Marta Casillas - Academia.edu (original) (raw)
Papers by Marta Casillas
ChemInform, May 22, 2010
Alkaloids U 0600 A Stereocontrolled Entry to 3-Functionalized cis-3a-Methyloctahydroindoles: Buil... more Alkaloids U 0600 A Stereocontrolled Entry to 3-Functionalized cis-3a-Methyloctahydroindoles: Building Blocks for Daphniphyllum Alkaloid Synthesis.-Treatment of aldehyde (II) with benzylamine under conditions A) allows the preparation of the cis-configurated indole (IV). Its hydroboration affords alcohol (V) with the same relative configuration at the three stereogenic centers as daphniyunnine A (IX). In contrast, the double reductive amination of aldehyde (VII) bearing an ester group instead of methyl proceeds with trans-diastereoselectivity.-(CORDERO-VARGAS, A.; URBANEJA, X.;
British Journal of Dermatology
Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleu... more Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed phase 3, randomized, double-blinded, placebo-controlled trials evaluating lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD). At Week 16 of both studies, lebrikizumab 250 mg every 2 weeks (Q2W) showed statistically significant improvements in measures of skin clearance and patient reported outcomes. Patients treated with lebrikizumab achieved clinically meaningful improvements in the signs and symptoms of AD with fewer AD flares across multiple definitions than patients treated with placebo. In patients who met the protocol-defined criteria for response to lebrikizumab at Week 16, most patients treated with lebrikizumab Q2W and lebrikizumab every 4 weeks (Q4W) maintained an Investigator’s Global Assessment (...
Journal of Cutaneous Medicine and Surgery
Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis ... more Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis (AD). Objective To evaluate rapid changes in skin pain severity with baricitinib, and its impact on patient quality of life (QoL) in adults with moderate-to-severe AD who were inadequate responders to topical therapy. Methods Adult patients with moderate-to-severe AD who were inadequate responders to topical therapies ( N = 440, BREEZE-AD5 [NCT03435081]) were randomized to once-daily placebo, baricitinib 1 mg, or baricitinib 2 mg for 16 weeks. Change in Skin Pain Numeric Rating Scale (NRS) scores were assessed for the randomized population. Skin Pain NRS and Dermatology Life Quality Index (DLQI) scores were assessed for Skin Pain Response groups and patients with Body Surface Area (BSA) 10% to 50%. Results Skin Pain NRS improvement was significant versus placebo by day 1 baricitinib 2 mg (least squares mean [LSM] difference −4.4%, P = .048) and by day 2 for baricitinib 1 mg (−6.7%, P = ....
Journal of Cutaneous Medicine and Surgery, 2022
Background Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic ... more Background Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic dermatitis (AD). Rapid onset of action is important for AD treatments to improve quality of life and relieve suffering. Objectives This subanalysis evaluated how quickly baricitinib 1-mg and 2-mg reduced itch and associated sleep disturbance during the first 7 days after treatment initiation in a phase 3, double-blind, placebo-controlled trial. Methods Adult patients with AD were randomized 1:1:1 to placebo ( N = 147), baricitinib 1 mg ( N = 147) or baricitinib 2 mg ( N = 146). Patients kept daily diaries, completing the Itch Numeric Rating Scale (NRS) (itch severity from 0 = no itch to 10 = worst itch imaginable) and the Atopic Dermatitis Sleep Scale (ADSS) to measure sleep disturbance (number of nighttime awakenings because of itch). Mixed model repeated measures analysis was used to analyze change from day 1 to day 7 values. Results Patients receiving either dose of baricitinib had a ...
Arthritis & Rheumatism, 2017
Journal of the American Academy of Dermatology, 2020
h i g h l i g h t s Qualitative and mixed methods reveal complexities in teachers' motivations to... more h i g h l i g h t s Qualitative and mixed methods reveal complexities in teachers' motivations to teach. Teachers expressed two types of intrinsic value: teaching and a content area. Teachers who endorsed intrinsic value for a content area fostered more understanding. Teachers high in social utility value report more enjoyment, less anger and anxiety. Teachers' perceived teaching ability predicted most instruction and emotion outcomes.
