The safety of brodalumab for the treatment of psoriasis

ABSTRACT

Introduction: Brodalumab is a newly developed targeted biologic agent for the treatment of psoriasis that blocks IL-17 receptor A.

Areas covered: This review sought to provide a detailed overview on safety of brodalumab for the treatment of psoriasis. A PubMed search was conducted for relevant literature. Here we review the efficacy and safety data from key phase II, phase III and open-label extension clinical trials, as well as systematic reviews and meta-analyses.

Expert opinion: The unique mechanism of action of brodalumab offers advantages on efficacy over other targeted treatments, with a quick onset of action and long-term maintenance of treatment response. Brodalumab has a favorable safety profile, similar to other IL-17 inhibitors. Infections, especially mucocutaneous candidiasis, must be monitored. Suicidal ideation was detected in brodalumab trials, although a causal relationship has not been revealed. Brodalumab is a highly efficacious and comparably safe therapeutic choice in patients with moderate to severe psoriasis, especially when rapid control of the disease is desired.     

Safety of secukinumab in the treatment of psoriasis

ABSTRACT

Introduction: Secukinumab is a human monoclonal antibody that selectively targets and neutralizes interleukin (IL)-17A, a cytokine that is normally involved in mucocutaneous defense against extracellular organisms and is abnormally expressed in psoriasis. In 2015, secukinumab was the first IL-17A inhibitor approved for the treatment of moderate-to-severe psoriasis.

Areas covered: This review evaluates the safety profile of secukinumab for the treatment of moderate-to-severe psoriasis and its role in the clinical landscape. A literature search was performed for articles published through February 2016; additional data from a pooled safety analysis of 10 Phase II and III secukinumab studies were reviewed.

Expert opinion: Collectively, these studies show that secukinumab demonstrates a highly favorable safety profile, especially compared with commonly used psoriasis treatments such as methotrexate and TNF-α blockers. More specifically, secukinumab carries no increased risks for end-organ toxicities, serious infection, multiple sclerosis, reactivation of latent tuberculosis or hepatitis B, leukemia/lymphoma, and nonmelanoma skin cancer. Mucocutaneous candidiasis is a common side effect and occurs at a rate of 3.55/100 subject-years with secukinumab 300 mg, yet these infections usually do not interfere with maintenance of secukinumab therapy. The combination of proven efficacy and safety make secukinumab an excellent new treatment choice for individuals with moderate-to-severe psoriasis.     

Emerging topical treatments for psoriasis

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease which classically presents as erythematous, scaly plaques affecting extensor surfaces of the limbs, scalp and trunk. Approximately 80% of patients have a mild-to-moderate form routinely treated with topical medications, whereas phototherapy, systemic and biological therapies are typically reserved for treatment of moderate-to-severe psoriasis.

Areas covered: The major advances in psoriasis therapy in the past 15 years have been in new immunomodulatory and biological molecules, with a significant unmet need to have new, efficient and safe topical treatment options for the large percentage of patients for whom systemic therapy is not indicated. The available topical therapies (corticosteroids and vitamin D3 analogs) have remained relatively unchanged over the past several decades. This article reviews emerging topical drugs and formulations currently under evaluation in clinical trials.

Expert opinion: The time is right for a revolution in our topical therapy armamentarium. It has lagged significantly behind the systemic biological evolution of new drug development. Our large psoriasis population with mild-to-moderate psoriasis certainly deserves potent but safe and innovative topical agents with a new mode of action as well as with long-lasting clinical efficacy.     

Safety of the current drug treatments for vitiligo

ABSTRACT

Introduction: Vitiligo is an acquired depigmenting skin disorder adversely affecting the patient’s quality of life. Despite the presence of several treatment modalities, ranging from medical to physical to surgical options, none is curative. Each modality has its own drawbacks and side effects. Thus, the treatment modality needs to be tailored for each individual patient taking into consideration the disease characteristics and also its efficacy and safety to obtain a favorable risk–benefit ratio.

Areas covered: This review highlights the different treatment modalities utilized in vitiligo up until 4 November 2019 along with their adverse effects and contraindications, if any.

Expert opinion: All the medications have their own adverse effects and contraindications. We have included the most commonly used topical corticosteroids, which may result in striae, cutaneous atrophy, and tachyphylaxis, to the recently introduced biologics, which may induce hypersensitivity reactions, systemic toxicities, and even malignancies. However, more long-term studies are needed to assess the safety of these medications, especially the newer ones, to provide a safe and effective treatment for this disorder.     

