-
The British Journal of Dermatology Apr 2023
Topics: Humans; Methotrexate; Cyclosporine; Acitretin; Cohort Studies; Fumarates; Psoriasis
PubMed: 36763046
DOI: 10.1093/bjd/ljad030 -
Dermatologic Clinics Apr 2022Deciding when to start and selecting a specific systemic treatment for pediatric psoriasis patients can be a complex process involving many factors. Considerations... (Review)
Review
Deciding when to start and selecting a specific systemic treatment for pediatric psoriasis patients can be a complex process involving many factors. Considerations include type of psoriasis, severity, potential genetic etiologies, comorbidities, triggering events and characteristics unique to each patient. The constellation of clinical features and drug related factors may prompt selection of a specific agent. Systemic treatments may be considered on the basis of those that are "tried and true" (acitretin, methotrexate, cyclosporine, phototherapy) and "new and novel" (the biologic agents). Conventional systemic agents have decades of use to support their safety and efficacy and may be used in very flexible ways with titration of dose when maintenance is achieved or when flares occur. Targeted biologic therapies have overall reassuring safety profiles, can be very efficacious, and require little to no lab monitoring as compared to conventional systemics. However, they can be cost prohibitive and most are administered via injection. Here, we provide data and principles guiding the approach to therapy of moderate to severe psoriasis in children and use case examples to highlight several different clinical scenarios.
Topics: Child; Comorbidity; Drug Therapy, Combination; Humans; Methotrexate; Phototherapy; Psoriasis
PubMed: 35366969
DOI: 10.1016/j.det.2021.12.003 -
The Cochrane Database of Systematic... Jul 2020Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. This is an update of a Cochrane Review first published in 2012: we wanted to assess new trials, some of which investigated new interventions.
OBJECTIVES
To assess the effects of interventions for MF in all stages of the disease.
SEARCH METHODS
We updated our searches of the following databases to May 2019: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched 2 trials registries for additional references. For adverse event outcomes, we undertook separate searches in MEDLINE in April, July and November 2017.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of local or systemic interventions for MF in adults with any stage of the disease compared with either another local or systemic intervention or with placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcomes were improvement in health-related quality of life as defined by participants, and common adverse effects of the treatments. Key secondary outcomes were complete response (CR), defined as complete disappearance of all clinical evidence of disease, and objective response rate (ORR), defined as proportion of patients with a partial or complete response. We used GRADE to assess the certainty of evidence and considered comparisons of psoralen plus ultraviolet A (PUVA) light treatment as most important because this is first-line treatment for MF in most guidelines.
MAIN RESULTS
This review includes 20 RCTs (1369 participants) covering a wide range of interventions. The following were assessed as either treatments or comparators: imiquimod, peldesine, hypericin, mechlorethamine, nitrogen mustard and intralesional injections of interferon-α (IFN-α) (topical applications); PUVA, extracorporeal photopheresis (ECP: photochemotherapy), and visible light (light applications); acitretin, bexarotene, lenalidomide, methotrexate and vorinostat (oral agents); brentuximab vedotin; denileukin diftitox; mogamulizumab; chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine; a combination of chemotherapy with electron beam radiation; subcutaneous injection of IFN-α; and intramuscular injections of active transfer factor (parenteral systemics). Thirteen trials used an active comparator, five were placebo-controlled, and two compared an active operator to observation only. In 14 trials, participants had MF in clinical stages IA to IIB. All participants were treated in secondary and tertiary care settings, mainly in Europe, North America or Australia. Trials recruited both men and women, with more male participants overall. Trial duration varied from four weeks to 12 months, with one longer-term study lasting more than six years. We judged 16 trials as at high risk of bias in at least one domain, most commonly performance bias (blinding of participants and investigators), attrition bias and reporting bias. None of our key comparisons measured quality of life, and the two studies that did presented no usable data. Eighteen studies reported common adverse effects of the treatments. Adverse effects ranged from mild symptoms to lethal complications depending upon the treatment type. More aggressive treatments like systemic chemotherapy generally resulted in more severe adverse effects. In the included studies, CR rates ranged from 0% to 83% (median 31%), and ORR ranged from 0% to 88% (median 47%). Five trials assessed PUVA treatment, alone or combined, summarised below. There may be little to no difference between intralesional IFN-α and PUVA compared with PUVA alone for 24 to 52 weeks in CR (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.87 to 1.31; 2 trials; 122 participants; low-certainty evidence). Common adverse events and ORR were not measured. One small cross-over trial found once-monthly ECP for six months may be less effective than twice-weekly PUVA for three months, reporting CR in two of eight participants and ORR in six of eight participants after PUVA, compared with no CR or ORR after ECP (very low-certainty evidence). Some participants reported mild nausea after PUVA but no numerical data were given. One participant in the ECP group withdrew due to hypotension. However, we are unsure of the results due to very low-certainty evidence. One trial comparing bexarotene plus PUVA versus PUVA alone for up to 16 weeks reported one case of photosensitivity in the bexarotene plus PUVA group compared to none in the PUVA-alone group (87 participants; low-certainty evidence). There may be little to no difference between bexarotene plus PUVA and PUVA alone in CR (RR 1.41, 95% CI 0.71 to 2.80) and ORR (RR 0.94, 95% CI 0.61 to 1.44) (93 participants; low-certainty evidence). One trial comparing subcutaneous IFN-α injections combined with either acitretin or PUVA for up to 48 weeks or until CR indicated there may be little to no difference in the common IFN-α adverse effect of flu-like symptoms (RR 1.32, 95% CI 0.92 to 1.88; 82 participants). There may be lower CR with IFN-α and acitretin compared with IFN-α and PUVA (RR 0.54, 95% CI 0.35 to 0.84; 82 participants) (both outcomes: low-certainty evidence). This trial did not measure ORR. One trial comparing PUVA maintenance treatment to no maintenance treatment, in participants who had already had CR, did report common adverse effects. However, the distribution was not evaluable. CR and OR were not assessable. The range of treatment options meant that rare adverse effects consequently occurred in a variety of organs.