Journal of Dermatological Treatment, 2021
BACKGROUND Baricitinib previously demonstrated improvements in itch and sleep disturbance versus ... more BACKGROUND Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). OBJECTIVES Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. METHODS Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. RESULTS Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (-29.3 vs. -5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (-33.3 vs. -6.1%). CONCLUSIONS Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity.
Journal of the American Academy of Dermatology, 2021
Dermatology and Therapy, 2021
Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This p... more Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This post hoc analysis reports the effect of baricitinib on itch and sleep disturbance during the first week of treatment in 3 phase 3 studies. Methods: Patients were randomized 2:1:1:1 to once-daily placebo or baricitinib 1 mg, 2 mg, or 4 mg in the BREEZE-AD1 and-AD2 studies and 1:1:1 to once-daily placebo or baricitinib 2 mg or 4 mg in the BREEZE-AD7 study. Topical corticosteroids were only allowed in BREEZE-AD7. Patients completed the itch numerical rating scale and atopic dermatitis sleep scale (ADSS) items 1-3 using an electronic daily diary. Data were analyzed by study as least squares mean percent change from baseline in daily scores for the randomized patients. Mixed model repeated measures analysis was used to analyze change from baseline values. Results: A total of 624, 615, and 329 patients were randomized in BREEZE-AD1,-AD2, and-AD7, respectively. Itch severity significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 (1 day after first dose) in BREEZE-AD1 and-AD7 and at day 1 in BREEZE-AD2. Patients' ability to fall asleep (ADSS item 1) significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 in all three studies. There were
Journal of the American Academy of Dermatology, 2021
Revue du Rhumatisme, 2016
Communications orales / Revue du Rhumatisme 83S (2016) A81-A162 A94 n = 1). Des cas de tumeurs ma... more Communications orales / Revue du Rhumatisme 83S (2016) A81-A162 A94 n = 1). Des cas de tumeurs malignes ont été rapportées (placebo, n = 3 ; BARI, n = 3 ; placebo secouru par BARI, n = 1). Un cas de tuberculose est survenu (ADA). Les anomalies de laboratoire ont été comparables à celles des autres études de phase 3 du BARI et peu ont conduit à l'arrêt du traitement. Conclusion.-Chez des patients atteints de PR et présentant une réponse inadéquate au MTX, le BARI administré une fois par jour a été associé à des améliorations cliniques significatives par comparaison au placebo et à l'ADA, avec un profil de tolérance acceptable.
Poster Presentations, 2017
of antibodies against individual citrullinated peptides (ACPA; Hansson M et al. Arthritis Res The... more of antibodies against individual citrullinated peptides (ACPA; Hansson M et al. Arthritis Res Ther 2012;14:R201). We have also developed a method for the quantification of autoantibodies in immune complexes (IC; Sohrabian et al. Ann Rheum Dis 2015;74(Suppl 1):A74). Here we have combined these techniques to determine ACPA profiles in RA IC. Objectives: To investigate if measurement of specific ACPA in synovial fluids (SF) and in IC from sera and SF can provide more prognostic information than conventional measurement of total ACPA and rheumatoid factor (RF) in serum. Methods: Seventy-seven RA patients with knee synovitis were treated with intra-articular triamcinolone hexacetonide, and followed until relapse. DAS28 and radiographic joint damage according to Larson-Dale were recorded. Anti-CCP2, IgM and IgA RF and circulating C1q-binding immune complexes (CIC) were determined in paired sera and SF. IC were purified from sera and SF by binding to C1q-coated beads, and thereafter eluted with a procedure developed in our laboratory. Antibodies against 19 citrullinated peptides were investigated with a custom-made microarray assay based on the ImmunoCAP ISAC system (Phadia AB, Sweden) in sera and SF as well as in IC from sera and SF. The target peptides were filaggrin 307-324 (CCP1), vimentin peptides 60-75 and 2-17, fibrinogen peptides α36-50" α563-583, α580-600, α621-635, β36-52, β60-74, β62-81 (with citrullination in positions 72 and 74, respectively), α-enolase 5-21 (CEP-1), peptides 1, 5, Z1, Z2 and Bla26 from hnRNP, and histone 4 peptides 14-34 and 31-50. Cutoffs were established in relation to healthy controls. Backward stepwise regression was used to investigate what factors determined Larsen Dale index, DAS28, and duration of remission after steroid treatment. Independent factors were anti-CCP2, IgM RF, IgA RF, CIC, number of ACPA peptide reactivities, and number of ACPA reactivities in IC, all measured both in serum and paired SF. Results: A considerable proportion of anti-CCP2 negative patients had multiple ACPA in SF, and in IC fractions. High DAS28 associated with reactivity against 7/19 peptides in serum and 9/19 in SF. High Larsen score associated with number of specific ACPA in SF IC and with CIC in SF. DAS28 levels associated with IgM RF in SF and with CIC in SF, and steroid response duration with number of specific ACPA in serum and in SF IC. Conclusions: We found ACPA in SF, and especially in the IC fraction of SF, in a sizeable fraction of anti-CCP2 negative patients. Number of peptide-specific ACPA (but not anti-CCP2 levels) associated with radiological destruction and length of remission after intra-articular steroid therapy. Our data do not support a role for any unique ACPA specificity in RA pathogenesis. Instead, the number of individual ACPA specificities may be important.
