Asunto(s)
Hidradenitis Supurativa , Psoriasis , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/inducido químicamente , Humanos , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/efectos adversos , Adalimumab/uso terapéuticoAsunto(s)
Hidradenitis Supurativa , Imidazoles , Enfermedades Inflamatorias del Intestino , Tetrazoles , Humanos , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Diagnóstico Diferencial , Imidazoles/efectos adversos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Tetrazoles/efectos adversos , Femenino , Masculino , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , AdultoRESUMEN
Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal.
Asunto(s)
Productos Biológicos , Hidradenitis Supurativa , Infecciones Oportunistas , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/epidemiología , Hidradenitis Supurativa/inducido químicamente , Productos Biológicos/efectos adversos , Calidad de Vida , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Infecciones Oportunistas/epidemiología , Factores Inmunológicos/efectos adversosAsunto(s)
Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/complicaciones , Inhibidores y Moduladores de Gamma Secretasa , Secretasas de la Proteína Precursora del Amiloide/genética , Glicoproteínas de Membrana/genética , MutaciónRESUMEN
BACKGROUND & AIMS: Tumor necrosis factor inhibitors (anti-TNF) are effective therapies for several immune-mediated inflammatory diseases (IMIDs). However, case reports have identified the paradoxical occurrence of IMIDs in patients treated with anti-TNF. We studied the risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa after the initiation of anti-TNF therapy for inflammatory bowel disease (IBD). METHODS: We conducted 2 nationwide cohort studies comprising all patients with IBD in Denmark (2005-2018) and France (2008-2018). We obtained individual-level information on exposure to anti-TNF, diagnoses of IMIDs including rheumatoid arthritis, psoriasis, and hidradenitis suppurativa, and potential confounders from healthcare registers in the respective countries. We used Cox models to estimate hazard ratios (HRs) for the association between anti-TNF exposure and IMIDs and then pooled the estimates from the 2 cohorts. To test the robustness of our results, we performed an active comparator analysis of anti-TNF monotherapy vs azathioprine monotherapy. RESULTS: The Danish and French cohorts comprised 18,258 and 88,786 subjects with IBD, respectively, contributing a total of 516,055 person-years of follow-up. Anti-TNF was associated with an increased risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa in both the Danish (HR, 1.66; 95% confidence interval [CI], 1.34-2.07) and the French cohort (HR, 1.78; 95% CI, 1.63-1.94), with a pooled HR of 1.76 (95% CI, 1.63-1.91). Anti-TNF was also associated with an increased risk of the outcomes when compared with azathioprine (pooled HR, 2.94; 95% CI, 2.33-3.70). CONCLUSIONS: In 2 nationwide cohorts of IBD patients, anti-TNF therapy was associated with an increased risk of rheumatoid arthritis, psoriasis, and hidradenitis suppurativa.
Asunto(s)
Artritis Reumatoide , Hidradenitis Supurativa , Enfermedades Inflamatorias del Intestino , Psoriasis , Humanos , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Azatioprina/efectos adversos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Factor de Necrosis Tumoral alfa , Enfermedades Inflamatorias del Intestino/epidemiología , Artritis Reumatoide/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Agentes InmunomoduladoresRESUMEN
BACKGROUND: Acne fulminans (AF) is a rare severe acne entity. Although occasionally reported, it is unclear whether AF development is associated with oral isotretinoin treatment. OBJECTIVES: To investigate the occurrence of isotretinoin-associated AF, clinical characteristics and prognosis at follow-up. METHODS: An international, multicentre, retrospective study was performed in eight hospitals following the call of the EADV Task Force on Acne, Rosacea and Hidradenitis Suppurativa (ARHS). Characteristics of patients treated with isotretinoin before the development of AF (isotretinoin-associated acne fulminans, IAF) were compared with non-IAF (NAF). RESULTS: Forty-nine patients diagnosed with AF from 2008 to 2022 were included (mean age 16.4 years, SD 2.9, 77.6% male). Αrthralgias/arthritis occurred in 11 patients (22.9%). AF occurred without any previous acne treatment in 26.5% of the patients. Overall, 28 patients (57.1%) developed AF after oral isotretinoin intake (IAF group), while the remaining 21 patients (42.9%) developed AF without previous oral isotretinoin administration (NAF group). IAF occurred after a median duration of isotretinoin treatment of 45 days (IQR: 30, 90). Patients with IAF were more frequently male compared to patients with NAF (89.3% vs. 61.9%, respectively, p = 0.023). There were no differences in patients with IAF versus NAF in patient age, the duration of pre-existing acne, a family history of AF, the distribution of AF lesions or the presence of systemic symptoms or arthralgias. Regarding the management of AF, patients with IAF were treated more frequently with prednisolone (96.2%) compared to those with NAF (70%; p = 0.033) and less frequently with isotretinoin (32.1%) compared to NAF (85.7%; p < 0.001). At a median follow-up of 2.2 years, 76.4% of patients were free of AF and scarring was present in all patients. CONCLUSIONS: No specific clinical or demographic characteristics of IAF compared with NAF could be detected, a fact that does not support IAF as a district clinical entity.
