Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and l... more Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (−12.3 units) or TOC (−11.7 uni...
Introduction: Hidradenitis suppurativa (HS) is a chronic, debilitating, and inflammatory skin dis... more Introduction: Hidradenitis suppurativa (HS) is a chronic, debilitating, and inflammatory skin disease. The epidemiology of HS varies greatly, with an estimated prevalence ranging from 0.03% to 4% worldwide. Similar to psoriasis (PsO), HS also exhibits a systemic inflammatory nature with a spectrum of systemic comorbidities. A large health insurance claims (HICs) database is analyzed to determine the demography and epidemiology of HS, PsO, and HS with concurrent PsO (HS-PsO) patients. Furthermore, the comorbidity profiles, including the comorbidity risk of these patient populations, are analyzed. Methods: This is a noninterventional retrospective analysis of anonymized HICs data using a subset of the Institute of Applied Health Research Berlin (InGef) database. The primary outcome is the prevalence and incidence of HS, PsO, and HS-PsO. Secondary outcomes include comorbidity profiles and a comorbidity risk analysis. Results: The prevalence and incidence of HS were 0.0681% and 0.0101%, respectively. The prevalence of HS-PsO was 0.004% (6% of the total HS population). HS patients frequently suffered from arterial hypertension (45%), nicotine dependence (46%), obesity (41%), and depression (36%), which were more common in HS-PsO patients compared with HS alone. HS patients had an increased prevalence of metabolic, psychiatric, immune-mediated, and cardiovascular diseases, e.g., overweight/obesity [odds ratio (OR): 2.65, 95% confidence interval (CI) 2.37-2.96], depression (OR: 1.55, 95% CI 1.42-1.76), or seronegative rheumatoid arthritis (OR: 2.82, 95% CI 1.61-4.94) compared with Digital Features To view digital features for this article go to
Background. Limited information exists about the very early forms of psoriatic arthritis. In part... more Background. Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reported outcomes (PROs) in very early as compared to established PsA have not been investigated to date.Methods. Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID) and global disease (VAS) in two small prospective observational studies on secukinumab 300mg over 6 months in very early disease patients (IVEPSA study; N=20) and established PsA (PSARTROS study; N=20). Cluster analysis was performed at baseline and 24-weeks follow-up.Results. While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-b...
Background. Limited information exists about the very early forms of psoriatic arthritis. In part... more Background. Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reportedoutcomes (PROs) in very early as compared to established PsA have not been investigated to date.Methods. Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID) and global disease (VAS) in two small prospective observational studies on secukinumab 300mg over 6 months in very early disease patients (IVEPSA study; N=20) and established PsA (PSARTROS study; N=20). Cluster analysis was performed at baseline and 24-weeks follow-up.Results. While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-be...
Objective. To assess if microstructural bone lesions in RA at-risk individuals are related to the... more Objective. To assess if microstructural bone lesions in RA at-risk individuals are related to the spectrum of anti-modified protein antibodies (AMPA) and affect the risk to develop RA. Methods. Cortical micro-channels (CoMiCs) as well as cortical and trabecular bone volumes were analyzed by high-resolution computed tomography in the hand joints of RA at-risk individuals. Anti-modified protein antibody (AMPA) response was profiled including reactivities against citrullinated proteins (vimentin, enolase, fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed for the development of RA. Results. RA at-risk subjects (all N=74) with broad spectrum AMPA (6-8 reactivties) had significantly more severe microstructural changes (CoMiCs: 95±35/joint; total bone volume: 265±45 HA/cm3; trabecular bone volume: 176±42; cortical bone volume: 585±138) compared to subjects with moderate (3-5 reactivties; 79±30; 293±33; 195±32, 627±91, respectively) or narrow (1-2 reactivties; 47±20, 311±34, 211±30, 674±56, respectively) AMPA reactivity. Progressors to RA had significantly higher numbers of CoMiCs and lower bone volumes (CoMiCs: 103±30 vs. 71±35; total bone volume: 258±37 vs.295±34). Furthermore, progression to RA was high in subjects with broad (48%) vs. those with medium (26%) or narrow (0%) AMPA as well as in those with high (44%) vs. low (10%) CoMiCs.
