Abstract 1122‐000087: Long‐Term Outcomes of Anterior Communicating Artery Aneurysm Treated with Coiling: Subset Analysis of SMART Registry

Introduction : The purpose of this study was to assess the long‐term clinical outcomes of anterior communicating artery (ACoA) aneurysm treated with coiling. Methods : Data on patients with an ACoA aneurysm were extracted from a prospective multicenter registry (SMART) that enrolled patients with intracranial aneurysms or other neurovascular abnormalities who underwent coiling. The primary effectiveness outcome was retreatment through follow‐up, and the primary safety outcome was procedural device‐related serious adverse events within 24 hours. Results : Of the 995 adults enrolled in the SMART registry, 230 had an ACoA aneurysm (Table). The average patient age was 59.1 years (SD 12.5), and 62.6% were female. A modified Rankin Scale score of 0 to 2 was present in 89.6% of patients. Most aneurysms were small (93.9%) and saccular (87.8%). The aneurysm was wide necked in 57.7% of patients and was ruptured in 35.7%. Coiling was stent assisted in 39.1% of patients and balloon assisted in 14.8%. Retreatment through follow‐up occurred in 8.1% (15/185) of patients—6.8% (12/176) of patients with a small aneurysm, 33.3% (3/9) of patients with a large aneurysm, 4.0% (5/126) of patients with an unruptured aneurysm, 16.9% (10/59) of patients with a ruptured aneurysm, 9.9% (9/91) of patients with unassisted coiling, 5.6% (4/71) of patients with stent‐assisted coiling, and 7.4% (2/27) of patients with balloon‐assisted coiling. Procedural device‐related serious adverse events within 24 hours occurred in 5.2% of patients—5.1% (11/216) of patients with a small aneurysm, 7.1% (1/14) of patients with a large aneurysm, 6.1% (9/148) of patients with an unruptured aneurysm, 3.7% (3/82) of patients with a ruptured aneurysm, 3.6% (4/111) of patients with unassisted coiling, 5.6% (5/90) of patients with stent‐assisted coiling, and 11.8% (4/34) of patients with balloon‐assisted coiling. No deaths occurred within 24 hours of the procedure. At 1 year, 91.8% (167/182) of patients had a Raymond–Roy Occlusion Classification of Class I or II. From immediately after the procedure to 1 year, progressive occlusion was observed in 29.1% (53/182) of patients, and stable occlusion was observed in 56.6% (103/182) of patients. At 1 year, the all‐cause mortality rate was 4.3%, and at a 1‐year follow‐up, a modified Rankin Scale score of 0 to 2 was present in 86.2% (112/130) of patients. Conclusions : Coiling of ACoA aneurysm was safe and had durable 1‐year results.

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Imatinib Long Term Effects (ILTE) Study: An Independent, International Study in CML Patients.

Blood ◽

10.1182/blood.v112.11.1099.1099 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1099-1099

Author(s):

Carlo Gambacorti-Passerini ◽

Dong-Wook Kim ◽

François-Xavier Mahon ◽

Giuseppe Saglio ◽

Fabrizio Pane ◽

...

Keyword(s):

Adverse Events ◽

International Study ◽

Imatinib Treatment ◽

Long Term Effects ◽

First Line ◽

Eligibility Criteria ◽

Serious Adverse Events ◽

Second Cancers

Abstract Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on industry-sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an industryindependent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA). ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in Complete Cytogenetic Response (CCyR) after two years of imatinib treatment. Study endpoints were survival, serious adverse events (SAE, including second cancers), toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, loss of CCyR, and development of PCR negativity. A total of 957 patients were enrolled, 92% of which met eligibility criteria. The median age of eligible patients was 50 (range 15–92) years; 59% of patients were males and the median follow-up was 3.1 years (excluding the first 2 years of treatment). As of Dec. 31 2007, 2564 person years were available for analysis. Eleven deaths were observed (only 3 of them caused by relapsed CML), with a standardized rate of 0.4/100 person years and an observed/expected ratio of 0.48 (95% CI = 0.24–0.85). One-hundred SAE were recorded (rate 3.9/100 person years, most frequent type “heart failure”), with 21% being considered related to imatinib. Second cancers were documented in 28 patients (rate 1.1/100 person years), with an observed/expected ratio of 1.27 (95% CI = 0.84–1.84). Among the 576 NSAE recorded (0.65/patient) the most frequent types were “edema, cramps, skin fragility, diarrhea”; 71% of them were related to imatinib. A total of 12 patients (1.4 %) discontinued imatinib because of toxicities during the period of observation. Thirty-four patients lost CCyR, corresponding to a rate of 1.4/100 person years (1.0 in patients with imatinib as first-line treatment, 1.5 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 214 patients (24.5%) developed durable (> 1 year) PCR negativity. In conclusion, the first report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates lower than expected in an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately ¼ of cases. Follow-up and further analysis are ongoing. (Presented on behalf of the ILTE Investigators group)