Safety considerations with combination therapies for psoriasis

ABSTRACT

Introduction: Psoriasis is a chronic inflammatory skin disease that waxes and wanes, and long-term remission can be difficult to achieve regardless of disease severity. Currently, numerous treatment options are available for psoriasis including steroid and non-steroid topical agents, phototherapy, oral systemic agents, and biologics, with many more therapeutic agents under development.

Areas covered: This article will review various combination therapy strategies such as rotational therapy and sequential therapy and describe a variety of safe and effective combination therapies for the treatment of psoriasis. Two or more agents with different mechanisms of action and safety profiles can be used to achieve and/or maintain adequate disease control while minimizing the toxicity of treatments. Combination therapy can also be used when a single agent is not enough for treating recalcitrant disease. Choosing a combination regimen that maximizes safety and efficacy while considering patient usability and compliance can be a challenge.

Expert opinion: Given the various treatment options currently available for psoriasis and more agents under development, combination therapy will continue to be a valuable treatment strategy for any patient with psoriasis. It is crucial for clinicians to carefully consider the fine balance between safety and efficacy when combining various therapeutic agents.     

Biologics in the treatment of pustular psoriasis

ABSTRACT

Introduction

Pustular psoriasis is a group of skin diseases characterized by neutrophil infiltration in the epidermis and formation of sterile pustules. Conventional treatments, such as retinoids and immunosuppressive drugs, have improved the clinical manifestations; however, many patients suffer from drug-related toxicity or are resistant to therapy.     

Emerging oral drugs for psoriasis

Introduction: Psoriasis is a chronic, immune-mediated inflammatory disease that classically presents with well-demarcated, scaly, erythematous plaques on the extensor surfaces of the extremities, scalp, and trunk. Nails and joints are frequently affected as well. Whereas a significant number of patients maintain adequate control with topical therapy, up to 25% of patients will require phototherapy, oral systemic medication, or biologic therapy.

Areas covered: The majority of recent advances in therapeutic options for moderate-to-severe psoriasis have been in biologic therapies whereas development of new oral agents has lagged behind. Currently, oral agents are largely confined to methotrexate, acitretin, cyclosporine and most recently apremilast. This article reviews emerging oral treatments for moderate-to-severe psoriasis.

Expert opinion: Despite the recent FDA approval of apremilast, the development of new oral treatments for moderate-to-severe psoriasis has not kept pace with biologic therapies. There continues to be a need for safe and effective long-term oral therapies.     

Long-term safety of ustekinumab for psoriasis

Introduction: The biologic, Ustekinumab (Stelara®, Centocor, Inc., Malvern, PA, USA), is a fully human monoclonal antibody with a high affinity for the shared p40 subunit of interleukins 12 and 23 (IL-12 and IL-23). Approved for use in treating moderate-to-severe psoriasis in 2009, there has been considerable interest in the long-term safety of ustekinumab.

Areas covered: This review discusses the use of ustekinumab in the treatment of psoriasis and its potential to be an effective and well-tolerated therapy. A literature search was performed for articles published through April 2013 to identify any safety concerns.

Expert opinion: Our results indicate that ustekinumab has demonstrated higher efficacy rates as compared to traditional therapies; and with a favorable dosing schedule and stable safety profile, patients with recalcitrant disease will now have another option for treatment.     

Guselkumab for the treatment of moderate-to-severe plaque psoriasis

Introduction: Guselkumab is a human monoclonal antibody targeting the p19 subunit of IL-23 that has been approved for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This medication blocks the IL-23/IL-17 axis, which has been implicated in playing a key role in the pathogenesis of psoriasis.

Areas covered: This review outlines the pharmacologic properties, safety, and efficacy of guselkumab for the treatment of plaque psoriasis.

Expert commentary: Guselkumab is the first IL-23 specific inhibitor to be approved for the treatment of plaque psoriasis. Phase II and III clinical trial results have demonstrated excellent safety and efficacy of guselkumab. IL-23 inhibitors may offer potential benefits over existing therapies for moderate-to-severe plaque psoriasis in terms of safety, frequency of administration, and efficacy. Long-term safety data will be critical in evaluating the role of guselkumab in the treatment of psoriasis.     

Safety update of etanercept treatment for moderate to severe plaque psoriasis

ABSTRACT

Introduction: Conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) for patients with psoriasis are often linked to inadequate outcomes and risk of multiple adverse effects. Biologic agents such as etanercept (ETN) have revolutionized the therapeutic management of psoriasis, allowing the treatment of most difficult cases, and fragile patients.

