RESUMEN
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Interleukin (IL) 13 is a type 2 cytokine that is key to the inflammation underlying AD. Tralokinumab is a first-in-class, fully human, monoclonal antibody that specifically binds with high affinity to IL-13, neutralizing it in AD. Immunomodulatory treatments may impair vaccine-induced immune responses. OBJECTIVE: Assess the immune responses to standard vaccines in adults with moderate-to-severe AD who are undergoing treatment with tralokinumab. METHODS: ECZema TRAlokinumab Trial No. 5 (ECZTRA 5; NCT03562377) was a phase 2, double-blind, randomized, placebo-controlled trial taking place over 30 weeks. Eligible adults were randomized 1:1, with 107 patients receiving tralokinumab 300 mg and 108 patients receiving a placebo every 2 weeks for 16 weeks. All patients received Tdap (tetanus/diphtheria/pertussis) and meningococcal vaccines at week 12. The primary end points were positive antitetanus and antimeningococcal responses between weeks 12 and 16 (noninferiority margin, -25%; responder, >3-fold increase in IgG). RESULTS: The noninferiority of tralokinumab versus placebo for immune response to Tdap (91.9% vs 96.1%) and meningococcal (86.0% vs 84.2%) vaccines was demonstrated at week 16. During treatment, the rates of adverse events were lower for tralokinumab than for the placebo, with most events being mild or moderate. LIMITATIONS: Responses to other vaccines (including influenza) were not examined. CONCLUSIONS: Treatment with tralokinumab 300 mg every 2 weeks did not affect immune responses to Tdap and meningococcal vaccines. Treatment was well tolerated when administered concomitantly with the vaccines and demonstrated a safety profile comparable to phase 3 trials.
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Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacunas Meningococicas/inmunología , Adulto , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
13-cis-retinoic acid (13-cRA) is a safe treatment for severe acne, as it has immunomodulatory effects such as enhancing the antigen-presenting activity of epidermal Langerhans cells (LCs) and T-cell activity. The aim of this study was to prospectively show the alteration of sensitization and irritation reactions in acne patients undergoing 13-cRA therapy. This cross-sectional descriptive study consisted of 65 severe to refractory acne patients. The standard thin-layer rapid-use epicutaneous test (T.R.U.E. test) was used to screen sensitization and irritation reactions before and after 3-month 13-cRA treatment. Patch test results after 13-cRA therapy revealed an increase in newly formed sensitization and irritation reactions. Sensitization rate was significantly higher (43.1%) in the second patch test, when compared with the first patch test results (27.7%; P = 0.002). No statistical difference was found in irritation rates. In this study, the sensitization rate was higher after treatment, which could be attributed to the greater antigen penetration due to the disrupted barrier and/or the upregulation of antigen-presenting activity in LC. This would cause a more prominent immune reaction to antigens. Based on these findings, we suggest that 13-cRA may have a sensitization effect, and physicians should be aware of this complication due to 13-cRA treatment. (SKINmed. 2021;19:-0).
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Fármacos Dermatológicos/efectos adversos , Hipersensibilidad/epidemiología , Isotretinoína/efectos adversos , Adolescente , Presentación de Antígeno/inmunología , Antígenos/inmunología , Estudios Transversales , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/inmunología , Femenino , Humanos , Hipersensibilidad/inmunología , Isotretinoína/administración & dosificación , Isotretinoína/inmunología , Células de Langerhans/inmunología , Masculino , Pruebas del Parche , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Tripterygium wilfordii Hook. f. (TwHf) belonging to the Celastraceae family is widely used for psoriasis treatment, especially in topical therapy in Chinese traditional medicine. PURPOSE: In this study, we investigated the anti-psoriatic effects of topical administration of Tripterygium wilfordii Hook. f. root decoction (TwHf-RD), as well as its safety and potential mechanisms of action in vivo and in vitro. METHODS: Psoriasis-like lesions were induced in mice using imiquimod (IMQ). The liver and kidney function and the pathological changes in the liver, kidney, and spleen were measured using ELISA and hematoxylin and eosin (H&E) staining after TwHf-RD treatment. H&E staining was used to determine the optimum concentration of TwHf-RD. The expression levels of ki67 and apoptosis related-factors in vivo and in vitro were measured by immunohistochemical staining, flow cytometry, and western blotting. Immunocyte differentiation and pro-inflammatory cytokine (IL-17A, IL-17F, IL-10, IL-22, IL-23, IFN-γ, and TNF-α) expression levels were determined by flow cytometry and RT-qPCR. RESULTS: TwHf-RD treatment attenuated skin inflammation, inhibited keratinocyte (KC) proliferation, increased the levels of apoptosis factors, and influenced the differentiation and inflammatory response of T lymphocytes and regulatory T cells in mice. In vitro experiments proved that Tripterygium wilfordii Hook. f. root extract (TwHf-RE) regulates the proliferation and apoptosis of PAM212 cells. CONCLUSION: TwHf-RD alleviates IMQ-induced psoriasis lesions by regulating the proliferation and apoptosis of KC and immune cells and by inhibiting immunocyte differentiation and pro-inflammatory cytokine expression.
