The efficacy and tolerability of rIFN-alpha has been evaluated in 17 selected patients with symptomatic polycythaemia vera, diagnosed according to the PRV Study Group criteria. Complete disease control (CR) was achieved, after 1-12 months, in nine patients, with partial control in a further five cases. Three patients failed to respond. Pruritus significantly improved in 83% (10/12) of cases, following 1-28 weeks of treatment. Six patients (35%), however, were unable to tolerate rIFN-alpha, on account of weight loss, myalgia and mental changes. Overall, alpha-interferon therapy significantly improved venesection requirements, MCV and PCV values, platelet counts, pruritus scores and the degree of splenomegaly. Analysis of pooled published data (100 evaluable patients, including the present study) revealed an overall CR of 60%, a PR of 27%, and a failure rate of 13%. Significant pruritus control (> 50% improvement) occurred in 77% of cases. rIFN-alpha appears to be an effective therapy for PV-associated myeloproliferation and/or pruritus, although side-effects remain a concern. Long-term studies are now indicated to determine if the natural history of the disease is altered, in particular whether the incidence of myelofibrosis and/or leukaemic transformation is reduced.

Background:Recent EULAR ‘Points to Consider’ provide guidance on management and treatment of Women of Childbearing Age (WoCBA) with chronic rheumatic diseases (CRD: RA, axSpA, PsA). However, it is still unclear if these patients (pts) feel adequately supported to make informed treatment decisions around pregnancy and breastfeeding.Objectives:To gain insight into perspectives of women with CRD regarding disease management and pregnancy, and assess whether current clinical practice provides adequate support.Methods:WoCBA (aged 18–45 years) from Germany, France, UK, Italy, Spain (EU5), the US and Japan participated in a 20-min online survey (Jul–Oct 2017; InSites Consulting). We report data from pts with moderate-severe CRD who were pregnant or had been pregnant in the past 2–5 years.Results:622/1052 participants had CRD (RA, n=298; axSpA, n=182; PsA, n=142) and resided in the EU5 (n=306), US (n=293) and Japan (n=23). 87% pts reported having moderate CRD; 49% WoCBA stated that they had actively planned their most recent pregnancy. Fewer than half (46%) of WoCBA visited a healthcare professional (HCP) before pregnancy, of whom 53% consulted a rheumatologist among other HCPs (figure 1A). Although guidelines recommend addressing family planning/pregnancy in women with CRD before conception, 69% pts who visited an HCP before pregnancy had to initiate these discussions with their HCPs. 54% WoCBA admitted delaying their decision to become a mother; their main fear was passing on health issues to their child (figure 1B). 32% pts reported having inadequately controlled disease activity during pregnancy; 51% experienced disease improvement, 22% disease worsening. 82% pts visited an obstetrician/gynaecologist (OB/GYN) across trimesters, 68% a rheumatologist among other HCPs (figure 1A); 65% had a treatment plan aligned between different HCPs. Stopping treatment during pregnancy was largely driven by fear of harming the foetus (78%). Among the 113 pts on anti-TNFs, 22% decided to stop treatment themselves at the start of/during pregnancy, and 47% were advised to stop by their HCP. Although 89% pts reported discussing breastfeeding with an HCP (OB/GYNs were most influential), 66% mothers felt they had to decide between treatment and breastfeeding. While information provided by their HCP was generally satisfactory, pts still felt they lacked information on the impact of treatment decisions on pregnancy (38%) and breastfeeding (24%).Conclusions:Despite current treatment recommendations, WoCBA with CRD continue to have many fears and misconceptions about their journey to motherhood, due to lack of guidance and consistent information regarding family planning, pregnancy and breastfeeding. Survey findings suggest that women’s decisions to delay pregnancy and interrupt their treatment may be linked to a need for greater awareness of disease management options to optimise pregnancy outcomes. Access to this information, consultation with specialists and OB/GYNs earlier in the pregnancy planning process, and an aligned treatment plan cou...