Current medical research and opinion, 2017
A comprehensive review was performed to investigate the effect of route of administration on medi... more A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the diffe...
Annals of the Rheumatic Diseases, 2016
Background Poor compliance with drugs for rheumatoid arthritis (RA) can lead to treatment failure... more Background Poor compliance with drugs for rheumatoid arthritis (RA) can lead to treatment failure, delayed recovery, disease progression and a need for more aggressive therapy. Understanding factors associated with poor compliance has potential to improve treatment outcomes. Objectives A comprehensive review was performed to investigate: the effect of route of administration on drug compliance in RA; compliance with oral drugs in RA compared with that in a non-pain-related disease (dyslipidaemia); the effect of poor compliance on clinical outcomes; the relationship between compliance and economic outcomes, such as healthcare resource utilisation and costs; and the impact of patient education/support programmes on compliance. Methods Comprehensive database searches and searches of the reference lists of relevant publications were performed to identify studies investigating drug compliance in adults with RA being treated with conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidaemia being treated with statins. Studies had to be published after 1998 and in English, and had to involve ≥6 months of follow up. Compliance data were extracted and compared between the different routes of drug administration in RA, and between the two diseases for oral agents. Results A total of 33 and 22 papers underwent data extraction for RA and dyslipidaemia, respectively. The definitions and range of compliance values across studies was wide, making comparisons between drug formulations and diseases difficult. Within the constraints of the analysis, compliance and persistence rates were broadly similar for the different routes of drug administration in RA (compliance for intravenous [i.v.], subcutaneous [s.c.] and oral drugs, respectively: 68%, 59–73% and 33–107% [some patients took extra doses] at 6 months; 38–64% [i.v.] and 16–97% [s.c.] at 1 year; and 58–71% [oral] at 2 years). Compliance with oral drugs was also broadly similar across the two diseases (for RA: 33–107% at 6 months, 58–71% at 2 years; for dyslipidaemia: 40–100% at 6 months, 72–75% at 2–3 years). Poor compliance had clinical consequences in both diseases: greater disease activity, pain and functional disability in RA, and increased serum cholesterol levels and risk of ischaemic heart disease in dyslipidaemia (Figure). The only factors associated with compliance/persistence across both diseases were age, race and the extent of copayment/out-of-pocket expenses. Over 1–3 years, poor compliance with biologic RA drugs led to increased resource use and medical costs but lower total direct costs due to reduced biologic (s.c. and i.v.) drug costs. By contrast, poor compliance with dyslipidaemia drugs resulted in increased total direct costs. For RA, compliance improved with patient education/support. Conclusions The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug compliance in RA. Disclosure of Interest B. Fautrel: None declared, A. Balsa: None declared, P. Van Riel: None declared, M. Casillas Employee of: Employee of Eli Lilly and Company, J.-P. Capron Employee of: Employee of Eli Lilly and Company, C. Cueille Employee of: Employee of Eli Lilly and Company, I. De La Torre Employee of: Employee of Eli Lilly and Company
European Psychiatry, 2015
BackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies sho... more BackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns.MethodsFrom 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD whocompletedatomoxetine treatment at long-term (24 weeks;n= 1443) and/or short-term (12 weeks;n= 2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling.ResultsBased on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term ...
BMC psychiatry, Jan 2, 2015
Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a c... more Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use. Cases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014). A total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) wer...