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Acné Vulgar , Dermatología , Hidradenitis Supurativa , Rosácea , Venereología , Humanos , Masculino , Adolescente , Femenino , Isotretinoína/efectos adversos , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Estudios Retrospectivos , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/patología , Rosácea/tratamiento farmacológicoRESUMEN
BACKGROUND: Paradoxical psoriasis (PP) has been mainly described in patients receiving tumor necrosis factor-α (TNFα) inhibitors for inflammatory bowel disease or psoriasis vulgaris, while such data in the context of hidradenitis suppurativa (HS) are scarce. The purpose of this study was to demonstrate the course of PP and the underlying HS upon switching from adalimumab to a biologic agent targeting the interleukin (IL)-17/IL-23 axis. METHODS: The electronic medical database of the outpatient department for HS of a tertiary hospital for skin diseases was searched to identify patients with moderate-to-severe HS under treatment with adalimumab, who developed PP and were switched to biological therapy with an IL-17 or IL-23 inhibitor between February 2016 and January 2022. Disease assessment scores were evaluated at baseline, at time of PP development, as well as six and 12 months thereafter. RESULTS: Among the 83 patients who received adalimumab for the treatment of HS between February 2016 and January 2022, 10 patients (12%) developed paradoxical psoriasiform skin reactions after a median time of seven (range, 2-48) months. There were four females (40%) and six males (60%) with a median age of 42.5 (range, 33-56) years. Five patients presented with plaque psoriasis and five with palmoplantar pustulosis, while four had intertriginous and three nail involvement. In most of the patients, HS responded well to adalimumab at onset of PP. Eight patients were changed to secukinumab, one to ustekinumab, and one to risankizumab. HS further improved in all but 2 patients, one receiving secukinumab and one receiving risankizumab. In addition, all patients achieved improvement of PP. CONCLUSION: Despite the small number of patients, this study provides support that patients with adalimumab-induced PP may benefit from biologics targeting the IL-17/IL-23 axis. Further studies are needed to establish the optimal therapeutic strategy of the anti-TNFα-induced PP in the context of HS.
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Productos Biológicos , Hidradenitis Supurativa , Psoriasis , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Adalimumab/efectos adversos , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/patología , Productos Biológicos/efectos adversos , Interleucina-23/efectos adversos , Interleucina-17 , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológicoAsunto(s)
Hidradenitis Supurativa , Humanos , Adalimumab/efectos adversos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Anticuerpos Monoclonales Humanizados/efectos adversos , Antiinflamatorios/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Hidradenitis suppurativa (HS) is a chronic condition with a significant psychological and physical burden but a paucity of effective treatments. Early intervention with adalimumab improves disease outcomes. Two previous studies in Denmark and Northern Ireland have identified a time of 8.2 and 2.9â years, respectively, from first HS systemic/dermatology consultation to commencing a biologic. We aimed to evaluate the time from disease onset and from first specialty HS clinic review to the initiation of biologic therapy. We retrospectively reviewed 34 patients on biologic treatment for HS. The mean diagnostic delay was 12.4â years. The mean time from disease onset to biologic initiation was 14.8â years. Prior to a biologic, patients received a median of 3.3 treatments from the specialty HS clinic. The median time to biologic from first presentation at the specialty HS clinic was 1â year. This is shorter than the therapeutic delay reported in dermatology clinics in Denmark and Northern Ireland, providing evidence on the importance of specialized HS treatment. However, to make an impact with specialized HS care and earlier biologic initiation, diagnostic delay needs to be reduced.
