OBJECTIVE: Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis.
METHODS OF LITERATURE SEARCH: By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality.
RESULTS: Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases.
LIMITATIONS: Our results are limited by the lack of data from RCTs.
CONCLUSION: Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.
OBJECTIVE: To perform an update of a review of the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA).
METHODS: This is a systematic literature research of 2015-2018 publications on all DMARDs in patients with PsA, searching Medline, Embase and the Cochrane Library. Efficacy was assessed in randomised controlled trials. For safety, cohort studies, case-control studies and long-term extensions (LTEs) were analysed.
RESULTS: 56 publications (efficacy: n=33; safety n=23) were analysed. The articles were on tumour necrosis factor (TNF) inhibitors (n=6; golimumab, etanercept and biosimilars), interleukin (IL)-17A inhibitors (n=10; ixekizumab, secukinumab), IL-23-p19 inhibitors (n=2; guselkumab, risankizumab), clazakizumab (IL-6 inhibitor), abatacept (CD80/86 inhibitor) and ABT-122 (anti-TNF/IL-17A), respectively. One study compared ustekinumab (IL-12/23i) with TNF inhibitor therapy in patients with entheseal disease. Three articles investigated DMARD tapering. Trials on targeted synthetic DMARDs investigated apremilast (phosphodiesterase-4 inhibitor) and Janus kinase inhibitors (JAKi; tofacitinib, filgotinib). Biosimilar comparison with bio-originator showed non-inferiority. Safety was evaluated in 13 LTEs, 9 cohort studies and 1 case-control study investigating malignancies, infections, infusion reactions, multiple sclerosis and major cardiovascular events, as well as efficacy and safety of vaccination. No new safety signals were identified; however, warnings on the risk of venous thromboembolic events including pulmonary embolism when using JAKi were issued by regulators based on other studies.
CONCLUSION: Many drugs in PsA are available and have demonstrated efficacy against placebo. Efficacy varies across PsA manifestations. Safety must also be taken into account. This review informed the development of the European League Against Rheumatism 2019 updated PsA management recommendations.
OBJECTIVES: To determine the efficacy of biologics in preventing radiographic progression in peripheral joints of PsA patients.
METHODS: Studies were searched in MEDLINE, Web of Science, and abstracts from the last three EULAR and ACR meetings up to 31 December 2019. Primary and secondary endpoints were the proportion of patients without radiographic progression and the mean change in total radiographic score at week 24.
RESULTS: Eleven studies, involving 5382 patients, 9 drugs and 18 treatments, were included. Patients receiving biologics were more likely to achieve radiographic non-progression compared with placebo [odds ratio: pooled: 2.40, 95% CI: 2.00, 2.87; TNF inhibitors (TNFi): 2.94, 95% CI: 2.38, 3.63; IL inhibitors (ILi): 2.15, 95% CI: 1.69, 2.74; abatacept: 1.54, 95% CI: 1.03, 2.28] and have significantly lower radiographic progression [standardized mean difference (SMD): pooled: -2.16, 95% CI: -2.91, -1.41; TNFi: -2.82, 95% CI: -4.31, -1.33; ILi: -1.60, 95% CI: -2.49, -0.72; abatacept: -0.40, 95% CI: -0.59, -0.21]. Concomitant MTX therapy was not superior to monotherapy (SMD: pooled: 0.01, 95% CI: -0.07, 0.08; biologics: 0.01, 95% CI: -0.09, 0.11; placebo: -0.01, 95% CI: -0.13, 0.12). The effect of ustekinumab and secukinumab on radiographic progression was not influenced by prior anti-TNF therapy (SMD: -0.08, 95% CI: -0.25, 0.10).
CONCLUSION: Biologic agents may retard radiographic progression in PsA patients in terms of bone erosion and joint space narrowing compared with placebo. MTX seems to have no added effect. Prior anti-TNF therapy seems to not influence the radiographic efficacy of IL blockers.
El reconocimiento del papel central de la interleuquina 17A (IL-17A) en la patogénesis de la psoriasis ha llevado al desarrollo de varios anticuerpos monoclonales dirigidos a esta citoquina oa sus receptores con fines terapéuticos. IL-17A también juega un papel importante en la protección inmunológica contra las infecciones, especialmente las debidas a Candida sp., Como lo demuestran los hallazgos en pacientes con defectos genéticos en las respuestas inmunes relacionadas con IL-17. Para evaluar el potencial del tratamiento anti-IL-17 para promover las infecciones por Candida, aquí hemos revisado sistemáticamente los ensayos clínicos publicados de pacientes con psoriasis o artritis psoriásica. En el 4,0% de los pacientes tratados con brodalumab, el 2,1% con secukinumab y el 3,3% con el ixekizumab se notificaron infecciones por Candida, frente al 0,3%, 2,3% y 0,8% de los asignados al placebo, ustekinumab o etanercept, respectivamente. Aunque se encontró que la incidencia de la infección por Candida aumentó en un solo grado pequeño durante la terapia anti-IL-17, los pacientes sometidos a dicho tratamiento deben ser monitorizados para detectar la infección por hongos y tratados según sea necesario. Nos proponemos adoptar las recomendaciones recientemente actualizadas para el manejo práctico de la infección por Candida en pacientes tratados con inhibidores de IL-17. Este artículo está protegido por derechos de autor. Todos los derechos reservados.
Although biologics are highly effective in the treatment of psoriasis, some patients consistently fail monotherapy. For these patients, combination therapy is commonly employed. However, evidence-based recommendations for combination therapy in the treatment of psoriasis with interleukin-17 (IL-17) inhibitors are currently lacking. Therefore, we aimed to conduct a systematic review of existing literature discussing the efficacy and safety of IL-17 inhibitors in combination with other therapeutic modalities in the treatment of psoriasis.
METHODS OF LITERATURE SEARCH:
By way of a search of PubMed, Cochrane, and Web of Science databases in March 2021, we identified peer-reviewed articles with data on the safety and/or efficacy of IL-17 inhibitor combination therapies in adults with psoriasis and/or psoriatic arthritis (PsA). A modified version of the 2011 Oxford Centre for Evidence-Based Medicine Scheme was utilized for assessing study quality.
RESULTS:
Twenty-four articles with a total of 3,154 patients met inclusion/exclusion criteria. These articles comprised six post-hoc/subgroup analyses of randomized controlled trials (RCTs), four uncontrolled clinical trials, three case series, and 11 case reports that provided data on IL-17 inhibitor therapy in combination with conventional disease-modifying antirheumatic drugs (cDMARDs), apremilast, acitretin, topical therapy, phototherapy, and/or medications for comorbid diseases.
LIMITATIONS:
Our results are limited by the lack of data from RCTs.
CONCLUSION:
Although cDMARDs are often used in psoriasis combination therapies, the current literature suggests concomitant cDMARDs with IL-17 inhibitor therapy provides no added benefit compared to IL-17 inhibitor monotherapy. However, IL-17 inhibitor in combination with apremilast or acitretin shows efficacy and safety in case series/reports and may allow for a reduction in medication dosing and/or frequency, thereby minimizing costs and adverse events. Future RCTs investigating IL-17 inhibitor therapy in combination with acitretin or apremilast are warranted.