European Psychiatry, 2014
Introduction: In studies of adult patients with attention deficit hyperactivity disorder (ADHD) a... more Introduction: In studies of adult patients with attention deficit hyperactivity disorder (ADHD) atomoxetine (ATX) has demonstrated substantial improvements in ADHD symptomatology using Conners’ Adult ADHD Rating Scales (CAARS). The pattern suggests incremental response over time with no clear plateau of response. Objectives: To identify patterns of response to ATX in adult ADHD patients and to describe those trajectories over time Aims: To determine if patients have distinct response trajectories using CAARS in two populations, short term (12 weeks) and long term (24 weeks) treatment data. Methods: Data from 2502 ATX patients, who had an investigator-rated CAARS total score at ≥ short or long term time point, The numbers of trajectory clusters for short term (n=2502) and long term (n=1139) data were identified using hierarchical clustering methods. Linear mixed modelling was used to describe those different trajectories over time. Results: Using CAARS total, 4 trajectory clusters were identified in short term treated patients and 5 in long term. Three out of 4 short term trajectory clusters (representing 84% of patients) and 4 out 5 long term (representing 96%) showed more successful trajectories. In general clusters with less improvement were those with the worst baseline CAARS and minimal initial improvement. Distinct trajectory patterns of response were found that were incremental over time in all clusters. Conclusions: Adult ADHD patients receiving atomoxetine have individual trajectories of response that can be divided into 4 short term trajectories and 5 long term trajectories. Further analysis is ongoing to describe these cohorts.
ChemInform, May 22, 2010
Alkaloids U 0600 A Stereocontrolled Entry to 3-Functionalized cis-3a-Methyloctahydroindoles: Buil... more Alkaloids U 0600 A Stereocontrolled Entry to 3-Functionalized cis-3a-Methyloctahydroindoles: Building Blocks for Daphniphyllum Alkaloid Synthesis.-Treatment of aldehyde (II) with benzylamine under conditions A) allows the preparation of the cis-configurated indole (IV). Its hydroboration affords alcohol (V) with the same relative configuration at the three stereogenic centers as daphniyunnine A (IX). In contrast, the double reductive amination of aldehyde (VII) bearing an ester group instead of methyl proceeds with trans-diastereoselectivity.-(CORDERO-VARGAS, A.; URBANEJA, X.;
British Journal of Dermatology
Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleu... more Lebrikizumab is a monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed phase 3, randomized, double-blinded, placebo-controlled trials evaluating lebrikizumab for the treatment of moderate-to-severe atopic dermatitis (AD). At Week 16 of both studies, lebrikizumab 250 mg every 2 weeks (Q2W) showed statistically significant improvements in measures of skin clearance and patient reported outcomes. Patients treated with lebrikizumab achieved clinically meaningful improvements in the signs and symptoms of AD with fewer AD flares across multiple definitions than patients treated with placebo. In patients who met the protocol-defined criteria for response to lebrikizumab at Week 16, most patients treated with lebrikizumab Q2W and lebrikizumab every 4 weeks (Q4W) maintained an Investigator’s Global Assessment (...
Journal of Cutaneous Medicine and Surgery
Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis ... more Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis (AD). Objective To evaluate rapid changes in skin pain severity with baricitinib, and its impact on patient quality of life (QoL) in adults with moderate-to-severe AD who were inadequate responders to topical therapy. Methods Adult patients with moderate-to-severe AD who were inadequate responders to topical therapies ( N = 440, BREEZE-AD5 [NCT03435081]) were randomized to once-daily placebo, baricitinib 1 mg, or baricitinib 2 mg for 16 weeks. Change in Skin Pain Numeric Rating Scale (NRS) scores were assessed for the randomized population. Skin Pain NRS and Dermatology Life Quality Index (DLQI) scores were assessed for Skin Pain Response groups and patients with Body Surface Area (BSA) 10% to 50%. Results Skin Pain NRS improvement was significant versus placebo by day 1 baricitinib 2 mg (least squares mean [LSM] difference −4.4%, P = .048) and by day 2 for baricitinib 1 mg (−6.7%, P = ....