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Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register

Annals of the Rheumatic Diseases ◽

10.1136/ard.2007.087411 ◽

2008 ◽

Vol 68 (5) ◽

pp. 635-641 ◽

Cited By ~ 139

Author(s):

F H M Prince ◽

M Twilt ◽

R ten Cate ◽

M A J van Rossum ◽

W Armbrust ◽

...

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Adverse Events ◽

Rheumatoid Factor ◽

Serious Adverse Events ◽

American College Of Rheumatology ◽

Systemic Jia ◽

Long Term Follow Up ◽

Remission Criteria

Objective:We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes.Methods:At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded.Results:We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3–7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year).Conclusions:Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).

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Long-term Results of Enterprise Stent-Assisted Coiling of Cerebral Aneurysms

Neurosurgery ◽

10.1227/neu.0b013e3182571953 ◽

2012 ◽

Vol 71 (2) ◽

pp. 239-244 ◽

Cited By ~ 111

Author(s):

Kyle M. Fargen ◽

Brian L. Hoh ◽

Babu G. Welch ◽

G. Lee Pride ◽

Giuseppe Lanzino ◽

...

Keyword(s):

Scale Score ◽

Cerebral Aneurysms ◽

High Volume ◽

Vascular Reconstruction ◽

Long Term Results ◽

Modified Rankin Scale ◽

Volume Data ◽

Stent System

Abstract BACKGROUND: The Enterprise Vascular Reconstruction Device and Delivery System (Cordis; the Enterprise stent) was approved for use in conjunction with coiling of wide-necked aneurysms in 2007. No published long-term aneurysm occlusion or complication data exist for the Enterprise system. OBJECTIVE: We compiled data on consecutive patients treated with Enterprise stent-assisted coiling of aneurysms from 9 high-volume neurointerventional centers. METHODS: A 9 center registry was created to evaluate large volume data on the delayed safety and efficacy of the Enterprise stent system. Pooled data were compiled for consecutive patients undergoing Enterprise stent-assisted coiling at each institution prior to May 2009. RESULTS: Two-hundred twenty-nine patients with 229 aneurysms, 32 of which were ruptured aneurysms, were included in the study. Mean clinical and angiographic follow-up was 619.6 ± 26.4 days and 655.7 ± 25.2 days, respectively. Mean aneurysm size was 9.2 ± 0.4 mm. Fifty-nine percent of patients demonstrated 100% coil obliteration and 81% had 90% or higher occlusion at last follow-up angiography. A total of 19 patients (8.3%) underwent retreatment of their aneurysms during the follow-up period. Angiographic in-stent stenosis was seen in 3.4% and thromboembolic events occurred in 4.4%. Overall, 90% of patients who underwent Enterprise-assisted coiling had a modified Rankin Scale score of 2 or less at last follow-up. A poor modified Rankin Scale score was strongly associated with rupture status (P < .001). CONCLUSION: Although this study is limited by its retrospective nature, the Enterprise stent system appears to be an effective, safe, and durable treatment for intracranial aneurysms when used in conjunction with coiling.

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Imatinib Long Term Effects (ILTE) Study: An International Study to Evaluate Long-Term Effects in CML Patients.

Blood ◽

10.1182/blood.v114.22.2199.2199 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2199-2199

Author(s):

Dong-Wook Kim ◽

Laura Antolini ◽

François-Xavier Mahon ◽

Francois Guilhot ◽

Michael Deininger ◽

...

