?tool=bestpractice.com
Baricitinib
Baricitinib is an oral selective inhibitor of Janus kinase (JAK) that blocks JAK-1 and JAK-2. It is licensed for use in many countries for the treatment of adults with rheumatoid arthritis.[142]Lee YH, Bae SC. Comparative efficacy and safety of baricitinib 2 mg and 4 mg in patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials. Z Rheumatol. 2018 May;77(4):335-42.
http://www.ncbi.nlm.nih.gov/pubmed/28097393?tool=bestpractice.com
[143]Emery P, Blanco R, Maldonado Cocco J, et al. Patient-reported outcomes from a phase III study of baricitinib in patients with conventional synthetic DMARD-refractory rheumatoid arthritis. RMD Open. 2017 Mar 21;3(1):e000410.
https://rmdopen.bmj.com/content/3/1/e000410
http://www.ncbi.nlm.nih.gov/pubmed/28405473?tool=bestpractice.com
[144]Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52.
https://www.nejm.org/doi/10.1056/NEJMoa1507247?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dwww.ncbi.nlm.nih.gov
http://www.ncbi.nlm.nih.gov/pubmed/27028914?tool=bestpractice.com
[145]Dougados M, van der Heijde D, Chen YC, et al. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study. Ann Rheum Dis. 2017 Jan;76(1):88-95.
https://ard.bmj.com/content/76/1/88.long
http://www.ncbi.nlm.nih.gov/pubmed/27689735?tool=bestpractice.com
One 24-week placebo-controlled phase 2 RCT of baricitinib reported significant improvements in signs and symptoms of SLE among patients assigned to a high dose of baricitinib.[146]Wallace DJ, Furie RA, Tanaka Y, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018 Jul 21;392(10143):222-31.
http://www.ncbi.nlm.nih.gov/pubmed/30043749?tool=bestpractice.com
Phase 3 trials are ongoing.[147]ClinicalTrials.gov. A study of baricitinib in participants with systemic lupus erythematosus (BRAVE II). November 2021 [internet publication].
https://www.clinicaltrials.gov/ct2/show/NCT03616964
[148]ClinicalTrials.gov. A study of baricitinib in participants with systemic lupus erythematosus (SLE) (SLE-BRAVE-X). November 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03843125
Baricitinib has been granted fast-track designation by the FDA for the treatment of SLE.
Obinutuzumab
Obinutuzumab is a monoclonal antibody that targets CD20, a protein found on specific B cells. It has been granted breakthrough-therapy designation for adults with lupus nephritis by the FDA. Data from the phase 2 NOBILITY study in adult patients with proliferative lupus nephritis (n=127) indicate that obinutuzumab, in combination with standard of care (mycophenolate and a corticosteroid), is associated with enhanced complete renal response rates at 12 months compared with standard care alone.[149]ClinicalTrials.gov. A study to evaluate the safety and efficacy of obinutuzumab compared with placebo in participants with lupus nephritis (LN). November 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02550652
Results at 2 years suggest that the benefit is maintained.[150]Furie R, Aroca G, Alvarez A, et al. Two-year results from a randomized, controlled study of obinutuzumab for proliferative lupus nephritis. Abstract number 0988: ACR Convergence 2020. Arthritis Rheumatol. 2020; 72 (suppl 10).
https://acrabstracts.org/abstract/two-year-results-from-a-randomized-controlled-study-of-obinutuzumab-for-proliferative-lupus-nephritis
Itolizumab
Itolizumab is a humanised immunoglobulin G1 monoclonal antibody. It selectively targets CD6, the novel immune checkpoint receptor that plays a central role in modulating the activity and trafficking of T cells that drive several immuno-inflammatory diseases. Itolizumab has been granted fast-track designation by the FDA for the treatment of lupus nephritis. A phase 1b dose escalation study to evaluate the safety and tolerability of itolizumab in patients with SLE with or without proliferative nephritis is ongoing.[151]ClinicalTrials.gov. Study of EQ001 (itolizumab) in systemic lupus erythematosus with or without active proliferative nephritis (EQUALISE). November 2021 [internet publication].
https://www.clinicaltrials.gov/ct2/show/NCT04128579
Blisibimod
Blisibimod is a potent and selective inhibitor of B-cell activating factor (BAFF). BAFF is a mediator of differentiation, maturation, and survival of B cells. Blisibimod did not meet the primary end point (improvement in the SLE responder index at week 52) in a phase 3 RCT of 442 patients with high SLE disease activity (n=442).[152]Merrill JT, Shanahan WR, Scheinberg M, et al. Phase III trial results with blisibimod, a selective inhibitor of B-cell activating factor, in subjects with systemic lupus erythematosus (SLE): results from a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2018 Jun;77(6):883-9.
https://escholarship.org/uc/item/42p3g4xx
http://www.ncbi.nlm.nih.gov/pubmed/29563108?tool=bestpractice.com