and on behalf of the FUTURE 1 study group Objective. To report the 5-year efficacy and safety of ... more and on behalf of the FUTURE 1 study group Objective. To report the 5-year efficacy and safety of secukinumab in the treatment of patients with psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326). Methods. Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab entered a 3-year extension phase. Results are presented for key efficacy endpoints for the secukinumab 150-mg group (n = 236), including patients who escalated from 150 to 300 mg (approved doses) starting at week 156. Safety is reported for all patients (n = 587) who received 1 dose or more of study treatment. Results. Overall, 81.8%% (193 of 236) of patients in the secukinumab 150-mg group completed 5 years of treatment, of which 36.4% (86 of 236) had dose escalation from 150 to 300 mg. Sustained improvements were achieved with secukinumab across all key efficacy endpoints through 5 years. Overall, 71.0%/51.8%/36.3% of patients achieved American College of Rheumatology (ACR) 20/50/70 responses at 5 years. Efficacy improved in patients requiring dose escalation from 150 to 300 mg and was comparable with those who did not require dose escalation. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years for any secukinumab dose were serious infections (1.8), Crohn's disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5). Conclusion. Secukinumab provided sustained improvements in the signs and symptoms in the major clinical domains of PsA. Efficacy improved for patients requiring dose escalation from 150 to 300 mg during the study. Secukinumab was well tolerated with no new safety signals.
Background: A specific subset of psoriasis patients is characterized by subclinical inflammatory ... more Background: A specific subset of psoriasis patients is characterized by subclinical inflammatory changes. These patients frequently present with arthralgia and have a higher risk to develop psoriatic arthritis (PsA). We hypothesized that IL-17A inhibition in this subset of patients can intercept the link between skin and joint disease and resolves pain and inflammatory changes. Methods: Psoriasis, but no PsA, patients were included in the open prospective exploratory Interception in very early PsA (IVEPSA) study. Patients had to have nail or scalp involvement or a high psoriasis area severity index (PASI) (> 6) as well as inflammatory or erosive changes in MRI or CT. Patients received treatment with the anti-interleukin (IL)-17A antibody secukinumab over 24 weeks. Clinical assessments of skin and joint disease were done at baseline and after 12 and 24 weeks, MRI and CT at baseline and after 24 weeks. Results: Twenty patients were included, 85% of them reporting arthralgia and 40% had tender joints at the examination. Eighty-three percent had at least one inflammatory lesion in the MRI, most of them synovitis/enthesitis. Skin disease (PASI: p < 0.002; BSA: p < 0.003) and arthralgia (VAS pain: p < 0.003) significantly improved after 24 weeks. Total PsAMRIS (p = 0.005) and synovitis subscore (p = 0.008) also significantly improved. Erosions and enthesiophytes did not progress, while bone mass in the distal radius significantly (p = 0.020) increased after 24 weeks. Conclusions: These data suggest that very early disease interception in PsA is possible leading to a comprehensive decline in skin symptoms, pain, and subclinical inflammation. IVEPSA therefore provides rationale for future early interventions with the concept to prevent the onset of PsA in high-risk individuals.
ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhib... more ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA).MethodsProspective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks.ResultsTOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers...
