Developing an instrument to assess patient preferences for benefits and risks of treating acute myeloid leukemia to promote patient-focused drug development

Objective Acute myeloid leukemia (AML) is a progressive blood cancer with few effective treatment options. As part of a patient-focused drug development (PFDD) initiative led by the Leukemia and Lymphoma Society (LLS), this study sought to use a community-centered approach to develop and pilot an instrument to measure patient preferences for the benefits and risks of treating AML.

Methods Instrument development was informed by a literature review, engagement with expert stakeholders (n?=?12), engagement with community stakeholders, and pre-testing. A discrete-choice experiment (DCE), in which participants made choices between 16 pairs of hypothetical treatments, was developed with five attributes: event-free survival, complete remission, time in hospital, short-term side-effects, and long-term side-effects. A pilot test was conducted and analyzed using conditional logistic regression. Results are presented using relative attribute importance (RAI) scores.

Results Patients with AML and caregivers were engaged in developing (n?=?15), pre-testing (n?=?13), and pilot testing (n?=?26) the instrument. The pilot included patients with AML (n?=?18) and caregivers of living or deceased patients with AML (n?=?8). Participants had a mean age of 50 years (range =24–81), and were mostly college educated (n?=?22), privately insured (n?=?21), and employed (n?=?13). Based on the DCE, complete remission was identified as the most important attribute (RAI =10), followed by event-free survival (3.7), time in hospital (2.8), long-term side-effects (2.3), and short-term side-effects (2.1).

Conclusion The mixed-methods approach to PFDD was welcomed by all stakeholders and there was strong endorsement to implement this DCE as part of a national survey.

• Key points for decision makers

• The Leukemia and Lymphoma Society (LLS) initiated an independent effort to promote patient-focused drug development (PFDD). This study presents the development and piloting of a preference study as a first step in this initiative.

• Results of this pilot study were used to guide a PFDD meeting to discuss the lived experience of patients and caregivers affected by AML.

• Productive engagement by all patients, caregivers, and stakeholders throughout the process resulted in strong endorsement of the project’s approach and recognition of the need to conduct a national study.

     

Emerging drugs for Guillain-Barré syndrome

Introduction: Intravenous immunoglobulin (IVIg) and plasma exchange are proven effective treatments for Guillain-Barré syndrome (GBS). However, this treatment is insufficient for many patients as 1 – 5% die, 25% need artificial respiration, 20% are still unable to walk unaided after 6 months and 85% have residual symptoms, such as fatigue and pain.

Areas covered: Strategies to design and conduct trials with new compounds and individualized regimens of IVIg are discussed. The development of specific immunomodulators is set against a background of recent insights in the pathophysiological mechanisms of GBS. Patients with poor prognosis can be identified in the early phase of disease using predictors such as high age, severe disability, preceding diarrhea and possibly low increase in serum IgG after standard IVIg treatment. An ongoing trial with a second IVIg dose in this group and the preclinical development of potential new treatments and their mode of action are discussed.

Expert opinion: GBS is a heterogeneous disease with considerable short- and long-term disability for which more effective and individualized treatments are required. Under investigation are new treatment strategies with adapted IVIg dosages based on prognostic factors and more specific immunomodulation, including complement inhibitors.     

Early remission status predicts long-term outcomes in patients with Crohn’s disease treated with certolizumab pegol

Background: In Crohn’s disease (CD), rapid response to anti–tumor necrosis factor therapy improves short- and medium-term outcomes, but the relationship between early remission (ER) and long-term remission is unclear.

Aims: This exploratory analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of certolizumab pegol predicted long-term remission.

Methods: Patients enrolled in PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies for moderate to severe CD, and received open-label certolizumab pegol 400?mg every 4 weeks for a total treatment duration of ≤7.5 years. Time to loss of remission between patients with and without ER (Harvey–Bradshaw Index ≤4 at or before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan–Meier estimates.

Results: At baseline, patients with (n?=?242) and without (n?=?148) ER had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8) years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with 45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein concentrations of 8.0 and 5.0?mg/L, respectively. Median certolizumab pegol plasma concentrations during the first 6 weeks of therapy were similar in both groups. Mean time to loss of remission was significantly longer in patients with versus without ER (2.77 vs. 1.14 years, p?<?0.0001).

