Systemic lupus erythematosus (SLE) is an autoimmune disease that affects one in a thousand individuals. Over the years, advances in treatments such as use of corticosteroids and immunosuppressants have improved life expectancy and quality of life for patients with lupus1; however, owing to its heterogenous nature in terms of organ(s) involvement and disease manifestations, SLE remains an area of high unmet need. Although pharma companies have successfully identified the immense hidden commercial opportunity for SLE and many drugs are currently in development for the disease, the clinical trial failure rates in SLE are high. Rituximab, blisibimod, epratuzumab, and tabalumab are among the many drugs whose development were discontinued owing to dissatisfactory results in failed clinical trials. To date, Benlysta is the only approved biologic for the treatment of SLE. Currently, there are only a few key therapies that have managed to enter late-stage clinical trials. Based on its positive results in Phase II studies, Stelara (ustekinumab) is one such therapy which has the potential to cross the clinical trial and regulatory hurdles needed for approval.

Stelara is an anti-IL 12/23 agent which is currently approved for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and moderate to severe Crohn’s disease. It is also progressing through development for SLE, as a Phase II study of Stelara in SLE ( NCT02349061; N=102) recently yielded positive results. The study met the primary end point as measured by the SLE Responder Index (SRI)-4 response rate at week 24, with a significantly higher proportion of patients in the Stelara group showing improvements in lupus disease activity compared with placebo (60 percent vs. 31 percent, respectively). Likewise, the patients receiving Stelara experienced significantly greater changes from baseline in SLE Disease Activity-2K (SLEDAI-2K) score compared with patients receiving placebo and exhibited a greater change from baseline in Physician Global Assessment (PGA) vs. placebo at week 24. Furthermore, Stelara led to significant improvements in musculoskeletal, mucocutaneous, and immunological manifestations when compared with placebo-treated patients2,3. These results were presented at the 2017 ACR/ARHP Annual Meeting in San Diego, USA, in November 2017 and during the recently held European Lupus Conference in March 2018. These positive results from a Phase II study of Stelara are certainly encouraging, highlighting that IL-12/23 may have a role in the pathogenesis of the disease.

Although currently there are no head to head trials of Stelara with Benlysta, an indirect comparison of Stelara’s Phase II trials results with Benlysta’s Phase III trial results−( NCT 00410384; N=819) which include the same primary end point of SRI-4 response rate−reveals that Stelara has a better overall efficacy profile than Benlysta. If Stelara depicts similar efficacy and safety in its planned Phase III trials, it could win approval for an indication which has seen only a single drug approval in over half a century.

However, we should be cautious in equating an approval with commercial success since it is too early to make conclusions on the anticipated challenges that Stelara will face, including a well-entrenched lupus therapy like Benlysta. On one hand, with ever increasing competition in the psoriasis market and the already crowded Crohn’s disease space, Janssen could strive hard to gain an indication extension for Stelara in lupus in order to sustain its blockbuster position for the coming years. Undoubtedly, Stelara’s reputation in other immune indications and time on the market would be an advantage if it gets launched for SLE. GSK, on the other hand, is leaving no stone unturned to keep Benlysta on its growth trajectory. The recently announced BLISS-BELIEVE trial ( NCT03312907) to evaluate the efficacy and safety of belimumab administered in combination with rituximab is one such initiative. Notably, Benlysta is also being evaluated for its efficacy and safety in lupus nephritis. Moreover, based on the design of its clinical trials, Stelara is presumably destined to compete with same patient population as Benlysta, so Benlysta would have a competitive edge owing to greater physician experience. Several emerging therapies such as anifrolumab, rigerimod, and atacicept which are already in Phase III trials, with good chances of gaining approval, are bound to present additional hurdles to Stelara’s success in lupus.

To summarize, although it’s too early to comment on Stelara’s future in the SLE space, with its prospective approval and subsequent launch likely years away, it would certainly be a welcome addition to the SLE armamentarium for rheumatologists treating the disease, offering them an alternative for refractory SLE patients with musculoskeletal and mucocutaneous manifestations.

DRG recently explored the unmet need in SLE through a survey of 90 U.S. and European rheumatologists. For more details on this research, please contact


  1. Bakshi J, et al. Unmet Needs in the Pathogenesis and Treatment of Systemic Lupus Erythematosus. Clin Rev Allergy Immunol. 2017; 10.1007/s12016-017-8640-5.
  2. van Vollenhoven R, et al. Efficacy and Safety of Ustekinumab, an Interleukin 12/23 Inhibitor, in Patients with Active Systemic Lupus Erythematosus: Results of a Phase 2, Randomized Placebo-Controlled Study. 2017; Abstract no. 6L ACR/ARHP annual meeting.
  3. van Vollenhoven R, et al. Efficacy and Safety of Ustekinumab, an Interleukin 12/23 Inhibitor, in Patients with Active Systemic Lupus Erythematosus: Results of a Phase 2, Randomized Placebo-Controlled Study. 2018; Lupus Science & Medicine. 5 (Suppl 1) A28-A29; DOI: 10.1136/lupus-2018-abstract.45. European Lupus Meeting.

Relevant Reports:

Systemic Lupus Erythematosus [ Access & Reimbursement | Detailed, Expanded Analysis: Systemic Lupus Erythematosus ]

Systemic Lupus Erythematosus [ Current Treatment | Detailed ]

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