Background: Work is important to individuals and society. Given demographic changes, governments ... more Background: Work is important to individuals and society. Given demographic changes, governments have changed policy to encourage individuals to work to older ages. In the UK, the state pension age has been increased rapidly, especially amongst women. To date however, it is unclear whether people can continue to work into their late 60s in all types of work, particularly if they have musculoskeletal diagnoses with/without comorbidities. We explored the role of primary-care recorded musculoskeletal disorders in predicting health-related job loss over two years of follow-up in older adults. Methods: The Health and Employment After Fifty (HEAF) study is a cohort study of adults aged 50-64 years incepted 2013-14 from GP practices across England. Cohort participants completed annual questionnaires since baseline providing information about their work, health, finances, caring responsibilities and retirement intentions. Participants also granted written permission for us to obtain their detailed health information from the Clinical Practice Research Datalink. We used Cox's proportional hazards modelling to identify risk factors for time to first exit from a job mainly or partly for health related reasons between baseline and 2-year follow-up. Participants who remained in work or left work for reasons other than health were regarded as censored in the survival analysis. Results are reported as hazard ratios with 95% confidence intervals. Results: In total, 4,888 people provided information at baseline and at least one of the two follow-up questionnaires, were successfully linked with CPRD records, and were ever in paid work for at least 20 hours/ week during the 2-year follow-up. 277 people reported health-related job loss over the two years, 3,666 worked throughout and 945 left work not for health reasons. Amongst men, only one primary-care MSD diagnosis predicted health-related job loss: connective tissue disease (HR 5.1, 95% CI 1.5-17.1). However, amongst women, diagnoses of: widespread pain (HR 2.4, 95% CI 1.3-4.8); lower limb osteoarthritis (HR 2.3, 95% CI 1.4-3.7); upper limb surgery ever (HR 1.8, 95% CI0.9-3.8); and inflammatory arthritis (HR 2.1, 95% CI 1.2-3.6) were all independent predictors of health-related job loss and robust to adjustment for age, socioeconomic status, lifestyle factors, job satisfaction and coping with work's physical and mental demands. Conclusion: These findings suggest that musculoskeletal disorders contribute importantly to the risk of falling out of work before the age of eligibility for a state pension, particularly among female workers. To our knowledge, these gender effects have not been previously reported. If we are to retain older workers, it is important that we consider adjustments in the nature and type of work to support people with musculoskeletal disorders. This is particularly important amongst work forces in which women predominate such as health and social care.
Background: This post-hoc analysis investigated the link between acute phase reactant levels, pre... more Background: This post-hoc analysis investigated the link between acute phase reactant levels, prednisone doses, and giant cell arteritis (GCA) disease flares in the GiACTA trial (NCT01791153) as these have not been studied thoroughly in prospective clinical trials. Methods: Secondary analyses of prednisone doses, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) were performed for patients who experienced GCA flare after achieving remission during 52 weeks of treatment with TCZ-weekly or-everyother-week þ 26-week prednisone taper (TCZ-QW or TCZ-Q2W) or placebo þ 26-week or 52-week prednisone taper (PBOþ26 or PBOþ52). Analyses are descriptive and were performed post-hoc.
Objective. This study was undertaken to evaluate glucocorticoid dosages and serologic findings in... more Objective. This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. Methods. Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. Results. One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks. Conclusion. Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.
Seminars in arthritis and rheumatism, Jan 13, 2018
To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoria... more To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoriatic arthritis (PsA) patients with polyarticular disease. Specific studies on enthesitis are missing. IL-23 is considered to play a central role in the development of enthesitis. We therefore speculated that therapeutic inhibition of IL-12/IL-23 is particularly effective in enthesitis-driven PsA patients. Enthesial CLearance In PSoriatic Arthritis (ECLIPSA) is a prospective randomized-controlled open-label study. Patients with PsA with active enthesitis were randomized 1:1 to receive either ustekinumab (UST; arm 1) or tumor necrosis factor inhibitors (TNFi; arm 2). Primary endpoint was complete clearance of enthesitis, defined by Spondyloarthritis Research Consortium of Canada (SPARCC) index equal to zero at 24weeks. 51 patients (UST = 25; TNFi = 26) were screened, 47 enrolled (UST = 23; TNFi = 24) and 46 completed the study. Mean ± SD SPARCC index at baseline was 4.8 ± 2.6 in the UST gro...
Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly ... more Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce. In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DA...
Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bon... more Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of articular bone composition. In this study 476 subjects comprising healthy individuals and patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), ACPA-negative RA, Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO) and psoriatic arthritis (PsA) were subjected to high-resolution quantitative computed tomography (HR-pQCT) of the hand. Metacarpal heads were assessed for total, trabecular and cortical volumetric bone mineral density (vBMD). Only ACPA+RA, but not the remaining inflammatory diseases (ACPA-RA, CD, UC, PsO, PsA) showed significant (p < 0.001) loss of articular bone affecting both...
Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and l... more Objectives Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with MTX or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (P <0.001). PETVAS changes were numerically higher in patients receiving MTX (−12.3 units) or TOC (−11.7 uni...