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Antiinflamatorios no Esteroideos/inmunología , Fármacos Dermatológicos/farmacología , Queratinocitos/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Tripterygium/química , Administración Tópica , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas/metabolismo , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/química , Fármacos Dermatológicos/inmunología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Imiquimod/toxicidad , Masculino , Ratones Endogámicos BALB C , Raíces de Plantas/química , Psoriasis/inducido químicamente , Psoriasis/patología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunologíaAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Dermatitis/tratamiento farmacológico , Fármacos Dermatológicos/efectos adversos , Psoriasis/inducido químicamente , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis/inmunología , Dermatitis/patología , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/inmunologíaRESUMEN
Atopic dermatitis (AD) is a prevalent inflammatory skin condition that, depending on its severity, can cause enormous morbidity. Corticosteroids and systemic immunosuppression, traditionally standard of care for difficult-to-treat disease, have many undesirable side effects. The desire for targeted treatments along with an improved understanding of the pathophysiology of AD has spurred the development of novel treatments. In this article, we review promising new treatments and discuss how their targets-IL-13, IL-31, OX40 (CD134), and the Janus kinase family of proteins-participate in the pathogenesis of AD. We review the published phase II and III data for dupilumab, tralokinumab, lebrikizumab, nemolizumab, anti-OX40 antibody, baricitinib, abrocitinib, and upadacitinib. The introduction of new agents may offer new options, but it remains to be seen how narrow-acting agents, like single interleukin inhibitors, will compare in safety and efficacy to broad-acting agents such as JAK inhibitors.
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Dermatitis Atópica , Fármacos Dermatológicos , Inhibidores de Puntos de Control Inmunológico/farmacología , Terapia Molecular Dirigida , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/inmunología , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/farmacología , Drogas en Investigación , Humanos , Inhibidores de las Cinasas Janus/farmacología , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/tendenciasRESUMEN
Isatis tinctoria L. (woad) has been used in medicine for centuries and has demonstrated anti-inflammatory effects. However, to date, no well-defined extracts with precise analysis of active substances have been developed. The aim of this study was to develop novel extracts of Isatis tinctoria L., and to characterize their active ingredients and anti-inflammatory properties. Various extracts of Isatis tinctoria L. were analysed for their active ingredients, and screened for anti-inflammatory effects using cyclooxygenase-2 activity assays. A petroleum ether extract was found to have the best effects, and was tested in a mouse model of acute allergic contact dermatitis. In the mouse model the petroleum ether extract resulted in significantly reduced ear swelling, oedema and inflammatory cell density. In mouse skin and human keratinocyte cultures, petroleum ether extract inhibited pro-inflammatory cytokine expression. Furthermore, human mast cell degranulation was significantly inhibited in LAD2 cell cultures. In conclusion, novel woad extracts were developed and shown to have anti-inflammatory properties in a contact hypersensitivity animal model and human keratinocytes. The production of such extracts and further characterization of their specific properties will enable determination of their potential dermatological effects in the treatment of inflamed and irritated skin.