Conclusions: In certolizumab pegol–treated patients with CD, ER appears to be an important predictor of long-term clinical remission. Prospective trials are needed to determine whether ER improves other long-term outcomes.     

A Systematic Review of the Symptom Profile and Course of Methamphetamine-Associated Psychosis

Objectives: The psychiatric symptom profile of methamphetamine-associated psychosis (MAP) has varied considerably across studies of different research designs. We performed a systematic review to examine the available evidence for specific psychotic symptoms associated with MAP, including the clinical course and longitudinal changes in this symptom profile. Methods: Five key electronic databases were searched to identify studies that examined the symptom profile or clinical course of MAP in individuals identified as having MAP. The reporting of specific psychiatric symptoms, and duration of symptoms where available, was recorded for each study. Results: Ninety-four articles were identified (n?=?7387), including case-control (k?=?29), cross-sectional (k?=?20), experimental (k?=?6), case report (k?=?29), and longitudinal (k?=?20) studies. Persecutory delusions, auditory and visual auditory hallucinations were by far the most commonly reported symptoms (reported in 65–84% of studies). Hostility, conceptual disorganization, and depression were reported in a large proportion of studies (31–53%). Negative symptoms were mostly absent (<20%). The median percentage of participants with persistent psychotic symptoms (>1?month duration) across studies was 25% (excluding case reports). Conclusion: Persecutory delusions, auditory and visual hallucinations, hostility, depression and conceptual disorganization are central to MAP, whereas negative psychotic symptoms are typically absent. An overrepresentation of institutionalized or male participants may have overemphasized negative symptoms and underreported affective symptoms in past research. Symptoms of MAP may persist beyond one month after drug cessation in some individuals. Clinicians are encouraged to manage affective symptoms in MAP individuals, and monitor for the development of chronic psychotic symptoms.     

Effects of non-medical switching on outcomes among patients prescribed tumor necrosis factor inhibitors

Objective: To evaluate health care use and outcomes among patients who experienced a non-medical switch of their prescribed anti-tumor-necrosis-factor biological agent (anti-TNF) for cost containment reasons.

Methods: Retrospective evaluation of Humedica electronic health records of patients ≥18 years old with anti-TNF treatment for immune conditions. Using natural language processing, stable patients who experienced a non-medical switch (for cost reasons) of their anti-TNF between 2007 and 2013 were identified (NMS cohort, n?=?158) and matched to patients who did not (control cohort, n?=?4804). Rates of office visits, emergency department visits, and hospitalizations at 30, 90, and 365 days following were evaluated. Medication-related adverse events, defined as subsequent medication change due to a side effect and/or efficacy-related reason were also compared.

Results: Adjusted rates of office visits were higher among the NMS cohort than the control cohort at 30 (46.4% vs. 31.7%, p?p?p?p?=?.003), 90 (31.6% vs 9.6%, p?p?p?=?.001).

Conclusion: Non-medical switching among patients prescribed anti-TNFs was associated with increased health care use, medication-related side effects, and reports of diminished efficacy.     

VITALITY: impact of adalimumab on health and disability outcomes in patients with Crohn’s disease,rheumatoid arthritis,or psoriasis treated in clinical practice in New Zealand

Objective: VITALITY, a 6-month, multicenter, prospective, observational study, assessed the effects of originator adalimumab (HUMIRA) on health and disability outcomes in patients with Crohn’s disease (CD), rheumatoid arthritis (RA), or psoriasis treated in routine clinical practice in New Zealand (NZ).

Methods: Biologic-naïve adults initiating adalimumab in accordance with NZ funding requirements were recruited. The primary endpoint was 6-month change from baseline in World Health Organization Disability Assessment Schedule (WHODAS) 2.0 score in all participants completing the study (full analysis set). Secondary endpoints included 6-month change in other patient-reported outcomes (PROs) of work activity and wellbeing (Work Productivity and Activity Impairment Questionnaire: General Health, Kessler Psychological Distress Scale, Flourishing Scale, and Subject Vitality Scale) and in disease-specific PRO measures.