Journal of Cutaneous Medicine and Surgery, 2022
Background Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic ... more Background Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic dermatitis (AD). Rapid onset of action is important for AD treatments to improve quality of life and relieve suffering. Objectives This subanalysis evaluated how quickly baricitinib 1-mg and 2-mg reduced itch and associated sleep disturbance during the first 7 days after treatment initiation in a phase 3, double-blind, placebo-controlled trial. Methods Adult patients with AD were randomized 1:1:1 to placebo ( N = 147), baricitinib 1 mg ( N = 147) or baricitinib 2 mg ( N = 146). Patients kept daily diaries, completing the Itch Numeric Rating Scale (NRS) (itch severity from 0 = no itch to 10 = worst itch imaginable) and the Atopic Dermatitis Sleep Scale (ADSS) to measure sleep disturbance (number of nighttime awakenings because of itch). Mixed model repeated measures analysis was used to analyze change from day 1 to day 7 values. Results Patients receiving either dose of baricitinib had a ...
Arthritis & Rheumatism, 2017
Journal of the American Academy of Dermatology, 2020
h i g h l i g h t s Qualitative and mixed methods reveal complexities in teachers' motivations to... more h i g h l i g h t s Qualitative and mixed methods reveal complexities in teachers' motivations to teach. Teachers expressed two types of intrinsic value: teaching and a content area. Teachers who endorsed intrinsic value for a content area fostered more understanding. Teachers high in social utility value report more enjoyment, less anger and anxiety. Teachers' perceived teaching ability predicted most instruction and emotion outcomes.
Journal of Dermatological Treatment, 2021
BACKGROUND Baricitinib previously demonstrated improvements in itch and sleep disturbance versus ... more BACKGROUND Baricitinib previously demonstrated improvements in itch and sleep disturbance versus placebo in adults with moderate-to-severe atopic dermatitis (AD). OBJECTIVES Examine if itch and sleep improvements are associated with better quality of life (QoL) and productivity in patients with AD. METHODS Data were drawn from BREEZE-AD5 (NCT03435081). Itch and sleep improvement at Week 16 were defined using ≥4-point improvements in the Itch Numeric Rating Scale and ≥1.5 decreases in the number of nighttime awakenings since baseline, respectively. Patients with and without improvements were compared on Dermatology Life Quality Index (DLQI) and Work Productivity and Activity Impairment-AD scores. Changes from baseline were analyzed using ANCOVA with last observation carried forward. Proportions were analyzed using logistic regression with non-responder imputation. RESULTS Greater proportions of patients with versus without itch improvement indicated no impact of AD on QoL (37.7 vs. 1.8%). Patients with itch improvement had greater decreases in work time impaired (-29.3 vs. -5.6%). More patients with versus without sleep improvement reported no effect of AD on QoL (25.5 vs. 1.1%); patients with better sleep experienced larger reductions in work time spent impaired (-33.3 vs. -6.1%). CONCLUSIONS Patients with AD who experienced itch and sleep improvement had significantly better QoL and productivity.
Journal of the American Academy of Dermatology, 2021
Dermatology and Therapy, 2021
Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This p... more Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This post hoc analysis reports the effect of baricitinib on itch and sleep disturbance during the first week of treatment in 3 phase 3 studies. Methods: Patients were randomized 2:1:1:1 to once-daily placebo or baricitinib 1 mg, 2 mg, or 4 mg in the BREEZE-AD1 and-AD2 studies and 1:1:1 to once-daily placebo or baricitinib 2 mg or 4 mg in the BREEZE-AD7 study. Topical corticosteroids were only allowed in BREEZE-AD7. Patients completed the itch numerical rating scale and atopic dermatitis sleep scale (ADSS) items 1-3 using an electronic daily diary. Data were analyzed by study as least squares mean percent change from baseline in daily scores for the randomized patients. Mixed model repeated measures analysis was used to analyze change from baseline values. Results: A total of 624, 615, and 329 patients were randomized in BREEZE-AD1,-AD2, and-AD7, respectively. Itch severity significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 (1 day after first dose) in BREEZE-AD1 and-AD7 and at day 1 in BREEZE-AD2. Patients' ability to fall asleep (ADSS item 1) significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 in all three studies. There were
Journal of the American Academy of Dermatology, 2021
Revue du Rhumatisme, 2016
Communications orales / Revue du Rhumatisme 83S (2016) A81-A162 A94 n = 1). Des cas de tumeurs ma... more Communications orales / Revue du Rhumatisme 83S (2016) A81-A162 A94 n = 1). Des cas de tumeurs malignes ont été rapportées (placebo, n = 3 ; BARI, n = 3 ; placebo secouru par BARI, n = 1). Un cas de tuberculose est survenu (ADA). Les anomalies de laboratoire ont été comparables à celles des autres études de phase 3 du BARI et peu ont conduit à l'arrêt du traitement. Conclusion.-Chez des patients atteints de PR et présentant une réponse inadéquate au MTX, le BARI administré une fois par jour a été associé à des améliorations cliniques significatives par comparaison au placebo et à l'ADA, avec un profil de tolérance acceptable.