Introduction: Hidradenitis suppurativa (HS) is a chronic, debilitating, and inflammatory skin dis... more Introduction: Hidradenitis suppurativa (HS) is a chronic, debilitating, and inflammatory skin disease. The epidemiology of HS varies greatly, with an estimated prevalence ranging from 0.03% to 4% worldwide. Similar to psoriasis (PsO), HS also exhibits a systemic inflammatory nature with a spectrum of systemic comorbidities. A large health insurance claims (HICs) database is analyzed to determine the demography and epidemiology of HS, PsO, and HS with concurrent PsO (HS-PsO) patients. Furthermore, the comorbidity profiles, including the comorbidity risk of these patient populations, are analyzed. Methods: This is a noninterventional retrospective analysis of anonymized HICs data using a subset of the Institute of Applied Health Research Berlin (InGef) database. The primary outcome is the prevalence and incidence of HS, PsO, and HS-PsO. Secondary outcomes include comorbidity profiles and a comorbidity risk analysis. Results: The prevalence and incidence of HS were 0.0681% and 0.0101%, respectively. The prevalence of HS-PsO was 0.004% (6% of the total HS population). HS patients frequently suffered from arterial hypertension (45%), nicotine dependence (46%), obesity (41%), and depression (36%), which were more common in HS-PsO patients compared with HS alone. HS patients had an increased prevalence of metabolic, psychiatric, immune-mediated, and cardiovascular diseases, e.g., overweight/obesity [odds ratio (OR): 2.65, 95% confidence interval (CI) 2.37-2.96], depression (OR: 1.55, 95% CI 1.42-1.76), or seronegative rheumatoid arthritis (OR: 2.82, 95% CI 1.61-4.94) compared with Digital Features To view digital features for this article go to
Background. Limited information exists about the very early forms of psoriatic arthritis. In part... more Background. Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reported outcomes (PROs) in very early as compared to established PsA have not been investigated to date.Methods. Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID) and global disease (VAS) in two small prospective observational studies on secukinumab 300mg over 6 months in very early disease patients (IVEPSA study; N=20) and established PsA (PSARTROS study; N=20). Cluster analysis was performed at baseline and 24-weeks follow-up.Results. While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-b...
Background. Limited information exists about the very early forms of psoriatic arthritis. In part... more Background. Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reportedoutcomes (PROs) in very early as compared to established PsA have not been investigated to date.Methods. Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID) and global disease (VAS) in two small prospective observational studies on secukinumab 300mg over 6 months in very early disease patients (IVEPSA study; N=20) and established PsA (PSARTROS study; N=20). Cluster analysis was performed at baseline and 24-weeks follow-up.Results. While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-be...
Objective. To assess if microstructural bone lesions in RA at-risk individuals are related to the... more Objective. To assess if microstructural bone lesions in RA at-risk individuals are related to the spectrum of anti-modified protein antibodies (AMPA) and affect the risk to develop RA. Methods. Cortical micro-channels (CoMiCs) as well as cortical and trabecular bone volumes were analyzed by high-resolution computed tomography in the hand joints of RA at-risk individuals. Anti-modified protein antibody (AMPA) response was profiled including reactivities against citrullinated proteins (vimentin, enolase, fibrinogen) as well as carbamylated and acetylated vimentin. All subjects were followed for the development of RA. Results. RA at-risk subjects (all N=74) with broad spectrum AMPA (6-8 reactivties) had significantly more severe microstructural changes (CoMiCs: 95±35/joint; total bone volume: 265±45 HA/cm3; trabecular bone volume: 176±42; cortical bone volume: 585±138) compared to subjects with moderate (3-5 reactivties; 79±30; 293±33; 195±32, 627±91, respectively) or narrow (1-2 reactivties; 47±20, 311±34, 211±30, 674±56, respectively) AMPA reactivity. Progressors to RA had significantly higher numbers of CoMiCs and lower bone volumes (CoMiCs: 103±30 vs. 71±35; total bone volume: 258±37 vs.295±34). Furthermore, progression to RA was high in subjects with broad (48%) vs. those with medium (26%) or narrow (0%) AMPA as well as in those with high (44%) vs. low (10%) CoMiCs.
