Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE.

OBJECTIVES: To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. METHODS: The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. RESULTS: Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [-9 (0.9) vs -6 (0.9), difference (95% CI): -3 (-6, -1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. CONCLUSION: This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02662985.

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

[Adverse events during biological therapy -- focusing on dermatological side-effects]. / Biológiai terápia során észlelt mellékhatások -- különös tekintettel a borgyógyászati szövodményekre.

UNLABELLED: Biological response modifiers, especially tumour necrosis factor inhibitors have been proved to be very effective in the treatment of various immune mediated rheumatological, gastroenterological and dermatological diseases in the last 15 years. With their increasing use, the incidence of their adverse effects are more precisely defined. The aim of this cohort study was to analyse the adverse effects occurred within the study period in patients receiving biological therapy for rheumatological and dermatological autoimmune diseases. METHODS: 324 patients within a 3 years study period were treated with biological response modifiers (adalimumab: 92, etanercept: 107, infliximab: 125). The primary diagnoses were rheumotoid arthritis (n = 174), ankylosing spondylitis (n = 60), psoriatic arthritis (n = 11), and psoriasis vulgaris (79). RESULTS: Hypersensitive reactions were observed in 11 of the patients (3.4%), 7 of which were serious and needed treatment termination. Infections constituted the majority of side effects, which were localised to skin in 10 (3.1%) and to respiratory tract in 9 (2.8%). However, most of these were mild or moderate reactions. Malignant skin tumour developed in 1 case (0.3%) only. Drug induced inflammatory disorders occurred in some cases: onset of new psoriasis was observed in 1 and flares of the existing disease were detected in additional three. Lichenoid exanthema developed in one. (n = 5, 1.5%) CONCLUSION: The use of TNF-α blockers may provoke a broad spectrum of dermatological side effects. Our results suggest that the majority of these are infectious and inflammatory disorders, the latter may relatively often appear as drug induced psoriasis. The occurrence of malignancies was very low in our series.