RESUMO
BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.
Assuntos
Produtos Biológicos , Psoríase , Adalimumab , Áustria , Estudos de Coortes , Etanercepte , Feminino , Humanos , Psoríase/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , UstekinumabRESUMO
The exact mechanisms of photohardening in polymorphic light eruption (PLE) are still unknown, but medical photohardening was shown to increase regulatory T cell (Treg) numbers in the blood of PLE patients, similar to natural hardening. Furthermore, oral vitamin D supplementation increased peripheral Tregs in healthy individuals. We herein report on a post hoc analysis of 26 screened PLE patients of a clinical trial (ClinicalTrials.gov No. NCT01595893), in which the influence of the progressing season was investigated on baseline CD4+CD25+FoxP3+CD127- Treg numbers by flow cytometry and Treg suppressive function by co-culture assays with T effector cells as a secondary endpoint, together with 25-hydroxy vitamin D (25(OH)D) serum levels at the study's screening visit, taking place in the period from January to June. The mean 25(OH)D serum level of all patients was 33.2 ng ml(-1). Ten of those patients (38.5%) were identified with low 25(OH)D levels (<30 ng ml(-1)). Significantly higher baseline 25(OH)D serum levels (plus 34.4%; P = 0.0182) as well as higher relative Treg percentages in CD4+ population (plus 62.8%; P = 0.0157) and in total lymphocyte population (plus 59.6%; P = 0.0372) and higher absolute Treg numbers (plus 100.2%; P = 0.0042) were observed in the late spring/early summer period (April to June) compared to the winter period (January to February). No significant relationship was observed when Treg numbers and function were correlated with 25(OH)D levels. These data indicate that in PLE patients Treg numbers and their suppressive function are independent of vitamin D serum levels and suggest that UV light and/or other seasonal factors may affect these cells via the non-vitamin D related pathway(s).
Assuntos
Dermatite de Contato/sangue , Dermatite de Contato/imunologia , Estações do Ano , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos da radiação , Raios Ultravioleta , Vitamina D/sangue , Adulto , Idoso , Dermatite de Contato/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/citologia , Adulto JovemRESUMO
BACKGROUND: We hypothesized that regulatory T cells (Tregs) are involved in the immunological abnormalities seen in patients with polymorphic light eruption (PLE). OBJECTIVES: To investigate the number and suppressive function of peripheral Tregs in patients with PLE compared with healthy controls. METHODS: Blood sampling was done in 30 patients with PLE [seeking or not seeking 311-nm ultraviolet (UV)B photohardening] as well as 19 healthy controls at two time points: TP1, March to June (before phototherapy); and TP2, May to August (after phototherapy). We compared the number of CD4(+) CD25(high) CD127(-) FoxP3(+) Tregs by flow cytometry and their function by assessing FoxP3 mRNA levels and effector T cell/Treg suppression assays. RESULTS: Tregs isolated from healthy controls significantly suppressed the proliferation of effector T cells at TP1 by 68% (P = 0·0156). In contrast, Tregs from patients with PLE entirely lacked the capacity to suppress effector T-cell proliferation at that time point. The medical photohardening seen in 23 patients with PLE resulted in a significant increase in the median percentage of circulating Tregs [both as a proportion of all lymphocytes; 65 6% increase (P = 0·0049), and as a proportion of CD4(+) T cells; 32.5% increase (P = 0·0049)]. This was accompanied by an increase in the expression of FoxP3 mRNA (P = 0·0083) and relative immunosuppressive function of Tregs (P = 0·083) comparing the two time points in representative subsets of patients with healthy controls tested. Seven patients with PLE not receiving 311-nm UVB also exhibited an increase in the number of Tregs but this was not statistically significant. No significant differences in Treg numbers were observed in healthy subjects between the two time points. CONCLUSIONS: An impaired Treg function is likely to play a role in PLE pathogenesis. A UV-induced increase in the number of Tregs (either naturally or therapeutically) may be a compensatory mechanism by which the immune system counteracts the susceptibility to PLE.