AUTHORS' CONCLUSIONS
There is a lack of high-certainty evidence to support decision making in the treatment of MF. Because of substantial heterogeneity in design, missing data, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be reliably established on the basis of the included RCTs. PUVA is commonly recommended as first-line treatment for MF, and we did not find evidence to challenge this recommendation. There was an absence of evidence to support the use of intralesional IFN-α or bexarotene in people receiving PUVA and an absence of evidence to support the use of acitretin or ECP for treating MF. Future trials should compare the safety and efficacy of treatments to PUVA, as the current standard of care, and should measure quality of life and common adverse effects.
Topics: Acitretin; Antineoplastic Agents; Bexarotene; Combined Modality Therapy; Humans; Immunologic Factors; Interferon-alpha; Mycosis Fungoides; Neoplasm Staging; PUVA Therapy; Photochemotherapy; Photopheresis; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32632956
DOI: 10.1002/14651858.CD008946.pub3 -
Expert Opinion on Drug Safety 2023A discussion of safety of systemic treatments for nail psoriasis is lacking, particularly in reference to approval of new therapies assessed for nail outcomes. A review... (Review)
Review
INTRODUCTION
A discussion of safety of systemic treatments for nail psoriasis is lacking, particularly in reference to approval of new therapies assessed for nail outcomes. A review of safety profiles for agents commonly utilized for treatment of nail psoriasis is warranted to help inform treatment choices. The PubMed database was searched on 5 April 20235 April 2023, with articles discussing safety of nail psoriasis systemic therapies identified and reviewed.
AREAS COVERED
Systemic treatments for nail psoriasis include biologic therapies (tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, interleukin-23 inhibitors, interleukin-12/23 inhibitors), small molecule inhibitors (apremilast, tofacitinib), and oral systemic immunomodulators (methotrexate, cyclosporine, acitretin), each with unique safety profiles and considerations. Herein, we discuss adverse events, contraindications, drug-drug interactions, screening/monitoring guidelines, as well as utilization for special populations, including pregnant, older, and pediatric patients.
EXPERT OPINION
The advent of targeted therapies, including biologic treatments and small molecule inhibitors, has revolutionized outcomes for nail psoriasis patients, but warrant review and monitoring for potential adverse events. Oral systemic immunomodulators have demonstrated moderate efficacy for nail psoriasis treatment, but are notable for frequent contraindications and drug-drug interactions. Further study of these agents and their use in special populations is needed to elucidate safety profiles for long-term use.
Topics: Humans; Child; Psoriasis; Methotrexate; Acitretin; Biological Therapy; Immunologic Factors
PubMed: 37329288
DOI: 10.1080/14740338.2023.2227560 -
American Journal of Clinical Dermatology May 2021Since the US Food and Drug Administration (FDA) approved tretinoin in 1971, retinoids alone or combined with other agents have become the mainstay of acne treatment.... (Review)
Review
Since the US Food and Drug Administration (FDA) approved tretinoin in 1971, retinoids alone or combined with other agents have become the mainstay of acne treatment. Retinoids act through binding to retinoic acid receptors, altering expression levels of hundreds of cellular proteins affecting multiple pathways involved in acne pathogenesis. Retinoids have evolved from first-generation agents, such as tretinoin, through chemical modifications resulting in a second generation (etretinate and acitretin for psoriasis), a third generation (adapalene and tazarotene) and, most recently, a fourth (trifarotene). For all topical retinoids, local irritation has been associated with poor tolerability and suboptimal adherence. Efforts to improve tolerability have utilized novel delivery systems and/or novel agents. This qualitative literature review summarizes the evolution of the four topical single-agent retinoids available for the treatment of acne in the US today and their various formulations, presenting the rationale behind their development and data from key studies.