Keyword(s):

Adverse Events ◽

Conflicts Of Interest ◽

International Study ◽

Imatinib Treatment ◽

Long Term Effects ◽

First Line ◽

Serious Adverse Events ◽

Second Cancers

Abstract Abstract 2199 Poster Board II-176 Imatinib is an effective first line therapy for chronic myeloid leukemia (CML) and has substantially changed its biological and clinical behavior. Durable complete cytogenetic responses (CCyR) were reported in the majority of patients, with a rather benign side effect profile, despite the ‘off target’ inhibition of several other kinases, including Kit, PDGFR and Lck. Since available information is largely based on sponsored trials and long-term field studies are lacking, the ILTE study was conceived as an independent, academic, multicenter trial supported by the Italian Drug Safety Agency (AIFA) and Regione Lombardia. ILTE is an international study on a retrospective cohort and includes 31 centers in Europe, North/South America, Africa, Middle East and Asia; therefore it is uniquely positioned to present a global picture of imatinib long-term effects. Consecutive patients with Ph+ CML who started imatinib between 01 September 1999 and 31 December 2004 were eligible if they were in CCyR after two years of imatinib treatment. Study endpoints were (a) survival, (b), serious adverse events (SAE, including second cancers), (c) toxicities not qualifying as SAE (NSAE) but judged by the referring physician as substantially impacting quality of life, (d) loss of CCyR, and (e) development of PCR negativity. A total of 948 patients were enrolled, 88% of which met eligibility criteria after centers were visited and monitored. The median age of eligible patients was 51 (range 18-92) years; 59% of patients were males and the median follow-up was 4.0 years (excluding the first 2 years of treatment). As of Dec. 31 2008, 3255 person years were available for analysis. Twenty one deaths were observed (only 6 of them [28%] caused by relapsed CML), with a standardized rate of 0.6/100 person years and an observed/expected ratio of 0.7 (95% CI = 0.43-1.07, p=ns). A total of 138 SAE were recorded (rate 4.2/100 person years, most frequent type “heart failure”), with 19.5% being considered related to imatinib. Second cancers were documented in 29 patients (rate 0.9/100 person years), with an observed/expected ratio of 1.02. Among the 761 NSAE recorded (rate 23.4/100 person years) the most frequent types were cramps, asthenia,edema, skin fragility, diarrhea; 69% of them were considered related to imatinib. A total of 18 patients (2.2 %) discontinued imatinib because of toxicities during the period of observation. Forty patients lost CCyR, corresponding to a rate of 1.3/100 person years (1.0 in patients with imatinib as first-line treatment, 1.4 in patients who were treated with imatinib >6 months after diagnosis), with stable or increasing rates over time. Finally, 256 patients (36.0 %) developed durable (> 1 year) PCR negativity. In conclusion, this report from ILTE shows that CML patients on imatinib die unfrequently of CML related causes, do not appear to have substantially higher second cancer rates than the general population, have mortality rates similar to an age/sex matched population and do not show new types of imatinib-related adverse events. They also experience a low but steady rate of loss of CCyR and develop PCR negativity in approximately 1/3 of cases. Follow-up and further analysis are ongoing. (Presented on behalf ofthe ILTE Investigators group) Disclosures: No relevant conflicts of interest to declare.

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Five-year follow-up of patients enrolled in the NEAT 001/ANRS 143 randomized clinical trial: NEAT 001/ANRS 143 LONG TERM study

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa056 ◽

2020 ◽

Vol 75 (6) ◽

pp. 1618-1622

Author(s):

François Raffi ◽

Aurélie Gaultier ◽

Anton Pozniak ◽

Jean-Michel Molina ◽

Heiko Jessen ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Randomized Clinical Trial ◽

Virological Failure ◽

Tenofovir Disoproxil Fumarate ◽

Integrase Inhibitor ◽

Serious Adverse Events ◽

Long Term Study

Abstract Background Few long-term data are available in subjects having initiated ART with an NRTI-sparing regimen. Objectives Outcomes of subjects enrolled in the NEAT 001/ANRS 143 randomized clinical trial (comparing ritonavir-boosted darunavir + raltegravir versus ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were retrospectively collected, through anonymized electronic case report forms, up to 6 years post-enrolment. Methods The last NEAT 001 visit (Week 96) was conducted in 745/805 randomized subjects (363/401 ritonavir-boosted darunavir + raltegravir and 382/404 ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine). Of these, 430 were enrolled in NEAT 001/ANRS 143 LONG TERM (NLT) study (201 raltegravir, 229 tenofovir disoproxil fumarate/emtricitabine), with a median follow-up of 44.4 months. Results During NLT follow-up, the proportion of AIDS, non-AIDS events, virological rebound and serious adverse events, discontinuation for virological failure and for adverse events did not differ between groups; discontinuations for virological failure since NEAT 001 inclusion were more frequent in subjects with baseline CD4 <200 cells/mm3 (11.9% versus 5.3%; P = 0.077). At last follow-up, a quarter of subjects (22.2% for ritonavir-boosted darunavir + raltegravir and 29.7% for ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine) were still receiving their initial regimen. Integrase inhibitor exposure was not associated with weight gain (P = 0.48), while tenofovir disoproxil fumarate exposure was associated with a trend to higher creatinine increase (P = 0.067). Conclusions After a median of 5.6 years, subjects initiating ritonavir-boosted darunavir + raltegravir or ritonavir-boosted darunavir + tenofovir disoproxil fumarate/emtricitabine experienced few serious clinical adverse events. Most discontinuations were for reasons unrelated to adverse events or virological failure.

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Safety and Potential Risks with Fecal Microbiota Transplantation

10.5772/intechopen.95907 ◽

2021 ◽

Author(s):

Pratyusha Gaonkar

Keyword(s):

Adverse Events ◽

Therapeutic Potential ◽

Fecal Microbiota Transplantation ◽

Standard Of Care ◽

Fecal Microbiota ◽

Serious Adverse Events ◽

Recurrent Clostridium Difficile Infection ◽

Long Term Follow Up

The therapeutic potential of Fecal Microbiota Transplantation (FMT) is greatly proved worldwide in the recent years. The use of FMT is now an accepted treatment modality and effective standard of care for some patients owing to its success in treating recurrent Clostridium Difficile Infection (rCDI). However, it is still evolving and longer term follow-up data regarding safety are required. Post-FMT serious adverse events (SAEs) have been varied between studies, however have included significant morbidity necessitating hospital admission and mortality in the follow-up period. The follow-up of FMT recipients should be long enough to completely establish efficacy/adverse events. Furthermore, it is recommended that FMT should be offered with caution to immunosuppressed patients, in whom FMT appears efficacious without significant additional adverse effects. In the wake of COVID-19 situation, stringent policies in screening the FMT donors have to be put forth to ensure patient safety. There is a need for high-quality, large, prospective, randomized controlled trials and long-term follow-up investigating screened donors and recipients to evaluate the long term safety and the risk–benefit profile of this promising therapy.

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Long-term treatment of endometriosis with dienogest: Real-world results from the VIPOS study

Journal of Endometriosis and Pelvic Pain Disorders ◽

10.1177/2284026521993688 ◽

2021 ◽

pp. 228402652199368

Author(s):

Sabine Moehner ◽

Kerstin Becker ◽

Jens A Lange ◽

Sophia von Stockum ◽

Marco Serrani ◽

...

Keyword(s):

