IMPORTANCE Familial chilblain lupus is a monogenic autosomal dominant form of cutaneous lupus erythematosus that in most cases is caused by mutations in the 3 prime repair exonuclease 1 (TREX1). Familial chilblain lupus presents in early childhood with cold-induced painful erythematous infiltrates leading to mutilation and is associated with systemic involvement illustrated by an elevated type I interferon (IFN) signature in the skin and blood. Effective treatment is currently not available. OBJECTIVES To evaluate the clinical response to the Janus kinase inhibitor baricitinib in familial chilblain lupus and assess the effect of cold on patient fibroblasts. DESIGN, SETTING, AND PARTICIPANTS In this case series, 3 patients with familial chilblain lupus due to TREX1 mutation underwent treatment with baricitinib for 3 months. INTERVENTIONS Doses of baricitinib, 4 mg, were administered daily for 3 months. MAIN OUTCOMES AND MEASURES Reduction of cutaneous lupus lesions was measured by the revised cutaneous lupus area and severity index, pain due to skin and joint involvement was assessed by visual analog scale, type I IFN signature in blood was determined by polymerase chain reaction, and the in vitro response of fibroblasts to cold exposure was analyzed. RESULTS All 3 patients (2 women and 1 man; mean [SD] age, 51 [24] years) showed a significant improvement of cutaneous lupus lesions with suppression of systemic type I IFN activation. One patient had a complete remission regarding pain and, in 2 patients, pain associated with joint inflammation was partially reduced. No severe adverse reactions were reported. Exposure of patient fibroblasts to cold induced a stress response and enhanced senescence along with induction of IFN-stimulated gene in vitro. CONCLUSIONS AND RELEVANCE These findings demonstrate the therapeutic efficacy of Janus kinase inhibition in a monogenic form of lupus among 3 patients and provide mechanistic insight into the process of disease exacerbation by cold in TREX1-deficient cells. This finding may be relevant to other type I IFN-mediated disorders and implicates Janus kinase inhibition as a potential therapeutic option also for multifactorial cutaneous lupus erythematosus.

Objectives To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. Methods Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). Results A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defi ned as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defi ned as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was infl uenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only infl uenced by CRF (QFT: OR 2.6; CI 1.15 to 5. 98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease. Conclusion LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specifi city.

This observational study assessed functional ability in patients treated with modified-release prednisone under conditions of normal clinical practice. Patients treated with modified-release prednisone were observed over 9 months. The primary outcome measure was the change from baseline total score using the Questionnaire on Activity Status (QAS); total QAS score ranges from 0 (severely impaired) to 100 (completely unimpaired). Other measures included Visual Analogue Scale (VAS) from 0 to 10 (where 10 = full daily performance) and Health Assessment Questionnaire Disability Index (HAQ-DI). There were no restrictions on dose of modified-release prednisone or use of concomitant therapy. A total of 1,733 patients were included in the study, with valid observations at baseline and study end for 1,185 patients (thereof 74 % female, median age 59 years, median disease duration 5 years). Mean total QAS score improved significantly after 9 months of treatment with modified-release prednisone from 54.3 to 70.2 (p < 0.001). There were also significant (p < 0.001) improvements in all three QAS dimensions (occupational performance: 66.6-78.9; household duties: 55.6-70.9; leisure activities: 51.6-69.4), daily performance (mean VAS 5.1-7.0; p < 0.001) and mean HAQ-DI score (1.35-1.00; p < 0.001). Dose of modified-release prednisone was significantly reduced (from 5.0 to 4.4 mg/day, p < 0.001) and fewer patients required biological rheumatoid arthritis (RA) treatments, analgesia and gastroprotectants. Functional ability in patients with RA improved significantly from baseline after 9 months of treatment with modified-release prednisone. This observational study, conducted under daily-practice conditions, confirms the beneficial effects of modified-release prednisone shown previously in randomised controlled trials.

BackgroundMIRAI (NCT01332994) investigated the early response to the IL-6 inhibitor tocilizumab (TCZ) within a homogeneous population of biological naïve patients (pts) with moderate/severe active RA who inadequately responded to traditional DMARDs; non-responders to TCZ subsequently received 1 cycle of rituximab (RTX; anti-CD20 therapy).ObjectivesTo assess the effects of TCZ and, if applicable, subsequent RTX treatment on PRO (SF-36, HAQ-DI, FACIT-F, VAS pain, disease activity; DA).MethodsMIRAI was a German, multicenter, two-arm, open-label, phase-IIIb-study. All pts received 4 TCZ infusions (8 mg/kg, q4w; 1st treatment period) until week 16. Partial responders (ΔDAS28>1.2 or DAS28≥2.6 and ≤3.2) received further 4 TCZ infusions; non-responders (ΔDAS28≤1.2 and DAS28>3.2) received subsequent RTX (1g each at week 16 and 18). All pts with a 2nd treatment period (TCZ or RTX) completed study at week 32. Besides the objective response measures based on the DAS28 and ACR core data set, efficacy assessments included PROs such as HAQ-DI, SF-36, FACIT-F (fatigue), patient's assessment of pain and DA (on a visual analogue scale; VAS).ResultsA total of 519 pts received TCZ in the 1st treatment period (ITT-main). At week 16, 213 partial responders to TCZ entered a 2nd TCZ period (ITT-TCZ2), only 27 non-responder initiated subsequent RTX (ITT-RTX). At week 16, clinically meaningful mean improvements in HAQ-DI, SF-36, FACIT fatigue, pain and DA were noted in the ITT-main and in partial TCZ responders; further improvement in PRO was indicated under continued TCZ treatment, although mean changes from week 16 to week 32 were minor. Slight mean improvements in HAQ-DI, SF-36, FACIT fatigue and relevant mean improvements in VAS pain and DA, particularly after administration of RTX, were reported by TCZ non-responders; 9/27 non-responders achieved ΔHAQ-DI >0.22 at week 32 compared to week 16.ConclusionsConsistent with the data of clinical efficacy, the results of the PRO also indicated rapid onset of efficacy of initial TCZ treatment with most pronounced PRO improvements until week 16 and further benefit during continued TCZ in partial responders. In TCZ non-responders mean changes in PRO were less pronounced, although 1/3 of the TCZ non-responders achieved HAQ-DI response during subsequent RTX therapy.Disclosure of InterestC. Iking-Konert: None declared, G.-R. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, BMS, Novartis, Medimmune, MSD, Pfizer, UCB, Roche, Speakers bureau: AbbVie, BMS, Novartis, MSD, Pfizer, UCB, Roche, T. Dörner: None declared, H. Schulze-Koops Consultant for: Roche, A. Rubbert-Roth: None declared, A. Engel: None declared, G. Gauler: None declared, R. Schwenke: None declared, M. Peters: None declared, H.-P. Tony Consultant for: AbbVie, Celgene, Chugai, Janssen, Lilly, MSD, Roche, Speakers bureau: AbbVie, Chugai, Roche