Topics: Acne Vulgaris; Administration, Cutaneous; Cell Movement; Dermatologic Agents; Gene Expression Regulation; Humans; Leukocytes; Receptors, Retinoic Acid; Retinoids; Signal Transduction; Toll-Like Receptors; Treatment Outcome
PubMed: 33871811
DOI: 10.1007/s40257-021-00594-8 -
International Journal of Women's... Jul 2019The burden of psoriasis is particularly high for women, who report lower levels of happiness (women: 18.5%; men: 11.3% lower vs. general population) and are more likely... (Review)
Review
The burden of psoriasis is particularly high for women, who report lower levels of happiness (women: 18.5%; men: 11.3% lower vs. general population) and are more likely to experience stress (women: > 60%; men: 42%), loneliness (women: 25-28%; men: 19-24%), stigmatization (Feelings of Stigmatization Questionnaire score; women: 93.2; men: 78.0), and reduced sexual activity (women: 33%; men: 19%) compared with men. The onset of psoriasis is bimodal, with one incidence peak (15-30 years) that coincides with the prime reproductive age for women, which poses specific challenges for their treatment. However, well-established guidelines for the treatment of women of childbearing age are lacking. Many women experience stabilization (21%) or improvement (55%) of their skin during pregnancy, but up to a quarter can experience disease worsening, and postpartum flares are common (> 50%). Therefore, balancing the risk of treatment with the risk of uncontrolled disease is important. Because half of pregnancies are unplanned, the implications of therapeutic options must be considered for all women with psoriasis who are sexually active, irrespective of intentions to start a family. Timely initiation of these discussions by health care professionals is paramount to prevent unintentional toxicity to the developing fetus. For example, acitretin, methotrexate, and oral psoralen/ultraviolet A are all contraindicated in pregnancy. Reassuringly, safety data for other psoriasis treatments during pregnancy are increasingly available, particularly for anti-tumor necrosis factor therapies. Despite encouraging data from pregnancy exposure registries and clinical studies now being included in anti-tumor necrosis factor drug labels, comfort with prescribing these therapies to pregnant women remains low (U.S. dermatologists: 21%; EU-5 dermatologists: 10%). In this article, we review issues specific to treating women of childbearing age with psoriasis and highlight the need for treatment guidelines to ensure consistent care and optimal outcomes for these patients.
PubMed: 31360745
DOI: 10.1016/j.ijwd.2019.04.021 -
Drugs Apr 2020Erythrodermic psoriasis (EP) is an extreme and often refractory variant of psoriasis with high morbidity and increased mortality, and is frequently classified as a... (Review)
Review
Erythrodermic psoriasis (EP) is an extreme and often refractory variant of psoriasis with high morbidity and increased mortality, and is frequently classified as a dermatological emergency. The pathophysiology of EP is largely unknown but is thought to differ from that of plaque psoriasis. Treatment of EP is challenging, and usually based on clinical experience and patient co-morbidities, due to its low incidence and limited clinical evidence. Conventional treatments, such as topical glucocorticoid therapy, cyclosporin, acitretin, and methotrexate have some but limited efficacy in EP, and treatment discontinuation may result in flares. Newer biological drugs, including anti-TNF, anti-IL-17, and anti-IL-12/23 agents, have shown promise in therapeutic management of EP, but most of the available evidence is currently based on small case series and reports. Few studies have compared available treatment options for EP, and further clinical studies are necessary to provide clinical data and optimal treatment guidelines for EP patients. Here, we provide a comprehensive review of the background of EP, assess the available clinical data on the efficacy of targeted therapies, and aim to provide a foundation for clinical decision making for this rare form of psoriasis.
Topics: Dermatitis, Exfoliative; Dermatologic Agents; Humans; Psoriasis
PubMed: 32180204
DOI: 10.1007/s40265-020-01283-2 -
Farmacia Hospitalaria : Organo Oficial... 2023The objective of this review is to gather the available evidence on the different drugs used in immune-mediated inflammatory diseases in pregnancy, lactation, their... (Review)
Review
OBJECTIVE
The objective of this review is to gather the available evidence on the different drugs used in immune-mediated inflammatory diseases in pregnancy, lactation, their influence on female and male fertility, advice on discontinuation before conception and to help in routine clinical practice for better patient advice on family planning.
METHODS
A bibliographic search was carried out, where published articles (review studies, observational studies and case series) in English or Spanish until April 2020 that analyzed the management of pregnancy, lactation and/or fertility in patients on treatment in immune-mediated diseases were selected.