Areas covered: The authors searched PubMed using the term ‘psoriasis,’ ‘etanercept,’ and ‘safety.’ Articles considered by the authors to be most relevant, such as randomized controlled studies, cohort studies, and review articles placing emphasis on studies of efficacy and safety were selected. Case reports and letters relating to safety were also included. The main sources of data referenced by these articles were also included in the review. Besides, to get the relevant studies, the reference lists were examined to identify the potentially available studies. The aim of this review is to describe the safety profile of ETN, used for psoriasis treatment, focusing on related clinical implications.

Expert opinion: ETN has a favorable safety profile, and its use should be largely considered in psoriatic patients. Caution should be recommended in case of chronic heart failure, autoimmune disease, previous malignancies, familial history of demyelinating diseases, latent TBC infection, chronic HBV and HCV infection or HIV.     

利伐沙班用于超高龄非瓣膜性房颤患者的安全性评价

目的:观察超高龄非瓣膜性房颤(non-valvular fibrillation,NVAF)患者临床特点和抗凝治疗安全性。方法:回顾性分析武汉市第三医院2020年5月至2021年4月接受利伐沙班抗凝治疗的NVAF患者,根据年龄分为观察组(年龄≥80岁)和对照组(<80岁)。观察2组患者发生缺血性脑卒中、心肌梗死、全身性栓塞、大出血及死亡事件的风险。结果:116人完成随访,观察组59人,对照组57人。所有患者至少合并1种慢性疾病,低体质量和肾功能不全是超高龄NVAF患者的生理特点。93.2%患者服用低于标准剂量的利伐沙班,52.5%患者有高或中等依从性。随访结束,2组患者缺血事件、大出血、临床相关非大出血和死亡事件的发生率相似。结论:对于超高龄NVAF患者应充分评估卒中风险和出血风险,低于标准剂量利伐沙班能否达到预期效果需进一步研究。     

注射用益气复脉(冻干)在高龄患者应用中的安全性

目的 探讨注射用益气复脉（冻干）在高龄患者应用中的安全性。方法 回顾性分析天津医科大学总医院2017年7月—2017年12月,106例80岁及80岁以上应用注射用益气复脉（冻干）治疗的高龄患者的临床资料。结果 106例高龄患者应用注射用益气复脉（冻干）治疗,治疗前、后药物对患者肝肾功能均无不良影响,且其余不良反应轻微。结论 高龄患者应用注射用益气复脉（冻干）具有很好的安全性,且患者耐受性良好。     

Safety evaluation of apremilast for the treatment of psoriasis

Introduction: Psoriasis (PSo) is a chronic inflammatory skin disease associated with co-morbidities such as hypertension, diabetes, dyslipidemia and metabolic syndrome. It is a typothypical Th1/Th17 disease that affects from 2 to 3% of the world population. Numerous are the drugs that can be used in our clinical practice; the choice of these drugs depends on the characteristics of the patient.

Areas covered: Apremilast is the first oral small molecules to receive FDA approval for the treatment of adults with active psoriasis and psoriatic arthritis. It is a small-molecule that specifically inhibits the activity of cyclic AMP phosphodiesterase-4 (PDE4). Several analyses have been performed on data from phase III studies to assess apremilast safety and efficacy on psoriasis and psoriatic arthritis (PsA). Apremilast could also represent a treatment opportunity for those patients unresponsive to both systemic and biological agents or whose treatment was contraindicated.

Expert opinion: For its safety profile and easy route of administration, apremilast may offer an oral treatment option for those patients that discontinue treatments because of ineffectiveness, intolerability or ineligibility to the currently available drugs.     

The safety of treatment options for elderly people with acute myeloid leukemia

ABSTRACT

Introduction: Life expectancy in elderly patients with acute myeloid leukemia (AML) is a function of age, disability, and co-morbidity, combined with leukemia characteristics. There is currently no consensus regarding the optimal therapeutic strategy for older adults with AML. Although selected older adults with AML can benefit from intensive therapies, recent evidence supports the use of lower-intensity therapies in most patients and emphasizes the importance of tolerability and quality of life.

Areas covered: Results of the current clinical trials and safety data are reviewed.

Expert opinion: Treatment recommendations for elderly patients with AML need to be individualized. In order to avoid toxicities, hematologists should collaborate more with geriatricians to identify clues of vulnerability in elderly patients through the study of functional physical, physiological, cognitive, social, and psychological parameters.     

A drug safety evaluation of risankizumab for psoriasis

ABSTRACT

Introduction: Risankizumab is a fully human monoclonal antibody that selectively targets interleukin (IL)-23A, interfering with the IL-23/17 axis that plays a crucial role in keratinocyte proliferation. In 2019, risankizumab was approved globally for the treatment of moderate-to-severe psoriasis.