Results: In total, 164 participants with severe disease initiating adalimumab completed the WHODAS 2.0 at baseline, of whom 114 (69.5%) completed the study at 6?months. Mean WHODAS 2.0 score halved from 15.2 points (SD =?±9.1) at baseline to 7.3 points (SD =?±7.2) after 6 months’ adalimumab treatment (mean difference = 7.9 points; 95% CI = 6.4–9.4; p?<?.001), with statistically significant improvements seen as early as 2?months after adalimumab initiation (p?<?.001). The proportion of participants with a WHODAS 2.0 score ≥ 10 more than halved, from 68.3% to 28.9%, between baseline and 6?months. Other PROs also improved significantly at 6?months, as did disease-specific measures. No new adalimumab safety signals were observed.

Conclusions: Health and disability outcomes improved significantly after 6?months of adalimumab use in NZ patients with severe CD, RA, or psoriasis.

Clinicaltrials.gov: NCT02451839.     

Identification of a subset of patients with acute myeloid leukemia characterized by long-term in vitro proliferation and altered cell cycle regulation of the leukemic cells

Objective: The malignant cell population of acute myeloid leukemia (AML) includes a small population of stem/progenitor cells with long-term in vitro proliferation. We wanted to compare long-term AML cell proliferation for unselected patients, investigate the influence of endothelial cells on AML cell proliferation and identify biological characteristics associated with clonogenic capacity.

Methods: Cells were cultured in medium supplemented with recombinant growth factors FMS-like tyrosine kinase-3 ligand, stem cell factor, IL-3, G-CSF and thrombopoietin. The colony-forming unit assay was used to estimate the number of progenitors in AML cell populations after 35 days of culture, and microarray was used to study global gene expression profiles between AML patients.

Results: Long-term cell proliferation was observed in 7 of 31 patients, whereas 3 additional patients showed long-term proliferation after endothelial cell coculture. Patient-specific differences in constitutive cytokine release were maintained during cell culture. Patients with long-term proliferation showed altered expression in six cell cycle-related genes (HMMR, BUB1, NUSAP1, AURKB, CCNF, DLGAP5), two genes involved in DNA replication (TOP2A, RFC3) and one gene with unknown function (LHFPL2).

Conclusion: We identified a subset of AML patients characterized by long-term in vitro cell proliferation and altered expression of cell cycle regulators that may be potential candidates for treatment of AML.     

The validation of a newly developed Arabic scale to assess patient-reported side-effects of antineoplastic agents

BackgroundMultiple scales in different languages were developed to measure patient-reported side effects of antineoplastics. However, these scales vary in their coverage of antineoplastics’ side effects, and none of them address both the severity and impact of antineoplastics’ side effects on patient quality of life. Hence, there is a need to develop a comprehensive, concise, and general scale to assess patients’ perceptions of both severity and impact of the commonly reported side effects of antineoplastics on patients’ activities of daily living and make it available in Arabic.ObjectivesTo develop and validate a new scale in Arabic to assess patient-reported antineoplastics’ side-effects among Arabic-speaking patients undergoing chemotherapy.MethodsA new scale was developed in Arabic that addresses 40 different emotional, cognitive, and physical side-effects of antineoplastics. The Antineoplastic Side effects Scale (ASES) contained three subscales focused on the side effects frequency, severity, and interference with patients’ activities of daily living. Seventy-eight patients with different cancer types were recruited from the oncology clinics of a university-affiliated tertiary care hospital in Riyadh, Saudi Arabia. The reliability of the questionnaire was examined using Cronbach’s alpha method. The construct validity was examined using principal component analysis with varimax rotation. The association between the scores of ASES subscales and various patient medical and sociodemographic characteristics were also examined.ResultsThe mean age of participants was 53.8 (12.5) years and most of them were female (65.3%) and married (84.6%). The ASES demonstrated good internal consistency (Cronbach’s alpha = 0.91). The severity of the perceived side effects and their impact on activities of daily living were positively associated with female gender.ConclusionThe newly developed ASES demonstrated good validity and reliability. This tool will hopefully help healthcare providers and patients to identify commonly reported antineoplastic side effects.     

Combination of aripiprazole with mood stabilizers for the treatment of bipolar disorder: from acute mania to long-term maintenance

Introduction: Bipolar disorder is characterized by a complex set of symptoms, including recurrent manic, depressive or mixed episodes. Acute and long-term treatment of patients with bipolar disorder is mandatory to prevent symptom relapse and episode recurrences. Outcomes with monotherapy are often unsatisfactory in clinical practice, hence combinations of mood stabilizers and antipsychotics are widely utilized in patients showing no or partial response to, as well as intolerance to, monotherapies. This may offer a therapeutic advantage, however, the possibility of an increased incidence of side effects should be considered.

