• systemic lupus erythematosus
• arthritis
• treatment
• rash
• janus kinase

Janus kinases (JAKs) are intracellular tyrosine kinases which play a key role in the signal pathways of many cytokines, such as type l interferons (IFNs), interleukin-6 (IL-6), IL-12 and IL-23.1 All these cytokines participate in the pathogenesis of systemic lupus erythematosus (SLE). Hence, inhibition of JAK signals has provided an attractive therapeutic option in SLE. Tofacitinib can inhibit JAK1/JAK3 and has been proved effective in rheumatoid arthritis (RA),2 psoriatic arthritis and ulcerative colitis. Evidence in murine lupus have shown that tofacitinib can decrease the levels of anti-double-stranded (ds) DNA and proteinuria, remit nephritis and skin rash.3 A case report proved that tofacitinib could decrease anti-dsDNA levels in inactive SLE complicated by RA.4 A phase II randomised controlled trial reported modest efficacy of a JAK1/2 inhibitor, baricitinib, in ameliorating lupus arthritis.5

To better understand the efficacy of tofacitinib in SLE, we describe, to our knowledge for the first time, the efficacy of tofacitinib 5 mg two times per day in 10 patients with SLE (nine women and one man). They were followed up for the shortest of 4 weeks and the longest for 12 months by the same medical team. At each visit, the level of anti-dsDNA (≥30 IU/mL), complement 3 (C3) level, the SLE Disease Activity Index-2000 (SLEDAI-2K), physician’s global assessment (PGA) and adverse events (AEs) were measured and assessed. Three levels of remission were defined using the SLEDAI-2K according to the guiding principles of the Definition of Remission in SLE6: complete remission: no disease activity in corticosteroid-free and immunosuppressant-free patients, antimalarials allowed; clinical remission (CR) off corticosteroids: serologically active clinical quiescent (SACQ) disease in corticosteroid-free patients; CR on corticosteroids: SACQ disease in patients taking prednisone up to 5 mg daily.

The demographic data and clinical features of the 10 patients are described in table 1. Seven patients achieved CR (two off corticosteroids and five on corticosteroids). One patient was relieved with a decreased SLEDAI-2K and PGA score but not CR, one did not improve, and one experienced a flare during the follow-up (figure 1A). Four patients quickly achieved resolution of arthritis and six patients of rash (SLEDAI-2K), respectively. However, the effectiveness of tofacitinib in rash was uncertain in two patients and completely lack of efficacy in another patient. The onset of response and reduction of corticosteroids were elaborated in online supplementary table S1. Both SLEDAI-2K (p=0.011) and PGA (p=0.042) were improved significantly at the third month (figure 1B,C). No significant serological improvement was observed in level of C3 (p=0.319) and anti-dsDNA (p=0.259) at the third month (figure 1D,E). AEs occurred in two patients. One had herpes varicella zoster, and the other had alopecia. Both of them continued the therapy, but the dosage was tapered and achieved CR finally.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

(A) Frequency of disease state and remission in patients with SLE since the treatment of tofacitinib. (B–C) The variation trends of SLEDAI-2K (p=0.011 at the third month) and PGA (p=0.042 at the third month) during the follow-up since the treatment of tofacitinib. (D–E) Levels of complement 3 and anti-dsDNA antibody during the follow-up since the treatment of tofacitinib. Statistical analyses were performed using SPSS V.23.0. (SPSS Inc, Chicago, IL, USA). The p value was two-tailed and defined as significant if <0.05. dsDNA, double-stranded DNA; PGA, physician’s global assessment; SLE, systemic lupus erythematosus; SLEDAI-2K, SLE Disease Activity Index-2000.

Tofacitinib has been found to have a rapid onset of action in 2–4 weeks in patients with RA, and this efficacy persisted for a long period,2 indicating that tofacitinib can inhibit inflammation quickly just like glucocorticoids, but avoiding the steroid-related side effects. No significant serological improvements were observed, the same as baricitinib,5 which has been demonstrated in animal models.3 The different effect on anti-dsDNA level may come from the diverse activity of SLE.

In conclusion, tofacitinib can rapidly improve the symptoms and signs of arthritis and partially improve skin rash in patients with SLE, sparing steroid to reach CR. But there is no significant change in serological parameters. Our study has limitations as an open study with a limited sample size, and in terms of the observation period inequality. Further studies are needed to confirm its efficacy and define its specific indication in patients with SLE.