and on behalf of the FUTURE 1 study group Objective. To report the 5-year efficacy and safety of ... more and on behalf of the FUTURE 1 study group Objective. To report the 5-year efficacy and safety of secukinumab in the treatment of patients with psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326). Methods. Following the 2-year core trial, eligible patients receiving subcutaneous secukinumab entered a 3-year extension phase. Results are presented for key efficacy endpoints for the secukinumab 150-mg group (n = 236), including patients who escalated from 150 to 300 mg (approved doses) starting at week 156. Safety is reported for all patients (n = 587) who received 1 dose or more of study treatment. Results. Overall, 81.8%% (193 of 236) of patients in the secukinumab 150-mg group completed 5 years of treatment, of which 36.4% (86 of 236) had dose escalation from 150 to 300 mg. Sustained improvements were achieved with secukinumab across all key efficacy endpoints through 5 years. Overall, 71.0%/51.8%/36.3% of patients achieved American College of Rheumatology (ACR) 20/50/70 responses at 5 years. Efficacy improved in patients requiring dose escalation from 150 to 300 mg and was comparable with those who did not require dose escalation. Exposure-adjusted incidence rates for selected adverse events per 100 patient-years for any secukinumab dose were serious infections (1.8), Crohn's disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5). Conclusion. Secukinumab provided sustained improvements in the signs and symptoms in the major clinical domains of PsA. Efficacy improved for patients requiring dose escalation from 150 to 300 mg during the study. Secukinumab was well tolerated with no new safety signals.
Background: A specific subset of psoriasis patients is characterized by subclinical inflammatory ... more Background: A specific subset of psoriasis patients is characterized by subclinical inflammatory changes. These patients frequently present with arthralgia and have a higher risk to develop psoriatic arthritis (PsA). We hypothesized that IL-17A inhibition in this subset of patients can intercept the link between skin and joint disease and resolves pain and inflammatory changes. Methods: Psoriasis, but no PsA, patients were included in the open prospective exploratory Interception in very early PsA (IVEPSA) study. Patients had to have nail or scalp involvement or a high psoriasis area severity index (PASI) (> 6) as well as inflammatory or erosive changes in MRI or CT. Patients received treatment with the anti-interleukin (IL)-17A antibody secukinumab over 24 weeks. Clinical assessments of skin and joint disease were done at baseline and after 12 and 24 weeks, MRI and CT at baseline and after 24 weeks. Results: Twenty patients were included, 85% of them reporting arthralgia and 40% had tender joints at the examination. Eighty-three percent had at least one inflammatory lesion in the MRI, most of them synovitis/enthesitis. Skin disease (PASI: p < 0.002; BSA: p < 0.003) and arthralgia (VAS pain: p < 0.003) significantly improved after 24 weeks. Total PsAMRIS (p = 0.005) and synovitis subscore (p = 0.008) also significantly improved. Erosions and enthesiophytes did not progress, while bone mass in the distal radius significantly (p = 0.020) increased after 24 weeks. Conclusions: These data suggest that very early disease interception in PsA is possible leading to a comprehensive decline in skin symptoms, pain, and subclinical inflammation. IVEPSA therefore provides rationale for future early interventions with the concept to prevent the onset of PsA in high-risk individuals.
ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhib... more ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA).MethodsProspective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks.ResultsTOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers...
Background: Work is important to individuals and society. Given demographic changes, governments ... more Background: Work is important to individuals and society. Given demographic changes, governments have changed policy to encourage individuals to work to older ages. In the UK, the state pension age has been increased rapidly, especially amongst women. To date however, it is unclear whether people can continue to work into their late 60s in all types of work, particularly if they have musculoskeletal diagnoses with/without comorbidities. We explored the role of primary-care recorded musculoskeletal disorders in predicting health-related job loss over two years of follow-up in older adults. Methods: The Health and Employment After Fifty (HEAF) study is a cohort study of adults aged 50-64 years incepted 2013-14 from GP practices across England. Cohort participants completed annual questionnaires since baseline providing information about their work, health, finances, caring responsibilities and retirement intentions. Participants also granted written permission for us to obtain their detailed health information from the Clinical Practice Research Datalink. We used Cox's proportional hazards modelling to identify risk factors for time to first exit from a job mainly or partly for health related reasons between baseline and 2-year follow-up. Participants who remained in work or left work for reasons other than health were regarded as censored in the survival analysis. Results are reported as hazard ratios with 95% confidence intervals. Results: In total, 4,888 people provided information at baseline and at least one of the two follow-up questionnaires, were successfully linked with CPRD records, and were ever in paid work for at least 20 hours/ week during the 2-year follow-up. 277 people reported health-related job loss over the two years, 3,666 worked throughout and 945 left work not for health reasons. Amongst men, only one primary-care MSD diagnosis predicted health-related job loss: connective tissue disease (HR 5.1, 95% CI 1.5-17.1). However, amongst women, diagnoses of: widespread pain (HR 2.4, 95% CI 1.3-4.8); lower limb osteoarthritis (HR 2.3, 95% CI 1.4-3.7); upper limb surgery ever (HR 1.8, 95% CI0.9-3.8); and inflammatory arthritis (HR 2.1, 95% CI 1.2-3.6) were all independent predictors of health-related job loss and robust to adjustment for age, socioeconomic status, lifestyle factors, job satisfaction and coping with work's physical and mental demands. Conclusion: These findings suggest that musculoskeletal disorders contribute importantly to the risk of falling out of work before the age of eligibility for a state pension, particularly among female workers. To our knowledge, these gender effects have not been previously reported. If we are to retain older workers, it is important that we consider adjustments in the nature and type of work to support people with musculoskeletal disorders. This is particularly important amongst work forces in which women predominate such as health and social care.
