Anti-IL-6 Therapy Effect for Refractory Joint and Skin Involvement in Systemic Sclerosis: A Real-world, Single Center Experience

2021 ◽  
pp. jrheum.210273
Author(s):  
Stylianos T. Panopoulos ◽  
Maria G. Tektonidou ◽  
Vasiliki-Kalliopi Bournia ◽  
Aikaterini Arida ◽  
Petros P. Sfikakis
Keyword(s):  
Systemic Sclerosis ◽  
Real World ◽  
Disease Duration ◽  
Retention Rates ◽  
Skin Involvement ◽  
Hematopoietic Stem ◽  
Single Center Experience ◽  
Therapy Effect ◽  
Patient Reported

Objective To examine the efficacy and safety of interleukin-6 inhibition by tocilizumab in difficult-to-treat real-world patients with Systemic Sclerosis (SSc). Methods Twenty-one patients [20 women, 16 diffuse SSc, mean age: 52±10 years, 10 with early (<5 years) and 11 with long-standing disease (mean disease duration: 6.4±3.7 years)] with active joint and/or skin involvement refractory to corticosteroids (n=21), methotrexate (n=19), cyclophosphamide (n=10), mycophenolate (n=7), rituximab (n=1), leflunomide (n=2), hydroxychloroquine (n=2), and hematopoietic stem cell transplantation (n=2) who received weekly tocilizumab (162 mg subcutaneously) in an academic center, were monitored prospectively. Changes in modified Rodnan skin score (mRSS), disease activity score (DAS)28, lung function tests (LFTs) and patient reported outcomes (PROs) were analyzed after one year of treatment and at follow-up end. Results One patient discontinued tocilizumab after 3 months due to inefficacy. During the first year of treatment, improvement was evident in the remaining 20 patients regarding skin involvement (mean mRSS change: -6.9±5.9,p<0.001), polyarthritis (mean DAS28 change: -1.9±0.8,p<0.001) and PROs (all p<0.001); LFTs stabilization was observed in 16/20 patients. During the second year, 3 patients discontinued tocilizumab (cytomegalovirus infection in 1, inefficacy in 2) and one died. Beneficial effects were sustained in all 16 patients at follow-up end (2.2±1.1 years), except LFTs deterioration in 3. Apart from recurrent digital ulcer infection in 3 patients, tocilizumab was well-tolerated. Conclusion Tocilizumab was effective in refractory joint and skin involvement irrespective of SSc disease duration or subtype. Long-term retention rates and disease stabilization for most real-world patients suggest that tocilizumab might be a valuable choice for difficult-to-treat SSc.

scholarly journals Hematopoietic stem cell transplantation for systemic sclerosis: Brazilian experience

2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Álvaro Henrique-Neto ◽  
Marianna Yumi Kawashima Vasconcelos ◽  
Juliana Bernardes Elias Dias ◽  
Daniela Aparecida de Moraes ◽  
Maynara Santana Gonçalves ◽  
...  
Keyword(s):  
Stem Cell ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Skin Involvement ◽  
Hematopoietic Progenitor ◽  
Post Transplantation ◽  
Hematopoietic Stem

Abstract Background In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan’s skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results Median (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud’s disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

P124 COMPARISONS OF HOLISTIC PATIENT-REPORTED OUTCOMES BY BIOLOGIC DRUG CLASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A REAL-WORLD STUDY IN IBD PARTNERS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S23-S24
Author(s):  
Millie Long ◽  
Xian Zhang ◽  
Wenli Chen ◽  
Trevor Lissoos
Keyword(s):  
Real World ◽  
Patient Reported Outcomes ◽  
Drug Class ◽  
Disease Duration ◽  
Pain Interference ◽  
Longitudinal Analyses ◽  
Social Satisfaction ◽  
Patient Reported ◽  
Anxiety Depression