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Antiinflamatorios/uso terapéutico , Dermatitis Alérgica por Contacto/tratamiento farmacológico , Isatis , Fitoterapia , Extractos Vegetales/uso terapéutico , Administración Tópica , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/inmunología , Células Cultivadas , Dermatitis Alérgica por Contacto/inmunología , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/uso terapéutico , Modelos Animales de Enfermedad , Oído , Humanos , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/inmunología , Interleucina-33/antagonistas & inhibidores , Interleucina-33/inmunología , Interleucina-6/antagonistas & inhibidores , Interleucina-6/inmunología , Queratinocitos/efectos de los fármacos , Queratinocitos/inmunología , Estabilizadores de Mastocitos/administración & dosificación , Estabilizadores de Mastocitos/inmunología , Estabilizadores de Mastocitos/uso terapéutico , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Piel/efectos de los fármacos , Piel/inmunología , Piel/patologíaAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Adulto , Anticuerpos Monoclonales Humanizados/inmunología , Dermatitis Atópica/inmunología , Fármacos Dermatológicos/inmunología , Humanos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy. OBJECTIVE: To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment. METHODS: Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed. RESULTS: Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab. LIMITATIONS: Retreatment could be assessed in only 1 phase 3 brodalumab study. CONCLUSION: Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/epidemiología , Reacción en el Punto de Inyección/epidemiología , Psoriasis/tratamiento farmacológico , Anticuerpos/sangre , Anticuerpos/inmunología , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/inmunología , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/inmunología , Relación Dosis-Respuesta Inmunológica , Esquema de Medicación , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/inmunología , Humanos , Reacción en el Punto de Inyección/sangre , Reacción en el Punto de Inyección/inmunología , Inyecciones Subcutáneas , Psoriasis/diagnóstico , Psoriasis/inmunología , Retratamiento/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Piel/efectos de los fármacos , Piel/inmunología , Resultado del Tratamiento , Ustekinumab/administración & dosificación , Ustekinumab/efectos adversos , Ustekinumab/inmunologíaRESUMEN
Molecular analysis is key to a better understanding of drug resistance during therapy. The aim of this study was to evaluate changes in the expression of tumor necrosis factor α (TNF-α), interleukin (IL)-IL12A, IL12B, IL23A, interferon gamma (IFN-γ) in psoriatic patients during 84 days of treatment and TNF-α on the protein level. The study group consisted of 32 psoriatic patients during cyclosporine A therapy. The molecular analysis was made by using real-time reverse transcription polymerase chain assay (RTqPCR) and MALDI ToF mass spectroscopy three times: after 0, 42, 84 days of treatment. Statistically significant differences (p < .05) in transcriptional activity were observed for genes: TNF-α (0 vs. 42nd days p = .006; 0 vs. 84th days p = .005), IL23A (0 vs. 42nd days p = .041), IFN-γ (0 vs. 42th days p = .040; 0 vs. 84th days p = .041), IL17 (0 vs. 42nd p = .000003 0 vs. 84th p = .001650), IL12A (0 vs. 42nd p = .0047 vs. 84th p = .0063). The expression of TNF-α was downregulated during therapy, IL23A was upregulated during CsA treatment, while the expression of IFN-γ and IL17 were higher after 42 days and lower after 84 days compared to 0 days of CsA treatment. It seems that TNF-α, IL12A, IL23A, IFN-γ, and IL17 can be useful complementary molecular markers to assess the efficacy of psoriasis treatment.
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Ciclosporina/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Inmunosupresores/administración & dosificación , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/inmunología , Ciclosporina/inmunología , Fármacos Dermatológicos/inmunología , Regulación de la Expresión Génica , Humanos , Inmunosupresores/inmunología , Interleucina-12/inmunología , Interleucina-23/inmunología , Psoriasis/genética , Psoriasis/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
Introduction: Psoriasis is a chronic inflammatory disease and affects about 10% of the world's population. Psoriasis is associated with a number of comorbidities. Biologic therapies for the treatment of moderate-severe plaque psoriasis include tumor necrosis factor α inhibitors (TNFi), and newer molecules targeting IL-12 and 23, blocking p40 subunit, or targeting subunit p19 of IL-23 and other molecules blocking IL-17A, or directed against the IL-17 receptor. Areas covered: Anti-interleukin drugs show great improvement in disease control and on the other hand are not affected by important adverse reactions of older compounds. Approach to chronic disease affected patients, in particular, and to patients with multiple comorbidities is revolutionized by novel molecules that are safer and more manageable. Expert opinion: A recent work suggests that pro-fibrogenic cytokines, IL-17, might be important player of liver damage and even in regulation of obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Choosing to interfere with IL-23/Il-17 axis, definitely, is like acting against psoriatic march and in a parallel way against its comorbidities.