RESULTS
A total of 95 references were selected and the information on each drug was synthesized in tables. Drugs contraindicated in pregnancy are topical retinoids, pimecrolimus, cyclooxygenase 2 inhibitors, methotrexate, mycophenolate mofetil, leflunomide, acitretin, and thiopurines. The lack of data advises against the use of apremilast, tofacitinib, baricitinib, anakinra, abatacept, tocilizumab and the new biologicals. Topical salicylates, paracetamol, ultraviolet therapy and hydroxychloroquine treatment are safe, and anti-TNF biological therapy are considered low risk, with certolizumab being the drug of choice throughout pregnancy and lactation. Most are compatible with paternal exposure except for sulfasalazine, mycophenolate and leflunomide, for which suspension of treatment prior to conception is recommended, and cyclosporine with dose requirements of less than 2 mg/kg/day.
CONCLUSIONS
In this context of chronic treatments with teratogenic potential, it is necessary to highlight the importance of pregnancy planning to select the safest drug. Given the quality of the available data, it is still necessary to continuously update the information, as well as to promote observational studies of cohorts of pregnant patients and men of childbearing age, including prospective studies, in order to generate more scientific evidence.
Topics: Pregnancy; Humans; Male; Female; Antirheumatic Agents; Breast Feeding; Leflunomide; Prospective Studies; Tumor Necrosis Factor Inhibitors; Immunosuppressive Agents; Fertility
PubMed: 36732114
DOI: 10.1016/j.farma.2022.12.016 -
Lupus Apr 2022The treatment of discoid lupus erythematosus (DLE) is often challenging, especially in patients who are refractory or intolerant to topical treatments and first-line...
BACKGROUND
The treatment of discoid lupus erythematosus (DLE) is often challenging, especially in patients who are refractory or intolerant to topical treatments and first-line systemic drugs, specifically antimalarial drugs. Although acitretin has been shown to be effective in patients with DLE in a few studies, there is no published study describing the long-term efficacy of acitretin with a validated score.
OBJECTIVES
To evaluate the efficacy and safety of acitretin in patients with antimalarial-refractory/intolerant DLE.
METHODS
A prospective, open-label, uncontrolled study was conducted in patients with antimalarial-refractory/intolerant DLE. All patients were treated with an initial dosage of 10 mg acitretin daily. Clinical response was assessed using the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) at weeks 4, 8, 12, and 24. Acitretin was increased to 25 mg daily unless an adequate response was achieved at week 8.
RESULTS
Fourteen patients were recruited. Of these, 10 were antimalarial-refractory and four were antimalarial-intolerant. The acitretin therapy was discontinued in one patient after 20 weeks of treatment because of active systemic disease. Of the 13 remaining patients, the mean RCLASI activity scores declined from 21 ± 9 at baseline to 9 ± 4 at week 24. A significant reduction in RCLASI was initially observed at week four and consistently noted at each follow-up visit ( ≤ 0.01). At the end of the study, a marked response was achieved in approximately 80% of patients. There were no statistically significant differences in the clinical response or in the requirement of the up-dosing of acitretin between the refractory and intolerance groups ( = 0.88 and = 0.326, respectively). Age ≥50 years old, female sex, and generalized DLE were the favorable prognostic factors. No serious adverse events were noted.
CONCLUSIONS
Acitretin appears to be an effective treatment with acceptable safety profiles for antimalarial-refractory/intolerant DLE.
Topics: Acitretin; Antimalarials; Female; Humans; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Middle Aged; Prospective Studies
PubMed: 35306922
DOI: 10.1177/09612033221086878 -
AAPS PharmSciTech May 2021Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis... (Review)
Review
Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis include methotrexate (MTX), cyclosporine (CsA), acitretin, dexamethasone, and salicylic acid. However, conventional formulations due to poor absorptive capacity, inconsistent drug release characteristics, poor capability of selective targeting, poor retention of drug molecules in target tissue, and unintended skin reactions restrict the clinical efficacy of drugs. Advances in topical nanocarriers allow the development of prominent drug delivery platforms can be employed to address the critical issues associated with conventional formulations. Advances in nanocarriers design, nano-dimensional configuration, and surface functionalization allow formulation scientists to develop formulations for a more effective treatment of psoriasis. Moreover, interventions in the size distribution, shape, agglomeration/aggregation potential, and surface chemistry are the significant aspects need to be critically evaluated for better therapeutic results. This review attempted to explore the opportunities and challenges of current revelations in the nano carrier-based topical drug delivery approach used for the treatment of psoriasis.
Topics: Administration, Cutaneous; Animals; Cyclosporine; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Liposomes; Methotrexate; Nanocapsules; Psoriasis; Salicylic Acid
PubMed: 34041632
DOI: 10.1208/s12249-021-02057-z