Abstract Background Increasing numbers of biologic agents are now available for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data are available on clinical characteristics of populations initiating these therapies and relevant holistic patient-reported outcomes (PROs) in the real-world. Methods We used data from IBD Partners from May 2014-May 2019. Individuals initiating an anti-tumor necrosis factor (anti-TNF) agent or vedolizumab (VDZ) were included. A subgroup with at least 6 months of follow-up who had baseline data within 90 days of therapy initiation were included in longitudinal analyses. We aimed to: 1) compare clinical characteristics of patients initiating each biologic therapy and 2) compare PROs at follow-up by drug class. Outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) T scores for anxiety, depression, fatigue, pain interference, and social satisfaction. We used logistic regression models controlling for prior biologic exposure, age, sex, prior hospitalization, disease duration, surgery (for CD), and baseline values of each PRO to compare PROs at follow-up by drug class. Levels of each PRO within a half standard deviation of the general population T score represented wellness. Results A total of 878 patients initiating anti-TNF (625 CD, 253 UC) and 651 initiating VDZ (415 CD, 236 UC) were included. Patients with CD initiating VDZ were more likely to be older, had longer disease duration, increased IBD-related hospitalization, more prior surgeries, and were more likely to be biologic exposed (P&lt;0.05 for all). Patients with UC initiating VDZ were more likely to be male and biologic exposed (P&lt;0.05 for both) (Table 1). In longitudinal analyses, a total of 198 patients on anti-TNF and 168 on VDZ were included for CD; a total of 85 on anti-TNF and 96 on VDZ were included for UC. Individuals with CD initiating VDZ had significantly greater fatigue, pain interference, and reduced social satisfaction at baseline compared with the anti-TNF population. For UC, PROs at baseline were similar across drug groups. In both CD and UC, there were no significant differences in adjusted odds of wellness for each PRO at follow-up by drug class (Table 2). Conclusions CD patients initiating VDZ in this real-world cohort had multiple factors consistent with more severe disease compared with those initiating anti-TNF. In longitudinal analyses after at least 6 months of treatment with VDZ or anti-TNF, there were no differences in wellness of PROs, such as anxiety, depression, fatigue, pain interference, or social satisfaction by drug class for CD or UC.

Effectiveness of Dulaglutide in the Real World and in Special Populations of Type 2 Diabetic Patients

2020 ◽  
Vol 105 (7) ◽  
pp. e2617-e2625 ◽  
Author(s):  
Mario Luca Morieri ◽  
Vera Frison ◽  
Mauro Rigato ◽  
Michele D’Ambrosio ◽  
Federica Tadiotto ◽  
...  
Keyword(s):  
Body Weight ◽  
Real World ◽  
Disease Duration ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Body Weight Reduction ◽  
Background Population ◽  
Glucagon Like Peptide 1

Abstract Context In randomized controlled trials (RCTs) on type 2 diabetes (T2D) patients, the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-RA) dulaglutide reduced HbA1c and body weight, but generalizability of such findings to real-world T2D patients is challenging. Objective We evaluated effectiveness of dulaglutide in routine clinical practice, especially in subgroups of patient that are underrepresented in RCTs. Design Retrospective multicenter study. Setting Diabetes outpatient clinics. Patients and intervention All consecutive patients who initiated dulaglutide between 2015 and 2018. Main outcome measures Changes in HbA1c and body weight were assessed up to 30 months after baseline. Effectiveness was analyzed in patient subgroups according to: prior use of GLP-1RA, persistence on treatment and dose, age, sex, disease duration, renal function, obesity, cardiovascular disease, or concomitant use of insulin or sulphonylurea. Results From a background population of 83,116 patients, 2084 initiated dulaglutide (15.3% switching from another GLP-1RA), 1307 of whom had at least 1 follow-up visit. Overall, dulaglutide reduced HbA1c by 1.0% and body weight by 2.9 kg at the end of observation. These effects were more pronounced in GLP-1RA-naïve patients and in those with shorter disease duration. Improvement in HbA1c was highly significant and consistent across all subgroups, including those aged ≥ 75 years, nonobese, or with chronic kidney disease. Body weight declined in all subgroups and significantly more with the 1.5-mg versus 0.75-mg dose. Conclusions In real-world T2D patients, effectiveness of dulaglutide on HbA1c and body weight reduction was highly consistent and significant even in subgroups of patients poorly represented in RCTs.

scholarly journals Real-World Outcomes of Ivacaftor Treatment in People with Cystic Fibrosis: A Systematic Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1527
Author(s):  
Jamie Duckers ◽  
Beth Lesher ◽  
Teja Thorat ◽  
Eleanor Lucas ◽  
Lisa J. McGarry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cystic Fibrosis ◽  
Real World ◽  
Safety Profile ◽  
Clinical Trial Data ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Patient Reported ◽  
Clinical Benefits

Cystic fibrosis (CF) is a rare, progressive, multi-organ genetic disease. Ivacaftor, a small-molecule CF transmembrane conductance regulator modulator, was the first medication to treat the underlying cause of CF. Since its approval, real-world clinical experience on the use of ivacaftor has been documented in large registries and smaller studies. Here, we systematically review data from real-world observational studies of ivacaftor treatment in people with CF (pwCF). Searches of MEDLINE and Embase identified 368 publications reporting real-world studies that enrolled six or more pwCF treated with ivacaftor published between January 2012 and September 2019. Overall, 75 publications providing data from 57 unique studies met inclusion criteria and were reviewed. Studies reporting within-group change for pwCF treated with ivacaftor consistently showed improvements in lung function, nutritional parameters, and patient-reported respiratory and sino-nasal symptoms. Benefits were evident as early as 1 month following ivacaftor initiation and were sustained over long-term follow-up. Decreases in pulmonary exacerbations, Pseudomonas aeruginosa prevalence, and healthcare resource utilization also were reported for up to 66 months following ivacaftor initiation. In studies comparing ivacaftor treatment to modulator untreated comparator groups, clinical benefits similarly were reported as were decreases in mortality, organ-transplantation, and CF-related complications. The safety profile of ivacaftor observed in these real-world studies was consistent with the well-established safety profile based on clinical trial data. Our systematic review of real-world studies shows ivacaftor treatment in pwCF results in highly consistent and sustained clinical benefit in both pulmonary and non-pulmonary outcomes across various geographies, study designs, patient characteristics, and follow-up durations, confirming and expanding upon evidence from clinical trials.

The Association Between Disease Activity and Duration in Systemic Sclerosis

2010 ◽  
Vol 37 (11) ◽  
pp. 2299-2306 ◽  
Author(s):  
JENNIFER G. WALKER ◽  
RUSSELL J. STEELE ◽  
MIREILLE SCHNITZER ◽  
SUZANNE TAILLEFER ◽  
MURRAY BARON ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Disease Activity ◽  
Disease Duration ◽  
Activity Index ◽  
Disease Onset ◽  
Depression Scale ◽  
Disease Activity Index ◽  
Cross Sectional ◽  
Diffuse Disease ◽  
Patient Reported

Objective.The absence of a standardized disease activity index has been an important barrier in systemic sclerosis (SSc) research. We applied the newly derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of patients with SSc to document changes in disease activity over time and to assess possible differences in activity between limited and diffuse disease.Methods.Cross-sectional study of a national cohort of patients enrolled in the Canadian Scleroderma Research Group Registry. Disease activity was measured using the SDAI. Depression scores were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D).Results.A total of 326 out of 639 patients had complete datasets at the time of this analysis; 87% were female, of mean age 55.6 years, with mean disease duration 14.1 years. SDAI declined steeply in the first 5 years after disease onset and patients with diffuse disease had 42% higher SDAI scores than patients with limited disease with the same disease duration and depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients with higher CES-D scores had higher SDAI scores relative to patients with the same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14, 1.31). Among the 10 components that make up the SDAI, only skin score (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely to be present in patients with diffuse disease. High depression scores were associated with positive responses for patient-reported changes in skin and cardiopulmonary function.Conclusion.Disease activity declined with time and patients with diffuse disease had consistently higher SDAI scores. Depression was found to be associated with higher patient activity scores and strongly associated with patient self-response questions. The role of depression should be carefully considered in future applications of the SDAI, particularly as several components of the score rely upon patient recall.

O24 Concomitant treatment with MTX does not increase the efficacy of ustekinumab or TFNi in PsA: results from the PsABio study

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Stefan Siebert ◽  
Elisa Gremese ◽  
Paul Bergmans ◽  
Kurt de Vlam ◽  
Beatriz Joven-Ibáñez ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Concomitant Treatment ◽  
Skin Involvement ◽  
Research Support ◽  
Real World Data ◽  
Low Disease Activity ◽  
Intention To Treat ◽  
Patient Reported

Abstract Background The additional benefit of methotrexate (MTX) as a concomitant treatment in PsA has not been fully elucidated for TNF inhibitors (TNFi) and no real-world data on this currently exist for ustekinumab (UST). We investigated the additive effect of MTX on the ability to reach composite treatment targets beyond monotherapy with UST or TNFi, and the ability to improve patient-reported outcomes in a real-world clinical setting in 8 European countries. Methods The PsABio study (NCT02627768) evaluates persistence, effectiveness and tolerability of 1st, 2nd or 3rd-line UST or TNFi in patients with PsA. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (LDA) or remission, as well as the patient acceptable symptom state (PASS; score ≤4) of the 12-item Psoriatic Arthritis Impact of Disease questionnaire (PsAID-12) were evaluated. Here we present 6-month follow-up data using intention to treat (ITT) analysis; patients who stopped/switched initial treatment were imputed as non-responders. The effect of MTX co-therapy was investigated within UST and TNFi cohorts, as well as between the cohorts, using multivariate logistic regression including interaction terms, and propensity score (PS) analysis to adjust for imbalanced, potentially prognostic, baseline covariates. Results Of 930 patients, data was available for 868 ITT patients, including patients who switched/stopped before 6 months (UST: n = 28/426 [6.6%], TNFi: n = 44/442 [10.0%]). At baseline there were no relevant differences in demographics and disease activity, however there were significant differences in skin involvement as well as csDMARD and NSAID exposure. Co-therapy with MTX did not increase the likelihood of achieving any of the outcomes in either the UST or TNFi cohorts (Table 1). After PS adjustment, co-treatment with MTX did not influence treatment effects differently when added to UST compared with TNFi. concomitant use of csDMARDs other than MTX yielded very similar results. Conclusion In a real-world setting, concomitant treatment with MTX in addition to UST or TNFi was not associated with enhanced effects across a broad variety of disease outcomes, including disease activity, disease impact, and skin involvement within or between treatment cohorts, after PS adjustment for baseline confounders. Disclosures S. Siebert: Consultancies; AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, Novartis. Grants/research support; Pfizer, Janssen, BMS, Celgene, UCB, Boehringer Ingelheim. E. Gremese: Consultancies; AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, Pfizer. P. Bergmans: Shareholder/stock ownership; Johnson & Johnson. Other; Employee of Janssen. K. de Vlam: Consultancies; Johnson & Johnson. B. Joven-Ibáñez: Member of speakers’ bureau; Celgene, Novartis, MSD, Pfizer, AbbVie, Janssen. G. Katsifis: None. T.V. Korotaeva: Consultancies; Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, UCB, Lilly, Novartis-Sandoz. W. Noël: Other; Employee of Janssen. C. Selmi: None. P.P. Sfikakis: None. P. Smirnov: Other; Employee of Janssen. E. Theander: Other; Employee of Janssen. M.T. Nurmohamed: Grants/research support; Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Lilly, Sanofi, Celgene. L. Gossec: Honoraria; AbbVie, Celgene, Janssen, Lilly, Novartis-Sandoz, Pfizer, Sanofi, UCB. Grants/research support; Pfizer. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, GlaxoSmithKline, ILTOO Pharma, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. Grants/research support; AbbVie, Janssen, Lilly, MSD, Pfizer, Roche.

