How to treat SLE in 2026 and beyond!

Janet Pope, MD, MPH, FRCPC

Jun 05, 2026 10:30 am

There are so many SLE trials that it will be difficult to choose how to treat your patients with lupus. I think it will come down to:

Access and familiarity
Choosing a couple of treatments that you become familiar with.

Over the last year, many new ideas have been suggested:

1 Earlier intervention (before oral immune suppressants)
Anifroliumab is doing a study in early SLE without failure of MMF/MTX/AZA
Belimumab has data showing better disease control if using Rx before failure of conventional DMARDs

2 New MOAs showing promise
CD40Li
+Phase 3 data for Dapirolizumab pegol for BICLA and SRI4 responses at 24 mg/kg IV q4w vs placebo and at EULAR 2026 steroid sparing effects while maintaining SLE improvement was demonstrated

TLR7/8i
Enpatoran is an oral TLR7/8 inhibitor
+Phase 2 RCT studying cutaneous SLE with various doses of enpatoran showing efficacy vs placebo on the CLASI

Plasmacytoid dendridic cell inhibitor
Litifilimab binds to a receptor on plasmacytoid dendritic cells blocking pDC-derived proinflammatory cytokines and chemokines – improved cutaneous lupus

3 Studies of JAKi / TYK2i to read out soon
We await the results of 2 large phase 3 RCTs
Upadacitinib a JAKi
Deucravacitinib a TYK2i – the phase 2 data LTE were presented with a durable response following patients for 3 years

4 B cell modulation / depletion
Teltacicept has a positive Ph3 trial in China and stopped the multinational RCT in SLE
Obintuzumab has +Phase 3 data for SLE and also LN
Ianalumab is being studied in SLE

5 What about deep B cell depletion?
T cell engagers are in early studies in SLE – not much data yet
CAR-T – it appears that in patients who have not responded to SoC and who are on chronic steroids, CAR-T can yield drug free remission. It should be noted that the successful patients are often young and without damage. The benefits, risks, and costs all need to be taken into consideration. The target is often CD20 and usually there is a regiment of leukapheresis (except in ‘off the shelf’ and endogenous CARs) and priming chemo is given. Antibodies seem to be reduced.

So, what to use in 2026 and beyond for SLE?

It depends on many things (relative benefit, access, safety, patient and physician preference) but there is great hope for our SLE patients now and in the foreseeable future!

References
EULAR abstracts 2026:
1. POS0310 ALLEGORY Phase III Trial in Systemic Lupus Erythematosus: Pharmacodynamic Effects of Obinutuzumab
2. POS0438 Litifilimab Improves Cutaneous Lupus Erythematosus Disease Activity: 24-Week CLASI-A Change from Baseline in AMETHYST Part A
3. POS0683 THE IMPACT OF OBINUTUZUMAB ON REMISSION AND LOW DISEASE ACTIVITY IN ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: ADDITIONAL RESULTS OF THE PHASE III ALLEGORY TRIAL
4. POS0695 LONG-TERM DISEASE CONTROL IN SLE USING LLDAS AND DORIS CRITERIA: INTEGRATED POST HOC ANALYSES FROM THE PAISLEY SLE AND LTE TRIALS
5. POS0730 GLUCOCORTICOID-SPARING MAINTENANCE OF DISEASE CONTROL IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: 48-WEEK RESULTS FROM A PHASE 3 TRIAL OF DAPIROLIZUMAB PEGOL

And other recent presentations: