scholarly journals PERsistent Sitagliptin treatment & Outcomes (PERS&O 2.0) study, long-term results: a real-world observation on DPP4-inhibitor effectiveness

2020 ◽  
Vol 8 (1) ◽  
pp. e001507
Author(s):  
Antonio Carlo Bossi ◽  
Valentina De Mori ◽  
Carlotta Galeone ◽  
Davide Pietro Bertola ◽  
Margherita Gaiti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Real World ◽  
Repeated Measures ◽  
Long Term Results ◽  
Italian Population ◽  
Drug Survival ◽  
Kaplan Meier ◽  
Significant Difference

IntroductionSitagliptin is a dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes (T2D). Limited real-world data on its effectiveness and safety are available from an Italian population.Research design and methodsWe evaluated long-term clinical data from the single-arm PERsistent Sitagliptin Treatment & Outcomes (PERS&O) study, which collected information on 440 patients with TD2 (275 men, 165 women; mean age 64.1 years; disease median duration: 12 years) treated with sitagliptin ‘add-on’. For each patient, we estimated the 10-year cardiovascular (CV) risk using the UK Prospective Diabetes Study (UKPDS) Risk Engine (RE). Drug survival was evaluated using Kaplan-Meier survival curves; repeated measures mixed effects models were used to evaluate the evolution of glycated hemoglobin (HbA1c) and CV risk during sitagliptin treatment.ResultsAt baseline, most patients were overweight or obese (median body mass index (BMI) (kg/m2) 30.2); median HbA1c was 8.4%; median fasting plasma glucose: 172 mg/dL; median UKPDS RE score: 24.8%, being higher in men (median 30.2%) than in women (median 17.0%) as expected. Median follow-up from starting sitagliptin treatment was 5.6 years. From Kaplan-Meier curves, the estimated median drug survival was 32.8 months when considering discontinuation for any cause and 58.4 months when considering discontinuation for loss of efficacy. A significant improvement in HbA1c was evident during treatment with sitagliptin (p<0.01): the reduction was rapid (median HbA1c after 4–6 months: 7.5%) and continued at longer follow-up. When comparing patients treated with sitagliptin versus those stopping sitagliptin and switching to another antihyperglycemic drug, we detected a significant difference in the evolution of HbA1c in favor of patients who continued sitagliptin treatment. The UKPDS RE score at 10 years and the BMI significantly improved during treatment with sitagliptin (p<0.001). Adverse events were relatively uncommon.ConclusionPatients with T2D treated with sitagliptin achieved an improvement in metabolic control and a reduction in CV risk and did not experience relevant adverse events.

Long-term results and comparison of flow re-direction endoluminal device and pipeline embolization device in endovascular treatment of intracranial carotid aneurysms

2021 ◽  
pp. 159101992110307
Author(s):  
Cemal A Gündoğmuş ◽  
Soheil Sabet ◽  
Nurten A Baltacıoğlu ◽  
Derya Türeli ◽  
Yaşar Bayri ◽  
...  
Keyword(s):  
Adverse Events ◽  
Treatment Success ◽  
Long Term Results ◽  
Pipeline Embolization Device ◽  
Mortality And Morbidity ◽  
Significant Difference ◽  
Aneurysm Occlusion ◽  
Carotid Aneurysms

Objective This study aims to compare the efficacy, safety, and long-term outcomes of two flow diverters, i.e., pipeline embolization device and flow re-direction endoluminal device, in the treatment of distal carotid aneurysms. Methods A total of 138 patients with 175 aneurysms were included from February 2012 to September 2019. Ninety-nine aneurysms were treated with flow re-direction endoluminal device and 76 with pipeline embolization device. Angiographic follow-ups were at the 6th, 12th, 24th, 36th, and 60th months; the O’Kelly-Marotta grading scale was used to assess aneurysms occlusion. Outcomes of two devices were compared; possible associations regarding patient characteristics, aneurysm properties, treatment details, and adverse events were evaluated. Results The mean follow-up period was 33 months, with 10 patients lost to follow-up. Occlusion rates at the 6th and 12th months and during the last follow-up were similar for flow re-direction endoluminal device (81%, 84%, and 90%) and pipeline embolization device (82%, 85%, and 93%). Occlusion rates were also similar after stand-alone use without coiling. There was no significant difference regarding adverse event rates with a 10.9% overall complication rate, 3.6% mortality, and 0.7% permanent morbidity. All the mortality and morbidity were related to hemorrhagic complications. Device deployment failure was observed with five flow re-direction endoluminal devices and two pipeline embolization devices, whereas two severe in-stent stenoses occurred with each device. Conclusions Both flow re-direction endoluminal device and pipeline embolization device are feasible and effective in flow diversion of distal internal carotid artery aneurysms, with similar adverse events rates and aneurysm occlusion success. Aneurysm occlusion rates increase with time, while the presence of an integrated branch significantly decreases treatment success.

Long-Term Results of Total Hip Arthroplasty with the Cementless Spotorno (CLS) System

2017 ◽  
Vol 27 (5) ◽  
pp. 465-471 ◽  
Author(s):  
Christiaan Smeekes ◽  
Pieter B. de Witte ◽  
Bas F. Ongkiehong ◽  
Bart C.H. van der Wal ◽  
Alexander F.W. Barnaart
Keyword(s):  
Total Hip Arthroplasty ◽  
Hip Arthroplasty ◽  
Repeated Measures ◽  
Long Term Results ◽  
Factors Associated ◽  
Total Hip ◽  
Kaplan Meier ◽  
Age At Surgery

Background This study presents the long-term results of the Cementless Spotorno (CLS) total hip arthroplasty system and an analysis of factors associated with clinical and radiographic outcome. Methods We studied a series of 120 consecutive CLS arthroplasties in a young patient group (mean age at surgery: 55.9 ± 5.9 years). The Merle d'Aubigné-Postel score, polyethylene (PE) wear, and radiographic status were recorded during follow-up. Survival analyses, repeated-measures analysis of variance, and a nested case-control study were used for statistical evaluation. Results After a mean follow-up of 14.6 years (range 0.1-24.2 years, including revisions and lost to follow-up), 24 revisions had been performed, 16 of which for aseptic cup loosening. Kaplan-Meier survival analysis showed a 24-year survival of 72.8% (95% CI, 63.0%-82.6%) with revision for any reason as endpoint, and 80.1% (95% CI, 70.9%-89.3%) for revision for aseptic cup loosening. Mean final Merle d'Aubigné-Postel score was 16.1 points (range 7-18). Mean PE wear at final follow-up was 2.3 mm (range 0.6-6.8 mm). A higher rate of PE wear was associated with better clinical scores but also with revision for cup loosening. Factors associated with more PE wear were: younger age at surgery; 32 - mm head; longer follow-up; and steeper inclination angle. Conclusions Beyond 10 years, the CLS stem is reliable, but the high revision rate for aseptic cup loosening is concerning, specifically with better performing (cementless) alternatives available.

scholarly journals 13-year Follow-up of Treatment of Osteochondral Lesions with MACI

2019 ◽  
Vol 4 (4) ◽  
pp. 2473011419S0004 ◽  
Author(s):  
Chris Kreulen ◽  
Trevor Shelton ◽  
Jacqueline Nguyen ◽  
Eric Giza ◽  
Martin Sullivan
Keyword(s):  
Social Functioning ◽  
Physical Functioning ◽  
Bodily Pain ◽  
Long Term Results ◽  
Osteochondral Lesions ◽  
Sf 36 ◽  
Significant Difference ◽  
And Function

Category: Ankle, Arthroscopy, Hindfoot, Sports, Trauma Introduction/Purpose: Surgical management of osteochondral lesions of the talus (OLT) present an ongoing treatment challenge. Previously, matrix-induced autologous chondrocyte implantation (MACI) demonstrated improved pain and function at 7-years postoperative, providing evidence that MACI is a reliable method for treating cartilage. However, it is unknown the long- term results of MACI in OLT. The purpose of this study was to assess 13-year clinical follow-up data and the long-term success of this implant by comparing patient reported outcome measures (PROMs) pre-operatively, at 7-years post-operative, and at 13- years post-operative. Methods: A prospective investigation of MACI was performed on 10 patients with OLTs who had failed previous arthroscopic treatment. Of the 10 patients, 9 were available for 7-year and 13-year follow-up. Short Form Health Survey (SF-36) and the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot evaluation were utilized at pre-operative, 7-year, a 13-year postoperative. For each patient, a paired t-test was used to compare 13-year post-operative PROMs to pre-operative PROMs. A single factor analysis of variance (ANOVA) determined whether PROMs were different between pre-operative, 7-year post- operative, and 13-year post-operative time intervals. When a significant difference was detected, a post-hoc Tukey’s determined which time periods were different. Results: SF-36 data at 13-years showed significant improvements in Physical Functioning (p=0.012), Lack of Bodily Pain (p=0.017), and Social Functioning (p=0.007) compared with preoperative data. There were no differences in other components of the SF-36 outcomes (p>0.05). Although the AOFAS was on average 12 points higher at 13-years postoperative, this was not statistically significant (p=0.173). As for comparing PROMs over time, 13-years post-operative PROMs were comparable to 7-years post- operative (Table 1). There were better PROMs for Physical Functioning, Bodily Pain, and Social Functioning at 7- and 13-years post-operative compared to pre-operative while Physical Role Functioning was also better at 7-years post-operative compared to pre-operative. Conclusion: This study shows MACI provides greater pain relief and function at 13-years post-operative with stable long-term follow-up. MACI should be considered for osteochondral lesions that fail initial microfracture.

Long-term functional outcomes of different subtypes of primary congenital glaucoma

2019 ◽  
pp. bjophthalmol-2019-315131 ◽  
Author(s):  
Richard Sher Chaudhary ◽  
Amisha Gupta ◽  
Ajay Sharma ◽  
Shikha Gupta ◽  
Rayees Ahmad Sofi ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Congenital Glaucoma ◽  
Cumulative Probability ◽  
Primary Congenital Glaucoma ◽  
Visual Outcomes ◽  
Post Surgery ◽  
Kaplan Meier ◽  
Significant Difference

AimTo analyse long-term visual outcomes across different subtypes of primary congenital glaucoma (PCG).MethodsPatients with PCG with a minimum of 5-year follow-up post surgery were included in the study. Snellen visual acuity recordings taken at their last follow-up were analysed. We evaluated the results using Kaplan-Meier curves to predict the probability of maintaining good vision (as defined by a visual acuity of 6/18 or better) in our patients after 30-year follow-up. The results were also analysed to determine whether there were any differences in the long-term visual acuities with time between the neonatal and infantile PCG. We also analysed the reasons for poor visual outcomes.ResultsWe assessed a cohort of 140 patients with PCG (235 eyes) with an average follow-up of 127±62.8 months (range 60–400 months). Overall, the proportion of eyes with good visual acuity was 89 (37.9%), those with fair visual acuity between 6/60 and 6/18 was 41 (17.4%), and those with poor visual acuity (≤6/60) was 105 (44.7%). We found a significant difference (p=0.047) between neonatal and infantile patients with PCG whereby the neonatal cohort fared worse off in terms of visual morbidity. On Kaplan-Meier analysis, the cumulative probability of survival of a visual acuity of 6/18 or better was more among the infantile PCG in comparison to the neonatal PCG (p=0.039) eyes, and more among the bilateral than the unilateral affected eyes (p=0.029). Amblyopia was the most important cause for poor visual acuity as shown on a Cox proportional-hazards regression model .ConclusionsLong-term visual outcomes of infantile are better than neonatal PCG. Eyes with unilateral have worse visual outcomes compared with those with bilateral PCG because of the development of dense amblyopia.

Reinforcement Rings for Deficient Acetabular Bone in Revision Surgery: Long-Term Results

1997 ◽  
Vol 7 (2) ◽  
pp. 57-64 ◽  
Author(s):  
E. Garcia-Cimbrelo ◽  
J. Alonso-Biarge ◽  
J. Cordero-Ampuero
Keyword(s):  
Revision Surgery ◽  
Clinical Results ◽  
Long Term Results ◽  
Cumulative Probability ◽  
Metal Ring ◽  
Kaplan Meier ◽  
Medial Migration ◽  
Cemented Cup

This study analyzes the long-term results of 23 metal ring supports used in revision surgery since 1979. Only a metallic ring and a cemented cup were used in this series. Bone grafts and cementless cups were excluded from this study. One deep infection was excluded from the follow-up study. In the 22 cases analyzed, the mean follow-up period was 10 years for all cases and 12.2 years for unrevised cases. Bone defects according to the AAOS classification were: Grade 1, 1 case, Grade 2, 1 case, Grade 3, 10 cases, and Grade 4, 10 cases. A Müller ring was indicated in an anterior or medial wall defect (12 cases) and a Burch-Schneider ring was indicated in an anterior or posterior column defect or in pelvic discontinuity (10 cases). The clinical results were good in 8 cases, fair in 8 cases, and poor in 6 cases. Six cases were rerevised or removed, resulting in a total cumulative probability of rerevison or removal of 23.8% after 10 years according to the Kaplan-Meier analysis. Postoperatively, 18 cases had neutral rings, 2 cases had horizontal rings, and 2 cases had vertical rings. Radiological cup migration was found in 12 cases, resulting in a total cumulative probability of migration of 56.8% after 13 years according to the Kaplan-Meier analysis. Changes in the acetabular angle were present in 2 cases, vertical migration in 12 cases, and medial migration in 10 cases. Our data suggest that the metal ring and cemented cup alone could be used for salvage surgery in elderly patients and in low-demand patients. Possibly, adding bone graft could improve these results.