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Productos Biológicos , Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Estudios Retrospectivos , Diagnóstico Tardío , Adalimumab/efectos adversos , Terapia Biológica , Productos Biológicos/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
Psoriasis, an immune-mediated inflammatory disease, affects nearly 125 million people globally. The interleukin (IL)-17A homodimer is a key driver of psoriasis and other autoimmune diseases, including psoriatic arthritis, axial spondyloarthritis, hidradenitis suppurativa, and uveitis. Treatment with monoclonal antibodies (mAbs) against IL-17A provides an improvement in the Psoriasis Area and Severity Index compared to conventional systemic agents. In this study, the Affibodyâ technology was used to identify and optimize a novel, small, biological molecule comprising three triple helical affinity domains, izokibep (previously ABY-035), for the inhibition of IL-17A signaling. Preclinical studies show that izokibep, a small 18.6 kDa IL-17 ligand trap comprising two IL-17A-specific Affibody domains and one albumin-binding domain, selectively inhibits human IL-17A in vitro and in vivo with superior potency and efficacy relative to anti-IL-17A mAbs. A Phase 1 first-in-human study was conducted to establish the safety, pharmacokinetics, and preliminary efficacy of izokibep, when administered intravenously and subcutaneously as single doses to healthy subjects, and as single intravenous and multiple subcutaneous doses to patients with psoriasis (NCT02690142; EudraCT No: 2015-004531-13). Izokibep was well tolerated with no meaningful safety concerns identified in healthy volunteers and patients with psoriasis. Rapid efficacy was seen in all psoriasis patients after one dose which further improved in patients receiving multiple doses. A therapeutic decrease in joint pain was also observed in a single patient with concurrent psoriatic arthritis. The study suggests that izokibep has the potential to safely treat IL17A-associated diseases such as psoriasis, psoriatic arthritis, axial spondyloarthritis, hidradenitis suppurativa, and uveitis.
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Artritis Psoriásica , Hidradenitis Supurativa , Psoriasis , Uveítis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Anticuerpos Monoclonales Humanizados , Psoriasis/tratamiento farmacológico , Uveítis/inducido químicamenteAsunto(s)
Biosimilares Farmacéuticos , Hidradenitis Supurativa , Deficiencia de Mevalonato Quinasa , Psoriasis , Humanos , Adalimumab/efectos adversos , Ustekinumab/efectos adversos , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Biosimilares Farmacéuticos/efectos adversos , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamenteRESUMEN
BACKGROUND: Adalimumab, the only biologic registered for hidradenitis suppurativa, shows clinical response in up to 60% of patients, leaving many patients in need for other treatment options such as surgery. OBJECTIVE: To compare the clinical effectiveness of adalimumab combined with surgery vs adalimumab monotherapy in patients with moderate to severe hidradenitis suppurativa. METHODS: A pragmatic Randomized Controlled Trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean International Hidradenitis Suppurativa Severity Score System reduction after 12 months of treatment with the difference in mean Dermatology Life Quality Index reduction as a key secondary outcome. RESULTS: Thirty-one patients were included per arm. The mean International Hidradenitis Suppurativa Severity Score System at baseline was 23.9 ± 10.7 in the surgery group and 20.9 ± 16.4, in the monotherapy group. After 12 months of treatment the surgery group had a significantly greater reduction in International Hidradenitis Suppurativa Severity Score System compared with the monotherapy group (-19.1 ± 11.3 vs -7.8 ± 11.8, P < .001). Moreover, the surgery group showed a greater reduction in Dermatology Life Quality Index after treatment compared with the monotherapy group (-8.2 ± 6.2 vs -4 ± 7.7, P = .02). LIMITATIONS: The study follow-up was too short to assess surgical recurrence rates. DISCUSSION: Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa.
Asunto(s)
Hidradenitis Supurativa , Humanos , Adalimumab , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/cirugía , Hidradenitis Supurativa/inducido químicamente , Calidad de Vida , Resultado del Tratamiento , Índice de Severidad de la EnfermedadAsunto(s)
Biosimilares Farmacéuticos , Hidradenitis Supurativa , Deficiencia de Mevalonato Quinasa , Psoriasis , Humanos , Adalimumab/uso terapéutico , Ustekinumab/efectos adversos , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Biosimilares Farmacéuticos/efectos adversos , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamenteRESUMEN
BACKGROUND: Few therapeutic options are available for patients with moderate-to-severe hidradenitis suppurativa. We aimed to assess the efficacy of secukinumab in patients with moderate-to-severe hidradenitis suppurativa in two randomised trials. METHODS: SUNSHINE and SUNRISE were identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials done in 219 primary sites in 40 countries. Patients aged 18 years old or older with the capacity to provide written informed consent and with moderate-to-severe hidradenitis suppurativa (defined as a total of ≥5 inflammatory lesions affecting ≥2 distinct anatomical areas) for at least 1 year were eligible for inclusion. Included patients also agreed to daily use of topical over-the-counter antiseptics on the areas affected by hidradenitis suppurativa lesions while on study treatment. Patients were excluded if they had 20 or more fistulae at baseline, had ongoing