Areas covered: The safety profile of risankizumab for the treatment of psoriasis is assessed in this review. A literature search was performed on 18 October 2019, and additional data from pooled safety analyses were evaluated.

Expert opinion: Drugs blocking the IL-23 pathway are the most recently approved treatment for psoriasis, and risankizumab seems to be the most effective one among the three IL-23 blockers approved. Risankizumab was generally well tolerated in the clinical trials and was found to be relatively safe. The safety profile of risankizumab is generally similar in clinical trials compared to adalimumab and ustekinumab. In a subset of patients with latent tuberculosis, no active tuberculosis developed after risankizumab treatment for 55 weeks without tuberculosis prophylaxis. The combination of safety, efficacy and less frequent injection (every 12 weeks) make risankizumab an attractive new choice for individuals with moderate-to-severe psoriasis. However, the long-term impact of anti-drug antibodies (24%) observed in pivotal studies as well as safety concerns in those with viral infections, hepatitis, malignancies and those in endemic tuberculosis areas, await further studies.     

The potential utility of tildrakizumab: an interleukin-23 inhibitor for the treatment of psoriasis

Introduction: The approved biologic therapies are effective for the treatment of psoriasis, but have limitations. Tildrakizumab has a different mechanism of action and is a humanized immunoglobulin G1κ that binds to the p19 subunit of IL23.

Areas covered: Phase I, II and III clinical trials investigated the pharmacokinetics, efficacy, safety and immunogenicity of tildrakizumab for patients with psoriasis. The mean half-life of tildrakizumab is between 20.2 to 28.2 days. Tildrakizumab achieved a PASI 75 of 66% and 74% at week 16 for the doses of 100 mg and 200 mg respectively in a phase IIb randomised clinical trial (RCT), and PASI 75 of 61%/64% and 62%/66% at week 12 for 100 mg and 200 mg respectively in two phase III RCTs. Frequently associated adverse events include headache and upper respiratory tract infection.

Expert opinion: By recent standards tildrakizumab has relatively modest efficacy, possibly due to a less intensive dosing regimen. Head-to-head RCTs in comparison with current therapies such as ustekinumab and secukinumab respectively are needed to understand its relative efficacy. In addition, trials in patients who have failed multiple biologics and patients with psoriatic arthritis would be helpful. The low frequency of injections in the tildrakizumab maintenance regimen may encourage adherence and aid persistence.     

An update on the safety of apremilast for the treatment of plaque psoriasis

ABSTRACT

Introduction: Apremilast is an oral phosphodiesterase inhibitor, approved for moderate to severe psoriasis in adults. Despite the advancement in dermatology, and the introduction of newer biological drugs, apremilast this is the only novel oral medication that has been introduced to treat psoriasis in the past two decades. Like additional other more traditional oral medications, its advantages and disadvantages should be discussed and compared within this group of oral-systemic medications.

Area covered: We conducted a review to assess the safety, efficacy, and adherence of apremilast for psoriasis treatment. The aim of this paper was to provide an overview of apremilast regarding its mechanism of action, indications, and adverse events.

Expert opinion: Apremilast has been found to be a safe and efficacious drug for moderate-to-severe psoriasis, and despite minor numerous side effects, most of the patients adhere to the therapy. Therefore, overall, it may be easily embraced as the drug of choice for this category. However, for more severe psoriasis cases newer biological drugs seem to be superior to apremilast.     

Advances in treating psoriasis in the elderly with small molecule inhibitors

Introduction: Due to the chronic nature of psoriasis, the population of elderly psoriasis patients is increasing. However, many elderly psoriatic patients are not adequately treated because management is challenging as a result of comorbidities, polypharmacy, and progressive impairment of organ systems. Physicians may hesitate to use systemic or biologic agents in elderly psoriasis patients because of an increased risk of adverse events in this patient population. Small molecule medications are emerging as promising options for elderly patients with psoriasis and other inflammatory conditions.

Areas covered: Here we review the efficacy, safety and tolerability of small molecule inhibitors apremilast, tofacitinib, ruxolitinib, baricitinib, and peficitinib in the treatment of psoriasis, with focus on their use in the elderly population.

Expert opinion: Although small molecule inhibitors demonstrate efficacy in elderly patients with psoriasis, they will require larger head-to-head studies and post-marketing registries to evaluate their effectiveness and safety in specific patient populations. Apremilast, ruxolitinib, and peficitinib are effective agents with favorable side effect profiles; however, physicians should exercise caution when prescribing tofacitinib or baricitinib in elderly populations due to adverse events. The high cost of these drugs in the U.S. is likely to limit their use.