Early clinical results of minimally invasive coracoclavicular ligament reconstruction can be maintained at a minimum of five years’ follow-up

2020 ◽  
Vol 102-B (7) ◽  
pp. 918-924
Author(s):  
Steffen B. Rosslenbroich ◽  
Katharina Heimann ◽  
Jan Christoph Katthagen ◽  
Clemens Koesters ◽  
Oliver Riesenbeck ◽  
...  
Keyword(s):  
Minimally Invasive ◽  
Constant Score ◽  
Clinical Results ◽  
Long Term Results ◽  
Short Term ◽  
Ac Joint ◽  
Ac Joint Dislocation ◽  
Significant Difference

Aims There is a lack of long-term data for minimally invasive acromioclavicular (AC) joint repair. Furthermore, it is not clear if good early clinical results can be maintained over time. The purpose of this study was to report long-term results of minimally invasive AC joint reconstruction (MINAR) and compare it to corresponding short-term data. Methods We assessed patients with a follow-up of at least five years after minimally invasive flip-button repair for high-grade AC joint dislocation. The clinical outcome was evaluated using the Constant score and a questionnaire. Ultrasound determined the coracoclavicular (CC) distance. Results of the current follow-up were compared to the short-term results of the same cohort. Results A total of 50 patients (three females, 47 males) were successfully followed up for a minimum of five years. The mean follow-up was 7.7 years (63 months to 132 months). The overall Constant score was 94.4 points (54 to 100) versus 97.7 points (83 to 100) for the contralateral side showing a significant difference for the operated shoulder (p = 0.013) The mean difference in the CC distance between the operated and the contralateral shoulder was 3.7 mm (0.2 to 7.8; p = 0.010). In total, 16% (n = 8) of patients showed recurrent instability. All these cases were performed within the first 16 months after introduction of this technique. A total of 84% (n = 42) of the patients were able to return to their previous occupations and sport activities. Comparison of short-term and long-term results revealed no significant difference for the Constant Score (p = 0.348) and the CC distance (p = 0.974). Conclusion The clinical outcome of MINAR is good to excellent after long-term follow-up and no significant differences were found compared to short-term results. We therefore suggest this is a reliable technique for surgical treatment of high-grade AC joint dislocation. Cite this article: Bone Joint J 2020;102-B(7):918–924.

scholarly journals Transpancreatic biliary sphincterotomy for biliary access is safe also on a long-term scale

2020 ◽  
Vol 35 (1) ◽  
pp. 104-112
Author(s):  
Vilja Koskensalo ◽  
Marianne Udd ◽  
Mia Rainio ◽  
Jorma Halttunen ◽  
Matias Sipilä ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
University Hospital ◽  
Long Term Results ◽  
Biliary Duct ◽  
Complication Rates ◽  
Biliary Sphincterotomy ◽  
Significant Difference ◽  
Upper Abdominal

Abstract Background Transpancreatic biliary sphincterotomy (TPBS) is an advanced cannulation method for accessing common bile duct (CBD) in endoscopic retrograde cholangiopancreatography (ERCP). If CBD cannulation is difficult, an endoscopist can open the septum between the pancreatic and biliary duct with a sphincterotome to gain access. Long-term results of this procedure are unclear. We wanted to evaluate the short- and long-term complications of TPBS on patients with native papilla and benign indication for ERCP. Patients and Methods ERCPs performed in Helsinki University Hospital between 2007 and 2013 were reviewed. The study group comprised 143 consecutive patients with TPBS and 140 controls (CG). Data were collected from patient records and a phone survey was performed as a follow-up ≥ 4 years after the index ERCP. Results Post-ERCP pancreatitis (PEP) developed in seven patients (4.9%) in TPBS and one patient (0.7%) in CG (p = 0.067). The rates of other acute complications were similar between the groups. ERCP ended with no access to CBD in four cases (2.8%) in TPBS. The median length of follow-up was 6 years in TPBS and 7 years in CG. During this period, three patients (2.1%) in TPBS and six patients (4.3%) in CG suffered from acute pancreatitis (AP) (p = 0.238). One (0.7%) patient in CG and none in TPBS developed chronic pancreatitis (CP). Abdominal pain was suffered by ten patients (6.9%) in TPBS and twelve patients (8.6%) in CG daily, whereas by six patients (4.2%) in TPBS and twelve patients (8.6%) in CG weekly. Conclusion TPBS is a useful procedure, with acceptable complication rates. No significant difference occurred between the groups when evaluating the short-term or long-term complications with a follow-up period of four to 10 years. Additionally, no significant differences occurred in upper abdominal pain, episodes of AP, or development of CP.