Assuntos
Transtornos de Fotossensibilidade/imunologia , Linfócitos T Reguladores/fisiologia , Terapia Ultravioleta/métodos , Adolescente , Adulto , Idoso , Proliferação de Células/fisiologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/metabolismo , Transtornos de Fotossensibilidade/radioterapia , Estações do Ano , Linfócitos T Reguladores/metabolismo , Regulação para Cima/fisiologia , Adulto JovemAssuntos
Interleucinas/metabolismo , Transtornos de Fotossensibilidade/imunologia , Pele/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CD11b/metabolismo , Estudos de Casos e Controles , Criança , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/patologia , Psoríase/imunologia , Psoríase/patologia , Pele/citologia , Pele/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
BACKGROUND: Treatment with the interleukin-12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque-type psoriasis. OBJECTIVES: To determine whether concomitant 311-nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. METHODS: Ten patients (five women and five men; mean age 58years, range 48-66) with moderate to severe plaque-type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90mg subcutaneously depending on body weight (below or above 100kg) at weeks 0 and 4. Within 2days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311-nm UVB-based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6weeks. Treatment response was monitored weekly in terms of half-body PASI. RESULTS: Nine patients completed the study. Analysis of their data showed that 311-nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311-nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3-5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV-irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P=0·007). At week 12, this synergistic effect of 311-nm UVB was still apparent although not significantly so. CONCLUSIONS: Treatment with 311-nm UVB accelerates the clearance of psoriatic lesions in ustekinumab-treated patients.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/radioterapia , Terapia Ultravioleta/métodos , Administração Cutânea , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Terapia Combinada , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Resultado do Tratamento , Terapia Ultravioleta/efeitos adversos , UstekinumabRESUMO
BACKGROUND: Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. OBJECTIVES: To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. METHODS: Data from a psoriasis registry (http://www.psoriasis-therapieregister.at) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5-methoxypsoralen (5-MOP; n = 32) and 8-methoxypsoralen (8-MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8-MOP and 5-MOP, respectively) and at week 12 for biologics. RESULTS: Intention-to-treat-as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post-hoc modified worst-case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. CONCLUSIONS: Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head-to-head studies of PUVA and biologics are warranted to confirm these observations.
Assuntos
Produtos Biológicos/uso terapêutico , Terapia PUVA/métodos , Psoríase/tratamento farmacológico , 5-Metoxipsoraleno , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Doença Crônica , Terapia Combinada/métodos , Feminino , Humanos , Masculino , Metoxaleno/análogos & derivados , Metoxaleno/uso terapêutico , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Polymorphic light eruption (PLE) is a very frequent photodermatosis whose pathogenesis may involve resistance to ultraviolet (UV)-induced immune suppression. Similar to UV radiation, calcitriol (1,25-dihydroxyvitamin D3) and its analogues such as calcipotriol have been shown to exhibit immunosuppressive properties. OBJECTIVES: We performed a randomized double-blinded placebo-controlled intraindividual half-body trial (NCT00871052) to investigate the preventive effect of a calcipotriol-containing cream in PLE. METHODS: Thirteen patients with PLE (10 women, three men; mean age 37 years) pretreated their skin on two symmetrically located test fields with calcipotriol or placebo cream twice daily for 7 days before the start of photoprovocation testing with solar-simulated UV radiation. We established a specific PLE test score [AA + SI + 0·4 P (range 0-12), where AA is affected area score (range 0-4), SI is skin infiltration score (range 0-4) and P is pruritus score on a visual analogue scale (range 0-10)] to quantify PLE severity. RESULTS: Photoprovocation led to PLE lesions in 12/13 (92%) patients. As shown by the PLE test score, compared with placebo calcipotrial pretreatment significantly reduced PLE symptoms in average by 32% (95% confidence interval 21-44%; P = 0·0022, exact Wilcoxon signed-rank test) throughout the observation period starting at 48 h until 144 h after the first photoprovocation exposure. At 48, 72 and 144 h calcipotriol pretreatment resulted in a lower PLE test score in 7 (58%), 9 (75%) and 10 (83%) of the 12 cases, respectively. Considering all time points together, calcipotriol diminished the PLE test score in all 12 photoprovocable patients (P = 0·0005; Wilcoxon signed-rank test). CONCLUSIONS: These results suggest a potential therapeutic benefit of topical 1,25-dihydroxyvitamin D3 analogues as prophylactic treatment in patients with PLE.