Background and objectivesBaricitinib is an oral, reversible inhibitor of Janus kinase (JAK)1/JAK2 being developed as treatment for patients with RA. Previous studies have shown transient increases in total lymphocyte count within hours of dosing and return to baseline prior to the next dose. We examined changes over time in lymphocyte subsets in RA patients treated with baricitinib or placebo in the phase 3 RA-BUILD and RA-BEACON studies.Materials and methodsPatients had active RA with insufficient response (IR) to conventional synthetic DMARDs (csDMARDs) (RA-BUILD; N=684) or TNF inhibitors (TNFi) (RA-BEACON; N=527). Patients were randomised 1:1:1 to placebo or 2 or 4mg baricitinib QD for 24 weeks. Lymphocyte subsets and natural killer (NK) cells were quantified by flow cytometry at baseline and Week (wk) 4, wk12, and wk24. Total lymphocyte count was measured at each visit.ResultsSignificant improvements in disease activity were seen for baricitinib versus placebo in both studies. Total lymphocyte increases at wk4 for baricitinib were generally within normal ranges. Change in total lymphocyte count was similar at wk12 and wk24 for baricitinib versus placebo. In RA-BUILD/RA-BEACON, increased T-cells/µL (158.3/22.6 and 124.1/170.7 for 2mg and 4mg,p ≤ 0.05), B-cells/µL (66.7/36.8 and 82.9/74.3 for 2mg and 4mg,p ≤ 0.001), and NK-cells/µL (59.5/36.8 and 46.2/77.0 for 2mg and 4mg,p ≤ 0.01) versus placebo were seen at wk4. Decreased T-cells/µL (wk12= -20.9/0.7 and -87.6/-33.1 for 2mg and 4mg; wk24 = -117.2/-128.1 and -83.4/-53.8 for 2mg and 4mg,p ≤ 0.05) and NK-cells/µL (wk12 = -36.7/-22.0 and -57.0/-22.7 for 2mg and 4mg,p ≤ 0.001 in RA-BEACON; wk24 = -41.2/-45.0 and -53.4/-40.9 for 2mg and 4mg, p ≤ 0.05 in RA-BEACON) and increased B-cells/µL (wk12 = 65.0/49.3 and 75.1/70.2 for 2mg and 4mg, p ≤ 0.001; wk24= 24.3/22.6 and 55.2/65.0 for 2mg and 4mg,p ≤ 0.001 for 4mg) were seen later for baricitinib groups.Changes in other T- and B-cell populations were variable, but generally reflected these patterns. Decreased NK-cell count did not appear to be associated with an increased incidence of infection.ConclusionsBaricitinib produced significant clinical improvements in disease activity in csDMARD-IR and TNFi-IR RA patients. Improvements were accompanied by a variety of changes in lymphocyte counts, predominantly within normal ranges. Similar lymphocyte subset assessments will be available in a long-term extension study.

IntroductionBaricitinib (BARI), an oral selective Janus kinase (JAK) 1/2 inhibitor, approved in the EU for moderate to severe active RA.ObjectivesTo compare in vitro cellular pharmacology of BARI to upadacitinib (ABT), filgotinib (FILGO), and tofacitinib (TOFA), three JAK inhibitors (JAKis) currently approved or in clinical development.MethodsPeripheral blood mononuclear cells from healthy donors (n=6–12) were incubated with different JAKis. After cytokine stimulation, phosphorylated signal transducer and activator of transcription (pSTAT) levels were measured and IC50 calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of in vitro analysis was assessed using calculated mean concentration-time (CT) profiles over 24 hour JAKi-treated subjects (BARI 4 mg QD; ABT 15 and 30 mg QD; FILGO 100 and 200 mg QD; TOFA 5 and 10 mg BID). Time above IC50 (T>IC; h/day) and average daily% inhibition of pSTAT formation (%SI) were calculated for each JAKi, cytokine, and cell type.ResultsTested cytokines did not signal in all cell types. When signalling was detected, IC50,%SI, and T>IC for a particular JAKi exhibited similar dose dependent inhibition across cell types. For JAK1/3 dependent signalling across 4 cytokines (IL-2, 4, 15, 21), IC50 for ABT and TOFA were more potent than BARI; FILGO was the least potent. Overlaid on CT profiles, this indicated generally higher%SI and longer T>IC for ABT and TOFA compared to BARI and FILGO. For IL-6 (JAK1/2),%SI and T>IC was TOFA>BARI/ABT>FILGO and for IL-10 (JAK1/TYK2),%SI was TOFA>BARI/ABT>FILGO. IFN-γ (JAK1/2) was modulated only by BARI, ABT, and TOFA. IFN-α (JAK1/TYK2) signalling was most potently inhibited by BARI and ABT. FILGO did not appear to modulate GM-CSF signalling (JAK2/2), while%SI and T>IC were similar between BARI and ABT.ConclusionsJAKis modulate distinct cytokine pathways to differing degrees and durations over 24 hour. BARI and FILGO inhibited JAK1/3 signalling less than ABT and TOFA. No JAKis agent potently or continuously inhibited an individual cytokine signalling pathway throughout dosing interval, implying the varying efficacy and safety profiles of JAKis across disease states.AcknowledgementsStudy supportEli Lilly and Company and Incyte Corporation. Encore of ACR/ARHP-2017 Annual Scientific Meeting, Nov 4–8, 2016; San Diego, CA, USA.Disclosure of interestNone declared