Background: This post-hoc analysis investigated the link between acute phase reactant levels, pre... more Background: This post-hoc analysis investigated the link between acute phase reactant levels, prednisone doses, and giant cell arteritis (GCA) disease flares in the GiACTA trial (NCT01791153) as these have not been studied thoroughly in prospective clinical trials. Methods: Secondary analyses of prednisone doses, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) were performed for patients who experienced GCA flare after achieving remission during 52 weeks of treatment with TCZ-weekly or-everyother-week þ 26-week prednisone taper (TCZ-QW or TCZ-Q2W) or placebo þ 26-week or 52-week prednisone taper (PBOþ26 or PBOþ52). Analyses are descriptive and were performed post-hoc.
Objective. This study was undertaken to evaluate glucocorticoid dosages and serologic findings in... more Objective. This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. Methods. Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. Results. One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks. Conclusion. Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.
Seminars in arthritis and rheumatism, Jan 13, 2018
To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoria... more To date, all studies addressing on anti-inflammatory drugs in PsA have been carried out in psoriatic arthritis (PsA) patients with polyarticular disease. Specific studies on enthesitis are missing. IL-23 is considered to play a central role in the development of enthesitis. We therefore speculated that therapeutic inhibition of IL-12/IL-23 is particularly effective in enthesitis-driven PsA patients. Enthesial CLearance In PSoriatic Arthritis (ECLIPSA) is a prospective randomized-controlled open-label study. Patients with PsA with active enthesitis were randomized 1:1 to receive either ustekinumab (UST; arm 1) or tumor necrosis factor inhibitors (TNFi; arm 2). Primary endpoint was complete clearance of enthesitis, defined by Spondyloarthritis Research Consortium of Canada (SPARCC) index equal to zero at 24weeks. 51 patients (UST = 25; TNFi = 26) were screened, 47 enrolled (UST = 23; TNFi = 24) and 46 completed the study. Mean ± SD SPARCC index at baseline was 4.8 ± 2.6 in the UST gro...
Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly ... more Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis (RA) treatment, but is poorly tolerated or contraindicated in some patients. There is a wealth of data supporting the use of abatacept in combination with MTX, but data on alternative conventional synthetic disease-modifying antirheumatic drug (csDMARD) combinations with abatacept are scarce. In this post-hoc exploratory analysis, efficacy and safety data were extracted from abatacept RA studies in which combination with csDMARDs other than MTX was permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real-world study (ACTION). Patients with moderate-to-severe RA received abatacept in combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or leflunomide for 6 months to 2 years according to the study design. Change from baseline in physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein) (DA...
Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bon... more Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now allow the accurate measure of articular bone composition. In this study 476 subjects comprising healthy individuals and patients with anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA), ACPA-negative RA, Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO) and psoriatic arthritis (PsA) were subjected to high-resolution quantitative computed tomography (HR-pQCT) of the hand. Metacarpal heads were assessed for total, trabecular and cortical volumetric bone mineral density (vBMD). Only ACPA+RA, but not the remaining inflammatory diseases (ACPA-RA, CD, UC, PsO, PsA) showed significant (p < 0.001) loss of articular bone affecting both...
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Papers by Juergen Rech