Clinical Trial Summary
Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease characterized by
dysfunction of the exocrine glands, which results in sicca symptoms in affected patients.
JAK/STAT signaling pathway is activated and playing as a key pathway in the differentiation
and activation of many lymphocytes, so that affect the pathogenesis of many autoimmune
diseases including pSS. JAK inhibitors have also been widely used in the treatment of
rheumatoid arthritis and other autoimmune diseases.
Some studies have confirmed that JAK/STAT pathway is activated in patients with pSS, and JAK
inhibitor may be effective for pSS. Filgotinib, the selective JAK1 inhibitor, is one of the
"secondary generation" JAK inhibitors developed these years. Lee et al. found that filgotinib
suppressed the IFN-induced transcription of differentially expressed genes and BAFF in human
primary salivary gland epithelial cells. In addition, filgotinib-treated mice exhibited
increased salivary flow rates and marked reductions in the lymphocytic infiltration of SGs,
indicating that JAK inhibitors may be a novel therapeutic approach for pSS. A randomized
phase 2 study is currently in progress to assess the safety and efficacy of filgotinib in
adult subjects with active Sjogren's syndrome. So far, there is no evidence of the safety and
efficacy of baricitinib in patients with pSS.
Baricitinib, an oral inhibitor of JAK1/JAK2, was the second JAK inhibitor approved for
clinical use in RA. It has been approved for the treatment for moderate to severe active RA
in adult patients who have responded inadequately to, or are intolerant to, one or more
disease-modifying anti-rheumatic drugs (DMARDs). The efficacy and safety of baricitinib in RA
have been extensively evaluated in pre-clinical animal models of arthritis, as well as in
clinical studies. There are also some reports of baricitinib used in other autoimmune
diseases, such as systemic lupus erythematosus, dermatomyositis and PMR/GCA. In a
double-blind, multicenter, randomized, placebo-controlled, 24-week phase 2 study across 11
countries, baricitinib treatment at a dose of 4 mg dose significantly improved the signs and
symptoms of active SLE, with a high-resolution rate of 67% in SLEDAI-2K arthritis or rash,
and showed a safety profile consistent with previous studies into baricitinib to treat RA.
The study focused on specific organ manifestations, which benefited patients treated with
baricitinib with rash and arthritis. So far, only one study has focused on the potential
efficacy of baricitinib in SS. In that study, Aota et al. demonstrated baricitinib suppressed
IFN-γ-induced CXCL10 expression in human salivary gland ductal cells and suggested its
potential for the treatment of SS. Based on these, we thought that baricitinib might have
therapeutic benefit in patients with pSS.
We plan to explore the efficacy and safety of baricitinib in patients with pSS in this
single-center, prospective, open label, 24-weeks pilot study. We plan to enroll 11 patients
diagnosed as active pSS in Peking Union Medical College Hospital, Beijing, China. They will
be treated with baricitinib 2mg once a day for 24 weeks. We'll evaluate the disease activity
mainly by ESSDAI and ESSPRI score. And we'll also record the adverse reactions. The primary
endpoint of the study is the change of ESSDAI score at 12 weeks. The secondary endpoints
include: the minimal clinically important improvement (MCII) of ESSDAI, which was defined as
an improvement of ESSDAI of at least three points; the change of ESSDAI score at 24 weeks;
the change of ESSPRI and PGA score at 12 and 24 weeks; and remissions of organ involvement at
12 and 24 weeks. The main inclusion criteria include: (1) ≥18 years old, (2) fulfill the
criteria of the 2016 American College of Rheumatology (ACR)/European League Against
Rheumatism (EULAR) classification for primary SS, (3) with moderate or high activity of SS,
which was defined as EULAR primary SS disease activity index (ESSDAI) ≥5, and (4) with
serological activity defined as elevated C-reactive protein, erythrocyte sedimentation rate
(ESR), and/or immunoglobulin G (IgG) level (excluding acute and chronic infection and other
factors). The main exclusion criteria include: (1) patients diagnosed with an active central
nervous system disease or dysfunction of a major organ (heart, liver, kidney); (2) pregnant
or lactating women; (3) current severe infections; and (5) undergoing glucocorticoids or
immunosuppressants treatment with stable dosage for less than 12 weeks.
Baseline information included demographics, SS duration, clinical manifestations, laboratory
parameters, current medications, and disease activity. Laboratory tests, including complete
blood counts, urinalysis, liver and renal function tests, ESR, and IgG test were performed at
each visit. Disease activity was assessed using the ESSDAI, EULAR primary SS patient reported
index (ESSPRI), and physician global assessment (PGA) scores. Patients were followed up at 3
and 6 months after the initiation of baricitinib treatment. The concomitant medications
including steroids and immunosuppressants were not changed during the study.
Response to treatment, or minimal clinically important improvement (MCII), was defined as an
improvement of ESSDAI of at least three points23. Remissions of arthritis, cutaneous
involvement, and hematological involvement were defined as no points earned in the
corresponding items of the ESSDAI scoring system. The improvement of interstitial lung
disease (ILD) was determined by evaluating the patient symptoms and radiographic changes in
the pulmonary high-resolution computed tomography (HRCT) scan.