active conditions requiring treatment with prohibited medication (eg, systemic biological immunomodulating treatment, live vaccines, or other investigational treatments), or met other exclusion criteria. In both trials, patients were randomly assigned (1:1:1) by means of interactive response technology to receive subcutaneous secukinumab 300 mg every 2 weeks, subcutaneous secukinumab 300 mg every 4 weeks, or subcutaneous placebo all via a 2 mL prefilled syringe in a double-dummy method as per treatment assignment. The primary endpoint was the proportion of patients with a hidradenitis suppurativa clinical response, defined as a decrease in abscess and inflammatory nodule count by 50% or more with no increase in the number of abscesses or in the number of draining fistulae compared with baseline, at week 16, assessed in the overall population. Hidradenitis suppurativa clinical response was calculated based on the number of abscesses, inflammatory nodules, draining fistulae, total fistulae, and other lesions in the hidradenitis suppurativa affected areas. Safety was assessed by evaluating the presence of adverse events and serious adverse events according to common terminology criteria for adverse events, which were coded using Medical Dictionary for Regulatory Activities terminology. Both the SUNSHINE, NCT03713619, and SUNRISE, NCT03713632, trials are registered with ClinicalTrials.gov. FINDINGS: Between Jan 31, 2019, and June 7, 2021, 676 patients were screened for inclusion in the SUNSHINE trial, of whom 541 (80%; 304 [56%] women and 237 [44%] men; mean age 36·1 years [SD 11·7]) were included in the analysis (181 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 180 [33%] in the placebo group). Between the same recruitment dates, 687 patients were screened for inclusion in the SUNRISE trial, of whom 543 (79%; 306 [56%] women and 237 [44%] men; mean age 36·3 [11·4] years) were included in the analysis (180 [33%] in the secukinumab every 2 weeks group, 180 [33%] in the secukinumab every 4 weeks group, and 183 [34%] in the placebo group). In the SUNSHINE trial, significantly more patients in the secukinumab every 2 weeks group had a hidradenitis suppurativa clinical response (rounded average number of patients with response in 100 imputations, 81·5 [45%] of 181 patients) compared with the placebo group (60·7 [34%] of 180 patients; odds ratio 1·8 [95% CI 1·1-2·7]; p=0·0070). However, there was no significant difference between the number of patients in the secukinumab every 4 weeks group (75·2 [42%] of 180 patients) and the placebo group (1·5 [1·0-2·3]; p=0·042). Compared with the placebo group (57·1 [31%] of 183 patients), significantly more patients in the secukinumab every 2 weeks group (76·2 [42%] of 180 patients; 1·6 [1·1-2·6]; p=0·015) and the secukinumab every 4 weeks group (83·1 [46%] of 180 patients; 1·9 [1·2-3·0]; p=0·0022) had a hidradenitis suppurativa clinical response in the SUNRISE trial. Patient responses were sustained up to the end of the trials at week 52. The most common adverse event by preferred term up to week 16 was headache in both the SUNSHINE (17 [9%] patients in the secukinumab every 2 weeks group, 20 [11%] in the secukinumab every 4 weeks group, and 14 [8%] in the placebo group) and SUNRISE (21 [12%] patients in the secukinumab every 2 weeks group, 17 [9%] in the secukinumab every 4 weeks group, and 15 [8%] in the placebo group) trials. No study-related deaths were reported up to week 16. The safety profile of secukinumab in both trials was consistent with that previously reported, with no new or unexpected safety findings detected. INTERPRETATION: When given every 2 weeks, secukinumab was clinically effective at rapidly improving signs and symptoms of hidradenitis suppurativa with a favourable safety profile and with sustained response up to 52 weeks of treatment. FUNDING: Novartis Pharma.
Asunto(s)
Hidradenitis Supurativa , Masculino , Humanos , Femenino , Adolescente , Adulto , Anciano , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Absceso/tratamiento farmacológico , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Método Doble CiegoAsunto(s)
Alopecia Areata , Artritis Psoriásica , Hidradenitis Supurativa , Psoriasis , Humanos , Adalimumab/efectos adversos , Artritis Psoriásica/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Hidradenitis Supurativa/tratamiento farmacológico , Alopecia Areata/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamenteRESUMEN
Adalimumab is the only biological drug approved to date for the treatment of moderate and/or severe hidradenitis suppurativa. Adverse events reported during therapy include paradoxical psoriasiform reactions. No guidelines are currently available for the management of this clinical condition. The aim of this paper is to describe the incidence and clinical features of paradoxical psoriasiform eruptions occurring during treatment with adalimumab in patients with hidradenitis suppurativa and to report real-life experience in management and the possible role of other biologic agents for the treatment of both conditions.
Asunto(s)
Productos Biológicos , Hidradenitis Supurativa , Psoriasis , Humanos , Adalimumab , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inducido químicamente , Productos Biológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Factores Biológicos/uso terapéuticoRESUMEN
We report a clinical experience of treating concomitant atopic dermatitis and hidradenitis suppurativa (HS) with dupilumab. This report is particularly noticeable in terms of disease severity and treatment duration compared to previous reported cases, suggesting long-term dupilumab therapy can contribute to disease control even in patients with severe HS.