scholarly journals Asymmetric dental arch treatment with Forsus fatigue appliances: Long-term results

2019 ◽  
Vol 89 (5) ◽  
pp. 688-696 ◽  
Author(s):  
Mehmet Akın ◽  
Emire Aybuke Erdur ◽  
Onur Öztürk
Keyword(s):  
Repeated Measures ◽  
Class Ii ◽  
Long Term Results ◽  
Dental Arch ◽  
Retention Period ◽  
Repeated Measures Analysis ◽  
Dental Models ◽  
Digital Dental Models

ABSTRACT Objectives: To investigate the treatment efficacy and follow-up stability of the asymmetric Forsus appliance by evaluating longitudinal changes in dental arch asymmetry on digital dental models from 21 patients. Materials and Methods: Maxillary and mandibular reference lines were used for measurements of intra-arch asymmetry at pretreatment (T1), posttreatment (T2), and 4.2 years after treatment (T3). Maxillary and mandibular measurements were performed relative to the dental midline and anterior reference line on digital dental models. To determine the amount of asymmetry between the Class I and Class II sides of a given arch, all maxillary and mandibular parameters were measured on each side of the model separately. Repeated-measures analysis of variance/paired sample t-tests were performed to evaluate dental arch asymmetries at the P &lt; .05 level. Results: The alveolar transverse dimensions of the posterior segment of both arches were increased during treatment (P &lt; .05) and remained stable during the retention period. Class II subdivision malocclusion was caused by distal positioning of the mandibular canine, premolars, and first molar on the Class II side (P &lt; .05). Asymmetry was resolved by treatment with asymmetric Forsus appliances. The resolved asymmetry remained stable over the long term. There were no significant differences between T2 and T3 (P &gt; .05). Conclusions: The asymmetric Forsus appliance can be used to treat dental arch asymmetry in patients with Class II subdivision malocclusions.

scholarly journals Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1124-1124
Author(s):  
Jiang Ji ◽  
Ziqi Wan ◽  
Jing Ruan ◽  
Yali Du ◽  
Miao Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Aplastic Anemia ◽  
Median Time ◽  
Relapse Rate ◽  
Real World ◽  
Reticulocyte Count ◽  
Efficacy And Safety ◽  
Overall Response ◽  
Significant Difference

Abstract Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P&gt;0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

scholarly journals A Combined Prospective and Retrospective Comparison of Long-Term Functional Outcomes Suggests Delayed Loss of Ambulation and Pulmonary Decline with Long-Term Eteplirsen Treatment

2021 ◽  
pp. 1-14 ◽  
Author(s):  
Olga Mitelman ◽  
Hoda Z. Abdel-Hamid ◽  
Barry J. Byrne ◽  
Anne M. Connolly ◽  
Peter Heydemann ◽  
...  
Keyword(s):  
Natural History ◽  
Repeated Measures ◽  
Proportional Hazards ◽  
Clinical Care ◽  
Standard Of Care ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Background: Studies 4658-201/202 (201/202) evaluated treatment effects of eteplirsen over 4 years in patients with Duchenne muscular dystrophy and confirmed exon-51 amenable genetic mutations. Chart review Study 4658-405 (405) further followed these patients while receiving eteplirsen during usual clinical care. Objective: To compare long-term clinical outcomes of eteplirsen-treated patients from Studies 201/202/405 with those of external controls. Methods: Median total follow-up time was approximately 6 years of eteplirsen treatment. Outcomes included loss of ambulation (LOA) and percent-predicted forced vital capacity (FVC%p). Time to LOA was compared between eteplirsen-treated patients and standard of care (SOC) external controls and was measured from eteplirsen initiation in 201/202 or, in the SOC group, from the first study visit. Comparisons were conducted using univariate Kaplan-Meier analyses and log-rank tests, and multivariate Cox proportional hazards models with regression adjustment for baseline characteristics. Annual change in FVC%p was compared between eteplirsen-treated patients and natural history study patients using linear mixed models with repeated measures. Results: Data were included from all 12 patients in Studies 201/202 and the 10 patients with available data from 405. Median age at LOA was 15.16 years. Eteplirsen-treated patients experienced a statistically significant longer median time to LOA by 2.09 years (5.09 vs. 3.00 years, p < 0.01) and significantly attenuated rates of pulmonary decline vs. natural history patients (FVC%p change: –3.3 vs. –6.0 percentage points annually, p < 0.0001). Conclusions: Study 405 highlights the functional benefits of eteplirsen on ambulatory and pulmonary function outcomes up to 7 years of follow-up in comparison to external controls.

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