Poster Presentations, 2017
of antibodies against individual citrullinated peptides (ACPA; Hansson M et al. Arthritis Res The... more of antibodies against individual citrullinated peptides (ACPA; Hansson M et al. Arthritis Res Ther 2012;14:R201). We have also developed a method for the quantification of autoantibodies in immune complexes (IC; Sohrabian et al. Ann Rheum Dis 2015;74(Suppl 1):A74). Here we have combined these techniques to determine ACPA profiles in RA IC. Objectives: To investigate if measurement of specific ACPA in synovial fluids (SF) and in IC from sera and SF can provide more prognostic information than conventional measurement of total ACPA and rheumatoid factor (RF) in serum. Methods: Seventy-seven RA patients with knee synovitis were treated with intra-articular triamcinolone hexacetonide, and followed until relapse. DAS28 and radiographic joint damage according to Larson-Dale were recorded. Anti-CCP2, IgM and IgA RF and circulating C1q-binding immune complexes (CIC) were determined in paired sera and SF. IC were purified from sera and SF by binding to C1q-coated beads, and thereafter eluted with a procedure developed in our laboratory. Antibodies against 19 citrullinated peptides were investigated with a custom-made microarray assay based on the ImmunoCAP ISAC system (Phadia AB, Sweden) in sera and SF as well as in IC from sera and SF. The target peptides were filaggrin 307-324 (CCP1), vimentin peptides 60-75 and 2-17, fibrinogen peptides α36-50" α563-583, α580-600, α621-635, β36-52, β60-74, β62-81 (with citrullination in positions 72 and 74, respectively), α-enolase 5-21 (CEP-1), peptides 1, 5, Z1, Z2 and Bla26 from hnRNP, and histone 4 peptides 14-34 and 31-50. Cutoffs were established in relation to healthy controls. Backward stepwise regression was used to investigate what factors determined Larsen Dale index, DAS28, and duration of remission after steroid treatment. Independent factors were anti-CCP2, IgM RF, IgA RF, CIC, number of ACPA peptide reactivities, and number of ACPA reactivities in IC, all measured both in serum and paired SF. Results: A considerable proportion of anti-CCP2 negative patients had multiple ACPA in SF, and in IC fractions. High DAS28 associated with reactivity against 7/19 peptides in serum and 9/19 in SF. High Larsen score associated with number of specific ACPA in SF IC and with CIC in SF. DAS28 levels associated with IgM RF in SF and with CIC in SF, and steroid response duration with number of specific ACPA in serum and in SF IC. Conclusions: We found ACPA in SF, and especially in the IC fraction of SF, in a sizeable fraction of anti-CCP2 negative patients. Number of peptide-specific ACPA (but not anti-CCP2 levels) associated with radiological destruction and length of remission after intra-articular steroid therapy. Our data do not support a role for any unique ACPA specificity in RA pathogenesis. Instead, the number of individual ACPA specificities may be important.
Current medical research and opinion, 2017
A comprehensive review was performed to investigate the effect of route of administration on medi... more A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the diffe...