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Anticuerpos Monoclonales/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Productos Biológicos/administración & dosificación , Productos Biológicos/efectos adversos , Productos Biológicos/inmunología , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Humanos , Interleucina-12/inmunología , Interleucina-17/inmunología , Interleucina-23/inmunología , Psoriasis/inmunología , Psoriasis/patología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, a key cytokine involved in psoriasis and psoriatic arthritis development, and has shown rapid and long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. Monoclonal antibody therapies may be associated with the production of treatment-emergent antidrug antibodies (TE-ADAs) that can affect drug pharmacokinetics, diminish clinical responses via inhibition of target binding or cause hypersensitivity reactions. Secukinumab exhibited minimal immunogenicity up to 52 weeks in patients with moderate-to-severe plaque psoriasis, as evidenced by TE-ADA in <1% patients. OBJECTIVE: To investigate the immunogenicity of secukinumab treatment up to 5 years in two phase 3 extension studies (NCT01640951 and NCT01365455) in patients with moderate-to-severe plaque psoriasis. METHODS: Immunogenicity was evaluated up to Week 268 (5 years). TE-ADAs were defined as positive antidrug antibody (ADA) signals detected in post-treatment samples from patients with negative baseline signals. Confirmed positive samples were further analysed for their neutralizing potential. RESULTS: In total, 1821 patients entered the extension studies. Among patients receiving secukinumab and evaluated for ADAs (n = 1636), 32 developed TE-ADA, which resulted in an incidence of new TE-ADA cases below 1% per year. Neutralizing antibodies were detected in 9/32 (28%) patients with TE-ADA. Half of ADA-positive cases were transient. Among pharmacokinetic samples measured at the times of immunogenicity determination (n = 9992), 544 (5.4%) had secukinumab concentrations higher than the drug tolerance level of 53.8 µg/mL. There was no effect of TE-ADA, including neutralizing antibodies, on efficacy, safety or pharmacokinetics of secukinumab. CONCLUSION: The yearly secukinumab immunogenicity incidence over 5 years of treatment was consistently below 1% in patients with moderate-to-severe plaque psoriasis. Any TE-ADAs, including neutralizing antibodies, were not associated with loss of secukinumab efficacy or with clinical concerns.
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Anticuerpos Monoclonales Humanizados/inmunología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Esquema de Medicación , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Colitis/inmunología , Infliximab/uso terapéutico , Melanoma/tratamiento farmacológico , Nocardiosis/diagnóstico , Receptor de Muerte Celular Programada 1/inmunología , Anciano , Colitis/inducido químicamente , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/uso terapéutico , Humanos , Infliximab/efectos adversos , Infliximab/inmunología , Masculino , Melanoma/genética , Mutación , Nocardiosis/inducido químicamente , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, is efficacious for moderate to severe plaque psoriasis. We examined relationships between serum ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADAs), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks. During the long-term extension period dosage of 80 mg every 4 weeks, stable serum trough concentrations maintained high clinical responses through week 60. Most (82.6%, 308/373) patients never developed TE-ADA. In TE-ADA-positive patients (17.4%, n = 65), variations in ADA titers, neutralizing capacity, and persistence were observed. Fifty-six patients (15%) developed low or moderate maximum titers, with serum concentrations and efficacy comparable to those of TE-ADA-negative patients. Nine patients (2.4%) developed high titers, with variable individual clinical responses; four of these nine patients achieved at least PASI 75 at week 60. Median serum concentrations in the TE-ADA-high titer group were generally comparable to the median serum concentrations in the lower titer groups. For most patients, TE-ADA had a negligible impact on ixekizumab serum concentrations and efficacy. Clinicaltrials.gov: NCT01646177.
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Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales/inmunología , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/inmunología , Formación de Anticuerpos , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/farmacocinética , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Interleucina-17/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Psoriasis/sangre , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales/inmunología , Dermatitis Atópica/tratamiento farmacológico , Fármacos Dermatológicos/inmunología , Huésped Inmunocomprometido/inmunología , Pruebas del Parche , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Fármacos Dermatológicos/administración & dosificación , Femenino , Humanos , Persona de Mediana EdadRESUMEN
INTRODUCTION: Rheumatoid arthritis is a common inflammatory joint disease with a myriad of systemic manifestations. Over the last 20 years its treatment has been revolutionised by the introduction of a number of different biologic drugs, including the TNF-receptor Fc fusion protein, Etanercept. However, these drugs are expensive and their widespread use puts a financial burden on healthcare systems. As many biologic treatments begin to come off patent new 'biosimilar' versions are being developed which can lead to significant cost savings. GP2015 (Erelzi®) is the second biosimilar version of Etanercept which is licensed for the treatment of rheumatoid arthritis. Areas covered: We discuss the Chemistry, pharmacokinetics and pharmacodynamics of GP2015 in relation to reference Etanercept. Preclinical trials have shown pharmacokinetic equivalence between GP2015 and the reference drug. The recently completed Phase III, randomised, double blind EQUIRA study has shown equivalent efficacy and safety between GP2015 and Etanercept in patients with rheumatoid arthritis. Expert opinion: GP2015 has shown equivalent efficacy and safety to reference Etanercept. With a growing number of biosimilar medications becoming available and another biosimilar Etanercept already being widely prescribed it is likely to be the cost of the drug that will determine if it is used widely.