Areas covered: This paper reviews the current treatment guidelines for the treatment of bipolar disorder and examines the rationale behind the use of aripiprazole in combination with mood stabilizers for acute and long-term treatment of bipolar disorder.

Expert opinion: The combination of aripiprazole and mood stabilizers seems to offer an effective and relatively well-tolerated option for the treatment of acute mania and for the maintenance treatment of patients with bipolar I disorder. The combination presents a lower risk of metabolic side effects compared with other combination therapies, but increases the risk of extrapyramidal side effects with long-term treatment. The aripiprazole–valproate combination seems to be particularly promising in the treatment of patients with comorbidities such as anxiety and drug abuse, obsessive-compulsive disorder and bipolar disorder, as well as in mixed depressive disorder. Controlled trials are necessary in order to confirm these observations and to provide a useful insight for improving the use of drug combinations in bipolar patients.     

A two-week,double-blind,placebo-controlled trial of Viola odorata,Echium amoenum and Physalis alkekengi mixture in symptomatic benign prostate hyperplasia (BPH) men

Context: As an alternative approach, administration of phytotherapeutic agents in management of benign prostate hyperplasia (BPH), is rapidly growing each day. Different authors have indicated effectiveness of Viola odorata L. (Violaceae), Echium amoenum Fisch. &; C.A.Mey. (Boraginaceae) and Physalis alkekengi L. (Solanaceae) in treatment of BPH. However, none have reported the beneficial outcomes of the mixture yet.

Objective: This study evaluates the therapeutical effects of V. odorata, E. amoenum and P. alkekengi mixture on symptomatic BPH patients.

Materials and methods: Eighty six symptomatic BPH patients with International Prostate Symptom Score (IPSS) of more than 13 and prostate volume of more than 30?cm³ were randomly allocated to receive a two-week course of placebo (control group) or 1?mL of mixed hydro-alcoholic solution of P. alkekengi, E. amoenum and V. odorata extracts (1.5, 1 and 1.5% respectively) (treatment group).

Results: IPSS score of incomplete urination (42.3?±?2.04%), frequency of urination (20.08?±?1.02%), intermittency (40.78?±?2.16%), urgency (60.91?±?3.14%), weak stream (50.58?±?2.14%), straining (55.67?±?2.53%) and nocturia (40.14?±?1.89%) in treatment group were significantly decreased after treatment compare to placebo receiving group. Furthermore, the prostate volume (16.92?±?0.89%) and extant urine volume (28.12?±?1.36%) also significantly decreased in treatment group compared to control group. No significant side effects or abnormalities in biochemical tests and urinalysis were observed throughout the study.

Discussion and conclusions: Based on results, mentioned mixture is safe and effective in improving life quality of patients suffering from BPH.     

Warfarin therapy in Chinese patients with atrial fibrillation treated with percutaneous coronary intervention: a 5 year follow-up retrospective cohort study

Objective: To evaluate warfarin use in Chinese patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) by investigating the stroke and major adverse cardiac and cerebral events (MACCEs) and bleeding events.

Methods: Retrospective cohort study of the 5?year follow-up of 1134 patients with AF who underwent PCI. The patients were grouped according to whether they received warfarin or not. Baseline characteristics and the occurrence of MACCEs and bleeding events were compared between the two groups using the CHA2DS2-VASc and HAS-BLED scoring. Cox regression analysis was used to identify factors related to the occurrence of MACCEs and bleeding.

Results: Overall MACCE (p?=?.008) and mortality (p?=?.004) rates were significantly lower in the warfarin group compared with the non-warfarin group. Major bleeding, minor bleeding and overall bleeding were comparable in the two groups. Recurrent myocardial infarction (HR?=?10.129, 95% CI?=?4.737–21.655; p?<?.001) and a baseline CHA2DS2-VASc score >4 (HR?=?2.035, 95% CI?=?1.121–3.692; p?=?.019) were independent predictors of MACCEs in the warfarin group. A baseline HAS-BLED score ≥3 (HR?=?5.498, 95% CI?=?3.773–8.013; p?<?.001) and previous bleeding (HR?=?3.058, 95% CI?=?1.319–7.088; p?=?.009) were independent predictors of bleeding.

Conclusions: Warfarin reduces the incidence of MACCEs but does not increase bleeding events in Chinese patients with AF who underwent PCI. For patients taking warfarin, recurrent myocardial infarction and a baseline CHA2DS2-VASc score >4 were related to MACCE occurrence.     

Quality of life of HIV-infected patients who switch antiretroviral medication due to side effects or other reasons

Objective: The objective of this study was to investigate changes in health-related quality of life (HRQOL) among HIV patients following switch from a first- to second-line antiretroviral therapy (ART) regimen.

Research design and methods: This was an observational study of adult HIV patients in the US at 35 academic and community health centers. Patients were required to be switching an antiretroviral regimen for the first time at the enrollment visit. Patients were assigned to a study cohort based on whether the switch was due to treatment-related side effects or for any other reason as reported by their physician. Patients completed the Medical Outcomes Study–Human Immunodeficiency Virus (MOS-HIV) health survey, the Depression, Anxiety, and Stress Scale Short Form (DASS-21), and the Human Immunodeficiency Virus Treatment Satisfaction Questionnaire–status (HIVTSQs) at the enrollment visit (baseline) and a follow-up survey was completed approximately 4 weeks later. The within cohort change in survey measures from baseline to follow-up was assessed by two-sample paired t-test.

Results: Patients who switched their ART regimen due to treatment-related side effects (n?=?50) had statistically significant improvements (p?<?.05, baseline to follow-up) in mean Physical and Mental Health Summary scores (MOS-HIV scale) and in all three HIVTSQ summary scores. Patients who switched for other reasons (n?=?44) did not experience statistically significant improvements in these same measures.

Conclusions: HIV patients whose regimen was switched due to treatment-related side effects experienced an improvement in QOL following the switch. Physicians should take the potential impact on QOL into consideration when deciding on a switch in ART regimen, particularly when patients are intolerant of their current treatment. The results are based on a patient survey and may have been influenced by recall and response bias.     

Glucocorticoid safety for treating rheumatoid arthritis

Introduction: Glucocorticoids (GCs) are often used in the treatment of rheumatoid arthritis and many other inflammatory diseases. Besides strong favorable effects on disease activity, GCs can cause (serious) side effects as well.

Areas covered: Side effects of GCs that are ranked as most important by rheumatologists as well as by patients are bone loss and fractures, cardiovascular events, hypertension, and diabetes mellitus. In evaluating these side effects, confounding by indication is a disturbing factor: not only the use of GCs can increase the risk of several side effects, but so can the activity of the underlying disease, which in turn is related to the amount of GCs that is prescribed to the patient.

Expert opinion: Generally, side effects predominantly occur in patients with a high disease activity and when used in high doses and for a long period of time. For these patients, caution and monitoring are most warranted. However, monitoring is not only recommended in patients with a high disease activity, and high-dose or long-term use of GCs, but in all GC users, since side effects may also occur in patients treated with low-dose GCs. When detecting possible negative effects in time, they might be managed and serious damage due to side effects might hopefully be prevented.     

Use of asenapine as add-on therapy in the treatment of bipolar disorder: a comprehensive review and case series

Introduction: Several randomized controlled trials (RCTs), conducted in schizophrenic and bipolar patients, have documented the efficacy and tolerability of asenapine as monotherapy both for short- and long-term treatment. However, evidence on its augmentative use is more limited and related to the manic/mixed phase of bipolar disorder (BD).

Areas covered: The present article reviews augmentative asenapine efficacy and safety/tolerability in the treatment of BD. It also includes some original cases of bipolar patients treated with add-on asenapine in the short- and long-term.

Expert opinion: To date, only a single RCT with manic/mixed patients with partial response to mood-stabilizer monotherapy supports the efficacy and safety/tolerability of augmentative asenapine to lithium/valproate, both in acute and long-term treatment. Additionally, two case reports confirm the overall effectiveness of augmentative asenapine to clozapine and valproate. Our case series, consisting of 4 bipolar patients treated with adjunctive asenapine to mood stabilizers and atypical antipsychotics – with treatment duration ranging from 1 to 14 months – provided clinical results that are consistent with literature data. Taken as a whole, available evidence seems to support the efficacy and safety of adjunctive asenapine in bipolar patients, though additional studies with active comparators are requested to confirm the current body of evidence.     

Efficacy and safety of 2% supramolecular salicylic acid compared with 5% benzoyl peroxide/0.1% adapalene in the acne treatment: a randomized,split-face,open-label,single-center study

Background: Topical drugs for mild to moderate acne include adapalene (ADA) and benzoyl peroxide(BPO). Supramolecular salicylic acid (SSA), a modified SA preparation, is considered as a new effective therapeutic scheme.

Objectives: To compare the safety and efficacy of 2% supramolecular SA (2% SSA) with 0.01% adapalene plus 5% benzoyl peroxide (5%BPO +0.1%ADA) for treatment of facial acne.

Materials and methods: This was an open-label, split face, randomized and single-centre clinical trial. Subjects with mild to moderate acne were enrolled. Two percent SSA cream were randomly applied on one side of the face while 5%BPO +0.1%ADA gel was applied on the opposite side for 28?days. The numbers of acne lesions, along with side effects of the targeted area were evaluated by the investigators at day 0, day 14, and day 28. Skin water content, TEWL and skin lightening indexes were measured at the same time.

Results: A total of 31 of acne patients completed the trial. Dates showed that 2% SSA had similar effects to 5%BPO +0.1%ADA in reducing papules/pustules (47.9% vs. 49.8%), non-inflammatory lesions (43.1% vs. 42.7%) and total lesions (44.1% vs. 45.6%; all p?>?0.05) at day 28. The skin barrier (skin hydration value and TEWL value), skin brightness (L* value) and erythema (a* values) indicators showed no statistical differences in the left and right sides of the face (p?>?0.05).

Conclusion: This study demonstrated that 2% SSA has a similar efficacy with 5%BPO +0.1%ADA in mild to moderate acne treatment. This might be a useful pilot study that could be used to support further larger clinical trials.     

康艾注射液联合盐酸埃克替尼片治疗晚期非小细胞肺癌的疗效观察

目的 探讨康艾注射液联合盐酸埃克替尼片治疗晚期非小细胞肺癌的临床疗效。方法 选取2013年5月-2018年5月在洛阳市第三人民医院就诊的82例晚期非小细胞肺癌患者,随机分为观察组（n=41）和对照组（n=41）。对照组给予患者口服盐酸埃克替尼片,3次/d,125 mg/次。观察组在对照组基础上给予康艾注射液40 mL,1次/d。两组均治疗1个月。对比两组治疗效果、生活质量和毒副作用发生率。结果 与对照组治疗总有效率12.20%和病情控制率48.78%比较,观察组治疗总有效率31.71%和病情控制率85.37%均显著升高（P<0.05）。两组呼吸困难、便秘、食欲缺乏发生率,角色功能、认知功能、社会功能评分及毒副作用（肝功能异常和腹泻）发生率比较,差异均无统计学意义。观察组疲倦、疼痛和皮疹发生率均显著低于对照组（P<0.05）;躯体功能、情绪功能评分均显著高于对照组（P<0.05）。结论 康艾注射液联合盐酸埃克替尼片治疗晚期非小细胞肺癌疗效显著,且安全性良好,值得临床推广。     

Pegylated-interferon-α2a in clinical practice: how to manage patients suffering from side effects

Introduction: The goal of antiviral therapy in patients with chronic hepatitis C is to slow or halt the progression of fibrosis and prevent the development of cirrhosis. Accordingly, antiviral treatment is proposed for a large population of patients with chronic hepatitis.

Areas covered: The standard-of-care for chronic hepatitis C is the combination of pegylated IFN (PEG-IFN) and ribavirin. The use of these drugs has been correlated with a range of adverse effects, including influenza-like symptoms, hematological changes and neuropsychiatric disturbances. The effects of these adverse events associated with PEG-IFN therapy are manifold and are a major reason why patients decline or stop therapy. This review addresses the screening for adverse event risk factors and guides the patient to success with adherence strategies.

Expert opinion: Knowledge of the side effects correlated with PEG-IFN is very relevant for clinicians because it can allow them to arrange the best methods for treating these effects and avoid the discontinuation of antiviral treatment. Moreover, the use of new antiviral drugs will considerably shorten treatment periods reducing many of the above-described side effects and, thus, increase adherence to scheduled therapy.