scholarly journals High frequency ultrasound of skin involvement in systemic sclerosis – a follow-up study

2015 ◽  
Vol 17 (1) ◽  
Author(s):  
Roger Hesselstrand ◽  
Johanna Carlestam ◽  
Marie Wildt ◽  
Gunnel Sandqvist ◽  
Kristofer Andréasson
Keyword(s):  
Systemic Sclerosis ◽  
High Frequency ◽  
Skin Involvement ◽  
High Frequency Ultrasound ◽  
Follow Up Study ◽  
Frequency Ultrasound

Real-world examination of remission patterns in patients (pts) with acute myeloid leukemia (AML).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19336-e19336
Author(s):  
Ashley Tabah ◽  
David Huggar ◽  
Brenna L. Brady ◽  
Krutika Jariwala-Parikh ◽  
Ronda Copher ◽  
...  
Keyword(s):  
Median Time ◽  
Real World ◽  
Healthcare Resource Utilization ◽  
Administrative Claims ◽  
Hematopoietic Stem ◽  
Diagnosis Codes ◽  
First Remission ◽  
First Relapse ◽  
Frontline Therapy

e19336 Background: For pts with AML, prognosis is poor as long-term remission is elusive and ≥ 60% of pts relapse. The effect of remission status on healthcare resource utilization (HCRU) and costs is unclear. This study assessed administrative claims data from pts with AML to understand the potential benefit of novel, remission-prolonging therapies on HCRU and costs. Methods: Pts with newly diagnosed AML who received frontline therapy and did not undergo hematopoietic stem cell transplantation were identified in the MarketScan Commercial and Medicare Supplemental database from Jan 1, 2012–June 6, 2018. Pts were followed over a fixed 6-month (mos) pre- and variable post-diagnosis period; remission and relapse events were identified by diagnosis codes. Pts were analyzed by duration of remission ( < 3, 3– < 6, 6– < 9, and ≥ 9 mos), based on time from first remission claim to first relapse claim or end of follow up, whichever occurred first. Pt characteristics, relapse, HCRU, and costs were assessed. Results: 459/1003 eligible pts (45.8%) had evidence of remission. Most pts were in remission for < 3 mos (n = 161; 35.1%) or ≥ 9 mos (n = 165; 35.9%); 81 (17.6%) and 52 (11.3%) pts were in remission for 3– < 6 and 6– < 9 mos, respectively. Median follow-up for all pts was 236 days. Across remission cohorts, mean age at diagnosis was 55–59 years and median time to remission (from first AML diagnosis to first remission claim) was 82–90 days. Median time from AML diagnosis to relapse was 265.5 days. Of pts in remission, 30.5% relapsed (41.0%, 28.4%, 40.4%, and 18.2% for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). From AML diagnosis to the end of follow-up, mean all-cause per pt per mos (PPPM) healthcare costs for all pts were $44,588. Longer durations of remission were associated with reduced mean PPPM costs ($64,188, $53,260, $30,219, and $16,654 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively); similar trends were observed for AML-related costs. Mean all-cause PPPM costs were also reduced during remission, measured from the first remission claim to the first relapse claim or end of follow-up. A significant decrease was observed for pts in remission for ≥ 6 mos ($35,229, $36,193, $17,486, and $8,933 for < 3, 3– < 6, 6– < 9, and ≥ 9 mos, respectively). Conclusions: In this real-world study, 46% of pts with AML achieved remission after frontline therapy, although durations of remission varied. A longer duration of remission was associated with reduced PPPM costs over the study period indicating a potential economic benefit of remission-prolonging therapies in AML, including maintenance treatments.

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