Adverse Events ◽

Real World ◽

Health Care Professionals ◽

Study Entry ◽

Safety Signal ◽

Real World Data ◽

Serious Adverse Events ◽

Long Term Treatment

Introduction: The Visanne Post-approval Observational Study (VIPOS) was designed to assess the safety of dienogest 2 mg (DNG, Visanne) compared to other hormonal endometriosis treatments. Methods: Large, prospective, non-interventional, active surveillance study in six European countries (Germany, Poland, Russia, Hungary, Switzerland, and Ukraine). Women with a new hormonal therapy for endometriosis were enrolled by gynecologists and specialized centers between 2010 and 2016 and observed for up to 7 years. Self-administered questionnaires during study entry and follow-up collected information on baseline characteristics, health status and endometriosis treatment. Self-reported clinical outcomes of interest were validated by health care professionals. Results: Among the >27,000 enrolled participants, 3262 women started DNG use either at study entry or during follow-up. A total of 798 study participants used DNG during follow-up continuously for 15 months or longer (DNG long-term users). When comparing the occurrence of serious adverse events (SAE) in users treated with DNG, no safety signal emerged for long-term users; the SAE incidence rate per 10,000 women-years was 367.7 (95% CI: 274.1–481.9) in DNG long-term users and 416.4 (349.1–492.5) in short-term users (treated with DNG for less than 15 months). Conclusions: Previous data on DNG long-term safety were derived from studies with relatively low numbers of patients and limited follow-up time. VIPOS provided valuable real-world data on the long-term use of DNG 2 mg in around 800 women treated in Europe and observed no safety signal regarding serious adverse events.

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Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: A systematic review of non-randomized studies

10.1101/2021.05.27.21257921 ◽

2021 ◽

Author(s):

Dena Zeraatkar ◽

Matthew Cooper ◽

Arnav Agarwal ◽

Robin Vernooij ◽

Gareth Leung ◽

...

Keyword(s):

Systematic Review ◽

Chronic Pain ◽

Adverse Events ◽

Cochrane Central Register ◽

Medical Cannabis ◽

Management Options ◽

Serious Adverse Events ◽

Randomized Studies

Objective: To establish the risk and prevalence of long-term and serious harms of medical cannabis and cannabinoids for chronic pain. Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE, PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 1, 2020. Study selection: Non-randomized studies reporting on harms of medical cannabis or cannabinoids in people living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data, and assessed risk of bias. We used random-effects models for all meta-analyses and the GRADE approach to evaluate the certainty of evidence. Results: We identified 39 eligible studies that enrolled 12,143 patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2 to 41.2) among users of medical cannabis or cannabinoids for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6 to 30.6). However, very low certainty evidence indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are uncommon and typically occur in fewer than one in 20 patients. We compared studies with <24 weeks and ≥ 24 weeks cannabis use and found more adverse events reported among studies with longer follow-up (test of interaction p < 0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared to other pain management options, such as opioids. Conclusions: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events. Future research should compare long-term and serious harms of medical cannabis with other management options for chronic pain, including opioids.

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International Randomized Study of Interferon Vs STI571 (IRIS) 8-Year Follow up: Sustained Survival and Low Risk for Progression or Events in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Imatinib.

Blood ◽

10.1182/blood.v114.22.1126.1126 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1126-1126 ◽

Cited By ~ 242

Author(s):

Michael Deininger ◽

Stephen G O'Brien ◽

François Guilhot ◽

John M Goldman ◽

Andreas Hochhaus ◽

...

Keyword(s):