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Artritis Reumatoide/tratamiento farmacológico , Biosimilares Farmacéuticos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Etanercept/uso terapéutico , Anticuerpos Antiidiotipos/sangre , Artritis Reumatoide/patología , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacocinética , Ensayos Clínicos como Asunto , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Fármacos Dermatológicos/farmacocinética , Etanercept/efectos adversos , Etanercept/inmunología , Etanercept/farmacocinética , Semivida , Humanos , Linfotoxina-alfa/inmunología , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory rheumatic disease that manifests itself with synovitis, dactylitis, enthesitis and also axial involvement. Interleukin-17A has been identified as a master cytokine in the inflammatory response and pathogenesis of PsA and spondyloarthritis in general. Ixekizumab is a new humanized monoclonal antibody that blocks the biological activity of IL-17A. This biological agent has previously demonstrated a high level of efficacy in psoriasis. Areas covered: This review discusses the basic immunology of the IL-17 cytokine family, the contribution of IL-17A to the immunopathogenesis of PsA, the clinical trials that evaluated ixekizumab in patients with PsA (SPIRIT program) and the safety of this agent. Expert opinion: Ixekizumab demonstrated its efficacy in different aspects of PsA including peripheral joint involvement, dactylitis, skin symptoms and patient reported outcomes in the 2 phase III trials from the SPIRIT program. Its safety profile was consistent with previous observations in patients with psoriasis. The role of IL-17A in the management of patients with PsA needs further clarification. According to EULAR recommendations for the management of PsA, IL-17A inhibitors may be used as second line biological DMARDs after TNF inhibitors.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Interleucina-17/inmunología , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/inmunología , Artritis Psoriásica/patología , Ensayos Clínicos como Asunto , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Humanos , Interleucina-17/metabolismo , Infecciones del Sistema Respiratorio/etiología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: EGALITY was a phase III confirmatory efficacy and safety study conducted in patients with plaque-type psoriasis as a part of totality of evidence gathered during the development of GP2015, an etanercept biosimilar. OBJECTIVE: To demonstrate equivalent efficacy and comparable safety and immunogenicity of GP2015 and the etanercept originator product (ETN, Enbrel® ) and evaluate effects of repeated switching between GP2015 and ETN. Results for efficacy, safety and immunogenicity during treatment period (TP) 2 (TP2) are presented pooling the two continued treatment arms (pooled continued) versus the two treatment arms with repeated switches (pooled switched). METHODS: Patients (n = 531) were randomized 1:1 to self-administer GP2015 or ETN twice-weekly subcutaneously during TP1. Patients with a ≥50% improvement in Psoriasis Area and Severity Index (PASI 50) at week 12 were re-randomized for TP2 to continue the same treatment at once-weekly dosing or to undergo three consecutive treatment switches between GP2015 and ETN until week 30. Patients continued the last-assigned treatment during TP2, until week 52. RESULTS: Mean (standard deviation [SD]) PASI scores at baseline were similar in patients who underwent multiple switches compared to those with continued treatments during TP2. During TP2, PASI 50, PASI 75 and PASI 90 response rates, percent change from baseline in PASI scores and all other efficacy parameters were similar between the pooled switched and pooled continued treatment groups at all time points. The incidence of treatment-emergent adverse events including injection site reactions was comparable between the pooled switched (36.7%) and pooled continued (34.9%) groups. None of the patients in either treatment group were positive for binding anti-drug antibodies in TP2. CONCLUSION: Treatment efficacy, safety and immunogenicity were similar between the pooled continued and pooled switched treatments during TP2, indicating that there are no effects in the short term on clinical data of multiple switches between GP2015 and ETN.
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Biosimilares Farmacéuticos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Etanercept/uso terapéutico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Adulto , Anticuerpos/inmunología , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Enfermedad Crónica , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/inmunología , Método Doble Ciego , Esquema de Medicación , Etanercept/administración & dosificación , Etanercept/efectos adversos , Etanercept/análogos & derivados , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana EdadRESUMEN
The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor-α inhibitors; infliximab and adalimumab, one anti-interleukin (IL)-12/23p40 antibody; ustekinumab, and IL-17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti-IL-17A antibodies. Brodalumab is an anti-IL17RA antibody. In this review, we pick up topics which have drawn attention regarding the safety of biologics and discuss them with recent published work.