Baricitinib
Baricitinib is an oral Janus kinase (JAK) inhibitor that blocks JAK-1 and JAK-2. It is licensed for use in many countries for the treatment of adults with rheumatoid arthritis, and has been granted fast-track designation by the US Food and Drug Administration (FDA) in order to accelerate development and regulatory review for the treatment of systemic lupus erythematosus (SLE).[159]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
[160]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
[161]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
[162]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.[163]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
One phase 3 trial (SLE_BRAVE-1) demonstrated that a high dose of baricitinib significantly increased the rate of SLE Responder Index (SRI) - 4 response, defined as a reduction in the SLE Disease Activity Index (SLEDAI) by ≥4 points, with no worsening of the British Isles Lupus Assessment Group (BILAG) index (new grade 1A or 2B score) or deterioration from baseline ≥0.3 points in the physician global assessment, in patients with SLE compared with standard care at 52 weeks.[164]Morand EF, Vital EM, Petri M, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-I). Lancet. 2023 Mar 25;401(10381):1001-10.
http://www.ncbi.nlm.nih.gov/pubmed/36848918?tool=bestpractice.com
However, in a further phase 3 trial (SLE-BRAVE-II) of safety and efficacy of baricitinib for patients with SLE, no new adverse effects were reported at 52 weeks, but the beneficial results of the previous phase 3 trail replicated.[165]Petri M, Bruce IN, Dörner T, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 3 trial (SLE-BRAVE-II). Lancet. 2023 Mar 25;401(10381):1011-19.
http://www.ncbi.nlm.nih.gov/pubmed/36848919?tool=bestpractice.com
Obinutuzumab
Obinutuzumab is a monoclonal antibody that targets CD20, a protein found on specific B cells. 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.[166]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.[167]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
Obinutuzumab is approved by the FDA and the European Medicines Agency (EMA) for the treatment of adults with lupus nephritis.
Itolizumab
Itolizumab is an investigational 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.[168]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 an investigational 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).[169]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
CABA-201
CABA-201, an investigational fully human CD19 chimeric antigen receptor (CAR) T-cell immunotherapy, has been granted fast-track designation by the FDA. A phase 1/2 open label study to evaluate the safety and efficacy of CABA-201 for patients with active lupus nephritis or SLE without renal involvement is underway.[170]ClinicalTrials.gov. RESET-SLE: a phase 1/2 open-label study to evaluate the safety and efficacy of CABA-201 in subjects with active systemic lupus erythematosus. Oct 2025 [internet publication].
https://clinicaltrials.gov/study/NCT06121297