IFN-α kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care. METHODS: Patients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering. RESULTS: IFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable. CONCLUSIONS: IFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering. TRIAL REGISTRATION NUMBER: NCT02665364.

Therapeutic adherence in patients with systemic lupus erythematosus: a cross-sectional study.

INTRODUCTION: The aim of the research was the study of the adherence to treatment in patients with systemic lupus erythematosus. METHODS: Cross-sectional study including 132 consecutive patients with systemic lupus erythematosus (SLICC, 2012 classification criteria). We collected clinical and socio-demographic data, socio-economic status; we assessed SLEDAI-2k disease activity, and estimated the adherence to treatment by Morisky questionnaire. RESULTS: Our results demonstrated that low adherence to treatment in patients with systemic lupus erythematosus was in only 11.36% of patients, while 43.18% and 45.46% of the patients were scored as moderate and high adherence, respectively. A moderate/high adherence to treatment was associated to a high level of education (r = -0.51, p < 0.05, 95% CI = -0.25 to -0.66), low disease activity (r = 0.38, p < 0.05, 95% CI = 0.25 to 0.53) and low indices of physician global assessment (r = -0.31, p<0.05, 95% CI = -0.23 to -0.71). The sub-analysis of the adherence to each drug demonstrated that the highest adherence was to treatment with glucocorticosteroids - 92.85%, followed by hydroxychloroquine and aspirin - 92.15% and 89.79%, respectively. CONCLUSION: In our cohort, the adherence to treatment was high in 45.46%, moderate in 43.18% and low in only 11.36% cases. High adherence to treatment was associated to low disease activity. The adherence was positively influenced by the age at the onset of the disease and a high educational level.

Chronic Miliarial Gout Associated with Carpal Tunnel Syndrome: A Very Rare Clinical Presentation.

This case report describes an unusual form of gout, called miliarial gout, in association with carpal tunnel syndrome in a 54-year-old woman. Miliarial gout was first described in 2007 and is a very rare presentation of chronic tophaceous gout. The latter condition can cause carpal tunnel syndrome, but this association has not previously been described in association with miliarial gout. In addition, the authors discuss the use of the parsimony principle in internal medicine whereby a single cause is first sought for different symptoms presenting at the same time. LEARNING POINTS: Miliarial gout, a form of chronic tophaceous gout, is a very rare clinical presentation of the disease.Patients with miliarial gout, despite subcutaneous nodules, may present with other organ involvement.Carpal tunnel syndrome in patients with gout may be caused by monosodium urate crystal deposition.

Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK-1 Inhibitor, After Short-Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials.

OBJECTIVE: JAK inhibitors have shown efficacy in rheumatoid arthritis (RA). We undertook this study to test our hypothesis that selective inhibition of JAK-1 would combine good efficacy with a better safety profile compared with less selective JAK inhibitors. METHODS: In two 4-week exploratory, double-blind, placebo-controlled phase IIa trials, 127 RA patients with an insufficient response to methotrexate (MTX) received filgotinib (GLPG0634, GS-6034) oral capsules (100 mg twice daily or 30, 75, 150, 200, or 300 mg once daily) or placebo, added onto a stable regimen of MTX, to evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of filgotinib. The primary efficacy end point was the number and percentage of patients in each treatment group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 4. RESULTS: Treatment with filgotinib at 75-300 mg met the primary end point and showed early onset of efficacy. ACR20 response rates progressively increased to week 4, and the Disease Activity Score in 28 joints using the C-reactive protein (CRP) level decreased. Marked and sustained improvements were observed in serum CRP level and other PD markers. The PK of filgotinib and its major metabolite was dose proportional over the 30-300 mg range. Early side effects seen with other less selective JAK inhibitors were not observed (e.g., there was no worsening of anemia [JAK-2 inhibition related], no effects on liver transaminases, and no increase in low-density lipoprotein or total cholesterol). A limited decrease in neutrophils without neutropenia was consistent with immunomodulatory effects through JAK-1 inhibition. There were no infections. Overall, filgotinib was well tolerated. Events related to study drug were mild or moderate and transient during therapy, and the most common such event was nausea. CONCLUSION: Selective inhibition of JAK-1 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies.