Update on Clinical Trials of Tadalafil Demonstrates No Increased Risk of Cardiovascular Adverse Events

Abstract Introduction Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). Methods We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42–65 years) using individual-level participant data. Participants with a FI >0.24 were considered “frail”. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex and disease severity. In negative binomial regression we modelled serious adverse event rates on FI, and combined results for each index condition in a random-effects meta-analysis. Results All trials included frail participants: prevalence 7–21% in T2DM trials, 33–73% in RA trials, and 15–22% in COPD trials. Increased disease severity and female sex were associated with higher FI in all trials. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21–1.75), 1.45 (1.13–1.87) and 1.99 (1.43–2.76) for T2DM, RA and COPD, respectively. Conclusion Frailty is identifiable and prevalent among middle aged and older participants in phase 3/4 drug trials and has clinically important safety implications. Trial data may be harnessed to better understand chronic disease management in people living with frailty.

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Evaluating longitudinal toxicity of cetuximab in patients with metastatic colorectal cancer (mCRC): A pooled analysis from 1,302 patients in the ARCAD database.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3610 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3610-3610

Author(s):

Guilherme Lopes ◽

Jane Yeojeong So ◽

Katrin Marie Sjoquist ◽

Curtis L. Olswold ◽

Eric Van Cutsem ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Onset Time ◽

Pooled Analysis ◽

Lower Grade ◽

Site Location ◽

Increased Risk ◽

Ecog Ps ◽

Reporting Method ◽

Entire Treatment

3610 Background: Chronic lower grade adverse events (AE) can negatively affect a patient’s quality of life but it is difficult to capture using a traditional toxicity reporting approach. A novel AE reporting method was recently developed to describe, summarize, and present longitudinal AE profiles(Lopes et al, 2021). We leveraged this method to describe and compare the AE profiles of doublet chemotherapy (DC) + Cetuximab and DC alone in mCRC patients. Methods: This AE reporting method utilizes two additional AE metrics to complement the maximum (max) toxicity grade usually reported in clinical trials. Onset time indicates the time period in which max grade for an AE occurred for the first time, defined here as “early” (i.e. within first 42 days) and “late” (i.e. after the 42nd day). AE Load (AEL) indicates the overall severity of an AE in the entire treatment. AEL varies from 0 to 1. Higher AEL indicates a worse overall severity of that AE over time. AEL is the key metric for describing chronic AE. We included patients receiving DC + cetuximab (n = 738) and DC alone (n = 564 [ref group]) from two randomized first-line trials in the ARCAD database. Diarrhea, rash, hand-foot syndrome (HFS), fatigue, anorexia, and mucositis were examined and adjusted for backbone (FOLFOX vs. FOLFIRI), ECOG PS, sex, site location, dose reduction, and treatment length. Results: For rash, DC + cetuximab had a higher risk of G3+ (21% vs. 0.5%; odds ratio {OR} [95% confidence interval {CI}] = 50 [16,157], p < 0.001), increased overall severity over the entire treatment (AEL = 0.257 vs. 0.069; Adjusted difference in means–Mdiff [95% CI] = 0.22 [0.21,0.23], p < 0.001), and increased risk of early onset (67% vs. 33%; OR [95% CI] = 4.3 [2.7,6.7], p < 0.001). DC + cetuximab also had higher AEL for rash across max grades (p < 0.001 within G1, G2, and G3+). For HFS, DC + cetuximab had a higher risk of G3+ (OR [95% CI] = 6.0 [2.5,14], p < 0.001), increased overall severity (AEL = 0.139 vs. 0.087; Mdiff [95% CI] = 0.03 [0.03,0.04], p < 0.001), and slightly earlier onset (12.4 vs. 13.9 weeks; Mdiff, weeks [95% CI] = -4.9 [-0.80,-9.0], p = 0.021). Within each max grade, DC + cetuximab did not have higher AEL of HFS. No associations were found for diarrhea, fatigue, anorexia, or mucositis. Conclusions: The addition of cetuximab is associated with higher grade, more persistent, and more immediate rash. The higher severity in HFS with the addition of cetuximab appears to be related to higher grade but not chronic HFS. This method may be useful to describe different strategies, e.g. intermittent cetuximab. It provided a comprehensive view of acute and chronic toxicity profiles supporting its potential interest as new metrics in clinical trials. Lopes GS, Tournigand C, Olswold CL, et al. Adverse event load, onset, and maximum grade: A novel method of reporting adverse events in cancer clinical trials. Clinical Trials. 2021;18(1):51-60

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Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution

Endocrine Related Cancer ◽

10.1530/erc-13-0499 ◽

2014 ◽

Vol 21 (2) ◽

pp. 371-381 ◽

Cited By ~ 234

Author(s):

Mabel Ryder ◽

Margaret Callahan ◽

Michael A Postow ◽

Jedd Wolchok ◽

James A Fagin

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Immune Checkpoint ◽

Cytotoxic T Lymphocyte ◽

Hormone Replacement ◽

Symptomatic Relief ◽

Hormone Secretion ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Increased Risk

Novel immune checkpoint blockade with ipilimumab, an antibody blocking the cytotoxic T-lymphocyte antigen 4 (CTLA4), is revolutionizing cancer therapy. However, ipilimumab induces symptomatic, sometimes severe, endocrine immune-related adverse events (irAEs) that are inconsistently recognized and reported. The objective of this review was to comprehensively characterize the incidence, presentation, and management of endocrinopathies following ipilimumab therapy in a single center that is highly specialized in immune checkpoint blockade. We carried out a retrospective analysis of endocrine irAEs in melanoma patients receiving ipilimumab therapy in clinical trials between 2007 and 2013. A total of 256 patients were included in this analysis. We reviewed pituitary-, thyroid-, and adrenal-related hormone test results, as well as radiographic studies and the clinical histories of patients, to identify and characterize cases of hypophysitis, hypothyroidism, thyroiditis, and adrenal dysfunction. Following ipilimumab therapy, the overall incidence of hypophysitis was 8% and that of hypothyroidism/thyroiditis 6%. Primary adrenal dysfunction was rare. Therapy with a combination of ipilimumab and nivolumab, an anti-programmed cell death 1 (PDCD1, also called PD1) receptor antibody, was associated with a 22% incidence of either thyroiditis or hypothyroidism and a 9% incidence of hypophysitis. Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion rarely recovered. In summary, we observed that CTLA4 blockade alone, and in particular in combination with PD1 blockade, is associated with an increased risk of symptomatic, sometimes severe, hypophysitis as well as thyroid dysfunction. Prompt initiation with hormone replacement reverses symptoms. Evaluation and reporting of endocrine irAEs in clinical trials should be done using standardized diagnostic criteria and terminology.

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Identifying frailty in trials: an analysis of individual participant data from trials of novel pharmacological interventions

BMC Medicine ◽

10.1186/s12916-020-01752-1 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Peter Hanlon ◽

Elaine Butterly ◽

Jim Lewsey ◽

Stefan Siebert ◽

Frances S. Mair ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Disease Severity ◽

Negative Binomial ◽

Frailty Index ◽

Chronic Obstructive ◽

Pharmacological Interventions ◽

Phase 3 ◽

Serious Adverse Events ◽

Increased Risk

Abstract Background Frailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD). Methods We constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42–65 years) using individual-level participant data. Participants with a FI > 0.24 were considered ‘frail’. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex, and disease severity. In negative binomial regression, we modelled serious adverse event rates on FI and combined results for each index condition in a random-effects meta-analysis. Results All trials included frail participants: prevalence 7–21% in T2DM trials, 33–73% in RA trials, and 15–22% in COPD trials. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21–1.75), 1.45 (1.13–1.87), and 1.99 (1.43–2.76) for T2DM, RA, and COPD, respectively. Conclusion The upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.

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Update on Adverse Effects of HIV Integrase Inhibitors

Current Treatment Options in Infectious Diseases ◽

10.1007/s40506-019-00203-7 ◽

2019 ◽

Vol 11 (4) ◽

pp. 372-387

Author(s):

Agnieszka Kolakowska ◽

Anaenza Freire Maresca ◽

Intira Jeannie Collins ◽

Johann Cailhol

Keyword(s):

Clinical Trials ◽

Weight Gain ◽

Adverse Effects ◽

Adverse Events ◽

Real Life ◽

Future Research ◽

People Living With Hiv ◽

Childbearing Age ◽

Vascular Events ◽

Increased Risk

Abstract Purpose of review The goal of this paper is to provide an up-to-date review of adverse events related to the class of integrase strand transfer inhibitors (INSTIs), which became the class of choice in few years. We sought answers specifically to issues pertaining to neuropsychiatric adverse events, as well as weight gain, which were the two most important categories of adverse events raised in recent studies based on real-life experience. The primary focus of this paper is on adults with a brief summary on pregnant women and children/adolescents. Recent findings Dolutegravir (DTG) bears the heaviest burden of neuropsychiatric side effects. Weight gain was reported with all INSTIs, although there are methodological caveats in the analyses and the findings need to be interpreted with caution. Moreover, due to recent findings on neural tube defects in infants exposed to dolutegravir during their peri-conception period, its use is not recommended for women of childbearing age without proper birth control method, while raltegravir remains the only drug which may be prescribed without caution. Given the importance of cognitive and metabolic co-morbidities in people living with HIV in regard to their quality of life, future research needs to focus on long-term effects of INSTIs in relation to these adverse events. Pharmacogenetics seems to be a promising tool. Safety during pregnancy is also another important issue to further clarify. Summary INSTIs are a generally well-tolerated class of antiretrovirals (ARV), and has a higher antiviral potency compared to other classes of ARV. Clinicians and patients need however to be aware of some red flags when starting with and monitoring patients on INSTIs. All INSTIs can lead to mild increases in creatinine levels, usually without clinical significance, but caution is needed in patients with low eGFR (<30ml/min), when using other nephrotoxic drugs, such as as tenofovir disoproxil. Neuro-psychiatric (NP) effects are to be monitored with INSTIs, especially with DTG (though reports are at times contradictory); clinicians might want to avoid DTG for patients with history of severe NP symptoms, until clarity is provided. Weight gain was reported with all INSTIs, especially with DTG, with possible differential effects according to sex and ethnicity (female and non-white patients being at increased risk). This is worrying since patients from African descent are at higher risk of cardio-vascular events and increased body mass index (BMI) can cause further increase metabolic risk. There is possibly an additional effect of tenofovir alafenamide (TAF) on weight increase. Discrepancies between clinical trials – with low rates of adverse events – and reports from real-life settings might be due partly to under-representation of some groups of patients in clinical trials, and/or the short duration of follow-up, since some adverse effects may only occur after prolonged exposure. Preliminary data on safety of bictegravir (BIC), from clinical trials and non-trial settings, are very reassuring and seem to show lower rates of adverse events compared to DTG. Elvitegravir/cobicistat (EVG/cobi) need to be used with caution in patients with other co-morbidities given potential for polypharmacy, as it is the case for aging patients, because of the high potential of drug-drug interactions due to effects of the cobicistat booster. We are awaiting the release of cabotegravir (CAB), which could represent a good option for patients struggling with adherence, despite injection site reactions. Pharmacogenetics is a promising way to explore adverse effects occurrence in the INSTI class.

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Sex differences in adverse event reporting in SWOG chemotherapy, biologic/immunotherapy, and targeted agent cancer clinical trials.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11588 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11588-11588 ◽

Cited By ~ 1

Author(s):

Joseph M. Unger ◽

Riha Vaidya ◽

Kathy S. Albain ◽

Michael Leo LeBlanc ◽

Lori M. Minasian ◽

...

Keyword(s):

Clinical Trials ◽

Sex Differences ◽

Adverse Events ◽

Targeted Therapies ◽

Patient Reported Outcome ◽

Adverse Event Reporting ◽

Multiple Treatment ◽

Increased Risk ◽

Patient Reported ◽

Grade 3

11588 Background: Women have more adverse events (AEs) from chemotherapy than men, but few studies have explored sex differences in biologic/immunotherapies (BIs) or targeted therapies. We examined subjective (symptomatic) and objective AEs by sex across different treatments. Methods: We analyzed drug-related severe (grade 3) or worse AEs by sex in SWOG phase II and III clinical trials conducted between 1980-2018, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events (CTCAE). Subjective or symptomatic toxicities were defined as those aligned with the NCI’s new Patient-Reported Outcome (PRO) CTCAE; lab-based or physician-determined AEs were designated as objective. Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 19 objective AE categories were examined. Results: In total, 36,397 patients (women, 13,907 [38.2%]; men, 22,490 [61.8%]) experiencing 522,835 AEs on 297 trials with 385 treatment arms were analyzed. Overall, 29.1% (n = 10.860) had severe or worse toxicity. Women experienced an increased risk of severe symptomatic AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.31, 95% CI: 1.24-1.39, p < .0001), and targeted therapies (OR = 1.23, 95% CI: 1.06-1.43, p = .008). Women also had an increased risk of severe objective AEs for BIs (OR = 1.53, 95% CI: 1.32-1.78, p < .0001), chemotherapy (OR = 1.35, 95% CI: 1.28-1.43, p < .0001), but not targeted therapies (OR = 1.08, 95% CI: 0.94-1.25, p = .28). Across all treatments, sex differences were greater for hematologic (OR = 1.29, 95% CI: 1.24-1.35, p < .0001) v. non-hematologic (OR = 1.13, 95% CI: 1.08-1.18, p < .0001) objective AEs. Conclusions: The greater severity of both symptomatic and objective – especially hematologic – AEs in women across multiple treatment paradigms indicates broad-based sex-differences exist. This could be due to AE reporting, pharmacogenomics of drug metabolism and disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving BIs, suggesting studying AEs from these agents is a priority.

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Benefits and Risks of Chloroquine and Hydroxychloroquine in The Treatment of Viral Diseases: A Meta-Analysis of Placebo Randomized Controlled Trials

10.1101/2020.04.13.20064295 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jing Wang ◽

Li Yu ◽

Kefeng Li

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Viral Diseases ◽

Controlled Trials ◽

Significant Heterogeneity ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Increased Risk

AbstractBackground and ObjectiveRecently, in the scramble to find drugs to treat COVID-19, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have rapidly gained the public’s attention. In this study, we conducted a meta-analysis of randomized clinical trials (RCTs) to evaluate the efficacy and safety of CQ and HCQ in the treatment of viral diseases.MethodsWe searched PubMed, EMBASE, Cochrane Central, Web of Science, Clinical Trials Registries, CNKI, Wanfang Data, CQVIP, and Preprint Servers through April 4, 2020, for randomized controlled trials (RCTs) that examined the efficacy and safety of CQ and HCQ against viral infection. We analyzed pooled data on the overall efficacy, the relative risks over the placebo, and the prevalence of adverse events. Trial sequential analysis (TSA) was also performed to evaluate the random errors in the meta-analysis. Potential moderators of drug-placebo efficacy differences were analyzed by meta-regression.ResultsThe analysis included 11 RCTs with 2613 adult patients. Both the plasma viral load (standard mean difference: 0.29, 95% CI: −1.19 - 1.76, P = 0.70) and the improvement of clinical symptoms (odds ratio: 2.36, 95% CI: 0.81 - 6.92, P = 0.11) were not different between the intervention and placebo arm. There was significant heterogeneity for the efficacy assessment, which was primarily explained by the mean patients’ age and the sample size. Compared to the placebo, CQ and HCQ had increased risk of mild adverse events (risk ratio: 1.51, 95% CI: 1.35 - 1.70, P < 0.05, TSA adjusted 95% CI: 1.31 - 2.19), which were statistically significant in nervous, integumentary, and gastrointestinal systems. The most common adverse events were observed in the nervous system, with the pooled prevalence of 31.4 % (95% CI: 10.5% - 56.7%).ConclusionsInsufficient data were available to support the antiviral efficacy of CQ and HCQ due to the high heterogeneity caused by patients’ age. Mild side effects are expected for the current antiviral dose regimens of CQ and HCQ. Treatment outcomes may be enhanced by better-selected patients based on age and well-controlled adverse events.This meta-analysis was registered on OSF (ID: https://osf.io/386aw)

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Tolerability of dual checkpoint blockade with nivolumab and ipilimumab: A meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15149 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15149-e15149

Author(s):

Alejandro Ramon Carvajal ◽

Judy Huang ◽

Shenhong Wu

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Cancer Patients ◽

Fixed Effects ◽

Risk Mitigation ◽

Meta Analysis ◽

Checkpoint Blockade ◽

Discontinuation Rate ◽

Fixed Effects Model ◽

Increased Risk

e15149 Background: The dual checkpoint blockade of PD-1 and CTLA-4 with nivolumab and ipilimumab have been used extensively for cancer immunotherapy in clinical practice and trials due to its efficacy. A critical concern is the tolerability of the combination due to the increased risk of severe immune-mediated adverse events. A meta-analysis of clinical trials was performed to assess the treatment tolerability measured as discontinuation due to adverse events. Methods: A search through PubMed as well as abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until December 2019 was performed to identify clinical trials in which the combination of nivolumab and ipilimumab was given to cancer patients. Eligible clinical trials reported a discontinuation rate due to adverse events for the groups of patients receiving nivolumab and ipilimumab. A random or fixed effects model was used to determine summary incidences, relative risks, and 95% confidence intervals. Results: Seven clinical studies which included a total of 3,213 patients (combo: 1746, control: 1467) with various cancers were selected. Overall, the intolerability of nivolumab and ipilimumab measured as the summary incidence of discontinuation due to adverse events was 25.1% (95% CI: 17.8-34.1%). The rate varied significantly with the type of cancer (P < 0.001). The lowest discontinuation rate was in uveal melanoma, with a rate of 11% (95% CI: 2.9-34.2%), and the highest discontinuation rate was in melanoma at 46.3% (95% CI: 36.6-56.4%). In comparison with chemotherapy controls from randomized controls, the intolerability was significantly higher with an relative risk of 2.1 (95% CI: 1.78-2.84) for the combination. Conclusions: There is a substantial risk for intolerability in cancer patients receiving the combination nivolumab and ipilimumab. Further studies are needed for risk mitigation.

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MO326CORTICOSTEROIDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF REPORTED ADVERSE EVENTS IN RANDOMISED CONTROLLED TRIALS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0084 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Rupert Major ◽

Robert Grant ◽

Keith Nockels ◽

Mrinal Das ◽

Jürgen Floege ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Autoimmune Disease ◽

Adverse Events ◽

Autoimmune Diseases ◽

Iga Nephropathy ◽

Meta Analysis ◽

Controlled Trials ◽

Systemic Corticosteroids ◽

Increased Risk

Abstract Background and Aims Systemic corticosteroids are commonly used to treat autoimmune diseases such as immunoglobulin A (IgA) nephropathy. Corticosteroids are associated with increased risk of adverse events such as weight gain, hyperglycaemia, hypertension, infection and bone fracture occur frequently and affect safe long-term use. Adverse events of corticosteroids in clinical trials may have been historically under-reported. We aimed to perform a systematic review and meta-analysis of reported adverse events of corticosteroids in autoimmune diseases, with a particular focus on kidney pathologies. Method Pre-registered protocol systematic review (Prospero ID: CRD42020206650). The following databases were searched from 1980 to 2020: Placebo-controlled trials in adults with any form of autoimmune disease receiving intravenous or oral corticosteroids were included in the systematic review. Trial protocol major adverse events and all-cause mortality were included as the current study’s main outcome. Results After exclusion of duplicates between databases, 4490 OVID MEDLINE and 4987 Cochrane abstracts were reviewed. In total, 110 published clinical trials were identified for inclusion in the study: 14 clinical trials were in kidney autoimmune diseases, including 8 in IgA nephropathy. Results of their published adverse events, including where appropriate meta-analysis, will be presented. Specific results of those studies of kidney pathologies such as IgA nephropathy will be presented. Conclusion This systematic review with a pre-registered protocol identified 110 clinical trials examining systemic corticosteroid use versus placebo in autoimmune diseases. These results will help to understand whether the risks of systemic corticosteroids for autoimmune disease has been historically under-reported in the medical literature and whether a clear risk and benefit profile of corticosteroids in autoimmune disease can be assessed.

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Safety of Efalizumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: Review of Clinical Data. Part II

Journal of Cutaneous Medicine and Surgery ◽

10.1177/120347540500900607 ◽

2005 ◽

Vol 9 (6) ◽

pp. 313-323 ◽

Cited By ~ 2

Author(s):

Kim A. Papp ◽

Charles Camisa ◽

Stephen P. Stone ◽

Ivor Caro ◽

Xiaolin Wang ◽

...

Keyword(s):

Clinical Trials ◽

Adverse Events ◽

Safety Profile ◽

Controlled Trials ◽

Efficacy And Safety ◽

Chronic Plaque Psoriasis ◽

Serious Adverse Events ◽

The Third ◽

Increased Risk ◽

Favorable Safety

Background: The efficacy and safety of efalizumab have been evaluated in multiple clinical trials. ObjectiveThe purpose of this review is to provide an overview of the safety profile of efalizumab during the clinical trials. Methods: Twelve-week data from four placebo-controlled trials were pooled and analyzed. Data from patients receiving 13—60 weeks of efalizumab therapy were pooled to evaluate longer-term safety. Results: The most common adverse events were mild to moderate, self-limiting, flulike symptoms that were most frequent following the first two efalizumab doses; by the third dose the incidence was comparable to placebo. Serious adverse events were observed in 2.2% and 1.7% of efalizumab- and placebo-treated patients, respectively. Nonserious adverse events leading to withdrawal were infrequent and similar to placebo (2.8% vs 1.8%). There does not appear to be increased risk of end-organ toxicity, infection, or malignancy in efalizumab-treated patients. Conclusion: Efalizumab was well tolerated, with a favorable safety profile.

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