Adverse Events ◽

Research Funding ◽

Cytogenetic Response ◽

Term Therapy ◽

Cell Transplant ◽

Minimal Risk ◽

Serious Adverse Events ◽

Equity Ownership

Abstract Abstract 1126 Poster Board I-148 Background The IRIS study demonstrated superior safety and efficacy of imatinib (IM) relative to interferon-αa + cytarabine. Based on results from this trial, IM is currently recommended as front-line therapy for CML-CP patients (pts). We report 8-yr follow-up of IRIS, evaluating long-term efficacy and safety of IM. Methods The 553 pts randomized to first-line IM were evaluated for cytogenetic and molecular responses, event-free survival (EFS), progression to accelerated-phase (AP) or blast crisis (BC), overall survival (OS), discontinuations, and frequency of serious adverse events (SAEs). EFS was defined as time until the first occurrence of any of the following: death from any cause, progression to AP/BC, loss of a complete hematologic response or major cytogenetic response, or an increasing white cell count to > 20 × 109/L. Yearly progression rates were calculated using the life-table method considering available follow-up. Following study drug discontinuation, pts were followed for OS and stem cell transplant (SCT) information. Results At the 8-yr data cut-off, 304 (55%) pts remained on IM study treatment, and 45% had discontinued treatment due to adverse events (AEs)/safety (6%), unsatisfactory therapeutic outcome (16%), SCT (3%), death (3%) or other reasons (17% for withdrawal or lack of renewal of consent and miscellaneous). No new safety issues were identified in a long-term analysis of serious adverse events. Estimated EFS at 8 yr was 81% and freedom from progression to AP/BC was 92%. Estimated OS was 85% at 8 yr, and 93% when only CML-related deaths and those prior to SCT were considered. Three events occurred in yr 8: 1 progression to AP/BC and 2 deaths unrelated to CML (chronic obstructive pulmonary disease [1]; pneumonia aspiration [1]). The annual rates of progression to AP/BC in yr 4 to 8 after initiation of therapy were 0.9%, 0.5%, 0%, 0%, & 0.4%, respectively. Only 15 (3%) pts who achieved complete cytogenetic response (CCyR) progressed to AP/BC, all but 1 within 2 yr of achieving CCyR. BCR-ABL transcript numbers were monitored sequentially in 98 pts. Among these, the rate of major molecular response (MMR, < 0.1% BCR-ABL/control gene ratio on international scale) increased from 24% at 6 months (mo) and 39% at 12 mo to a best observed MMR rate of 86% with current follow-up. None of the pts with documented MMR at 12 mo progressed to AP/BC. To establish the relationship between early cytogenetic response (CyR) status and subsequent outcomes during 8 yr of IM treatment, we compared the cumulative incidence of achieving stable CCyR (defined as CCyR without subsequent event) vs the probability of an event (as described above but excluding CML-unrelated deaths) according to levels of CyR at 3, 6, 12, & 18 mo (Table 1). Pts with minor to partial CyR (> 0–65% Ph+ metaphases) at 3 mo and those with partial CyR (PCyR; > 0–35% Ph+ metaphases) at 6 & 12 mo were more likely to achieve a stable CCyR than have an event. Among pts with less than CCyR at 18 mo, the probability of an event was comparable to the probability of achieving stable CCyR. Conclusions CML-CP pts responding to IM had a low overall risk of progression to AP/BC. Most AP/BC events occurred early, with minimal risk after yr 3 and no evidence for an increase over time. Minor CyR at 3, PCyR at 6 and 12, and CCyR at 18 mo were associated with stable CCyR over the observation period. The safety profile of IM remains unchanged after 8 yr, with no previously unreported AEs identified over the past 36 mo. These data suggest that pts responding to IM are likely to maintain their responses on long-term therapy and confirm a favorable risk-benefit ratio in CML-CP pts. Disclosures Deininger: Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Calistoga: Research Funding; Genzyme: Research Funding. O'Brien:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Wyeth: Research Funding. Guilhot:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria. Goldman:Novartis: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau. Hochhaus:Novartis: Research Funding. Hughes:Bristol-Myers Squibb: Advisor, Honoraria, Research Funding; Novartis: Advisor, Honoraria, Research Funding. Radich:Novartis: Consultancy, Honoraria, Research Funding. Hatfield:Novartis: Employment, Equity Ownership, Patents & Royalties. Mone:Novartis: Employment. Filian:Novartis: Employment. Reynolds:Novartis: Employment. Gathmann:Novartis: Employment. Larson:Novartis: Consultancy, Honoraria, Research Funding. Druker:OHSU patent #843 - Mutate ABL Kinase Domains: Patents & Royalties; MolecularMD: Equity Ownership; Roche: Consultancy; Cylene Pharmaceuticals: Consultancy; Calistoga Pharmaceuticals: Consultancy; Avalon Pharmaceuticals: Consultancy; Ambit Biosciences: Consultancy; Millipore via Dana-Farber Cancer Institute: Patents & Royalties; Novartis, ARIAD, Bristol-Myers Squibb: Research Funding.

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P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.676 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S466-S467

Author(s):

S Fischer ◽

S Mesfin ◽

E Klenske ◽

H Schmitt ◽

F Vitali ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Cohort Study ◽

Adverse Events ◽

Disease Activity ◽

Bowel Disease ◽

Patient Visit ◽

Serious Adverse Events ◽

Inflammatory Bowel

Abstract Background SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients. Methods This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit. Results A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses). Conclusion Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.

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