Annals of the Rheumatic Diseases, 2016
Background Poor compliance with drugs for rheumatoid arthritis (RA) can lead to treatment failure... more Background Poor compliance with drugs for rheumatoid arthritis (RA) can lead to treatment failure, delayed recovery, disease progression and a need for more aggressive therapy. Understanding factors associated with poor compliance has potential to improve treatment outcomes. Objectives A comprehensive review was performed to investigate: the effect of route of administration on drug compliance in RA; compliance with oral drugs in RA compared with that in a non-pain-related disease (dyslipidaemia); the effect of poor compliance on clinical outcomes; the relationship between compliance and economic outcomes, such as healthcare resource utilisation and costs; and the impact of patient education/support programmes on compliance. Methods Comprehensive database searches and searches of the reference lists of relevant publications were performed to identify studies investigating drug compliance in adults with RA being treated with conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidaemia being treated with statins. Studies had to be published after 1998 and in English, and had to involve ≥6 months of follow up. Compliance data were extracted and compared between the different routes of drug administration in RA, and between the two diseases for oral agents. Results A total of 33 and 22 papers underwent data extraction for RA and dyslipidaemia, respectively. The definitions and range of compliance values across studies was wide, making comparisons between drug formulations and diseases difficult. Within the constraints of the analysis, compliance and persistence rates were broadly similar for the different routes of drug administration in RA (compliance for intravenous [i.v.], subcutaneous [s.c.] and oral drugs, respectively: 68%, 59–73% and 33–107% [some patients took extra doses] at 6 months; 38–64% [i.v.] and 16–97% [s.c.] at 1 year; and 58–71% [oral] at 2 years). Compliance with oral drugs was also broadly similar across the two diseases (for RA: 33–107% at 6 months, 58–71% at 2 years; for dyslipidaemia: 40–100% at 6 months, 72–75% at 2–3 years). Poor compliance had clinical consequences in both diseases: greater disease activity, pain and functional disability in RA, and increased serum cholesterol levels and risk of ischaemic heart disease in dyslipidaemia (Figure). The only factors associated with compliance/persistence across both diseases were age, race and the extent of copayment/out-of-pocket expenses. Over 1–3 years, poor compliance with biologic RA drugs led to increased resource use and medical costs but lower total direct costs due to reduced biologic (s.c. and i.v.) drug costs. By contrast, poor compliance with dyslipidaemia drugs resulted in increased total direct costs. For RA, compliance improved with patient education/support. Conclusions The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug compliance in RA. Disclosure of Interest B. Fautrel: None declared, A. Balsa: None declared, P. Van Riel: None declared, M. Casillas Employee of: Employee of Eli Lilly and Company, J.-P. Capron Employee of: Employee of Eli Lilly and Company, C. Cueille Employee of: Employee of Eli Lilly and Company, I. De La Torre Employee of: Employee of Eli Lilly and Company
European Psychiatry, 2015
BackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies sho... more BackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns.MethodsFrom 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD whocompletedatomoxetine treatment at long-term (24 weeks;n= 1443) and/or short-term (12 weeks;n= 2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling.ResultsBased on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24 weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term ...
BMC psychiatry, Jan 2, 2015
Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a c... more Olanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use. Cases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014). A total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) wer...
European Psychiatry, 2014
Introduction: In studies of adult patients with attention deficit hyperactivity disorder (ADHD) a... more Introduction: In studies of adult patients with attention deficit hyperactivity disorder (ADHD) atomoxetine (ATX) has demonstrated substantial improvements in ADHD symptomatology using Conners’ Adult ADHD Rating Scales (CAARS). The pattern suggests incremental response over time with no clear plateau of response. Objectives: To identify patterns of response to ATX in adult ADHD patients and to describe those trajectories over time Aims: To determine if patients have distinct response trajectories using CAARS in two populations, short term (12 weeks) and long term (24 weeks) treatment data. Methods: Data from 2502 ATX patients, who had an investigator-rated CAARS total score at ≥ short or long term time point, The numbers of trajectory clusters for short term (n=2502) and long term (n=1139) data were identified using hierarchical clustering methods. Linear mixed modelling was used to describe those different trajectories over time. Results: Using CAARS total, 4 trajectory clusters were identified in short term treated patients and 5 in long term. Three out of 4 short term trajectory clusters (representing 84% of patients) and 4 out 5 long term (representing 96%) showed more successful trajectories. In general clusters with less improvement were those with the worst baseline CAARS and minimal initial improvement. Distinct trajectory patterns of response were found that were incremental over time in all clusters. Conclusions: Adult ADHD patients receiving atomoxetine have individual trajectories of response that can be divided into 4 short term trajectories and 5 long term trajectories. Further analysis is ongoing to describe these cohorts.