Psoriasis pharmacogenetics: HLA-Cw*0602 as a marker of therapeutic response to ustekinumab

Raposo, Inês; Carvalho, Cláudia; Bettencourt, Andreia; Silva, Ana Martins; Leite, Luíz; Selores, Manuela; Torres, Tiago

doi:10.1684/ejd.2017.3071

European Journal of Dermatology

2017

DOI: 10.1684/ejd.2017.3071

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Psoriasis pharmacogenetics: HLA-Cw*0602 as a marker of therapeutic response to ustekinumab

Inês Raposo

Cláudia Carvalho

Andreia Bettencourt

et al.

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Cited by 16 publications

(40 citation statements)

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“…4 Second, this favourable response was confirmed Table 1 Baseline clinical characteristics for HLA-C*06:02 genotypes and HLA-C*06:02-POS subgroups Letters to the Editor e365 by a significant improvement in drug survival, corroborating studies supporting the use of ustekinumab over other biologics in HLA-C*06-POS patients. 4,5,8 Third, we identified a subgroup of HLA-C*06:02 patients, carrier also for the HLA-C*04 allele, as a 'super responder' subgroup, where complete remission was observed in >70% of patients up to 2 years. The underlying mechanisms by which ustekinumab affords benefit in patients carrying the HLA-C*06 are not fully understood; however, potential mechanisms have been described.…”

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confidence: 88%

See 1 more Smart Citation

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Cesare

Bianchi

Pescitelli

et al. 2019

Acad Dermatol Venereol

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P < 0.0001), higher number of comorbidities (P < 0.0001) and a younger onset of psoriasis (P = 0.0002). In the biologic-treated population, females were significantly affected with PsA (P = 0.00159), while male patients had higher BMI (P = 0.0083), more severe PASI at baseline (P = 0.0022), and had more frequently concurrent chronic/latent infection (0.0074). Interestingly, our results showed that female sex was more frequently affected by AIE (P = 0.0077), independently from disease severity, concomitant PsA, BMI, concurrent chronic/latent infections and comorbidities. However, the frequency of AIE was similar to females in males with smoking habits (P = 0.7456), suggesting that smoking might be a risk factor for males. Moreover, males with AIE had a younger onset of psoriasis compared to female sex with and without AIE and males without AIE (P = 0.0408).Additionally, our results showed that AIE are observed in long-term treated patients (P = 0.0815). Although no association between AIE and a specific biologic was observed, we found differences in the timing of presentation of AIE between biologic classes. Actually, patients treated with anti-IL12/23-Th17 pathway biologics usually reported AIE in the first months of treatment. Conversely, long-term exposure to anti-TNFa might increase observation of AIE (P = 0.0179). When we looked at patients (34/167 patients, 27/34 patients treated with anti-TNFa, 7/34 patients treated with anti-IL-23/23-Th17 pathway) who started the actual biologic between six months and one year from the moment of our observation, we found that AIE had an early presentation in 7/34 patients with only 2/7 patients on anti-TNFa (P = 0.0014). This is an interesting observation that could be linked to the different mechanisms of action and the different dosing schedule among all the biologics; however, given the small numbers of patients, our data need to be confirmed.Concomitant chronic latent HBV and HCV infections were not considered a limitation for biologics prescription. 9,10 In our study, these conditions did not influence the occurrence of AIE, occurring more frequently in the male sex that displayed fewer AIE. Following standard protocols, no tubercular reactivations were reported.In conclusion, we believe that factors such as sex, smoking, earlier onset of psoriasis, total comorbidities and overall biologic treatment duration are relevant in the management of moderate-to-severe psoriasis, besides the class of biologic agents. It should be advisable to consider vaccination for varicella-zoster virus, HBV, influenza virus, Hib virus and HPV in patients with psoriasis. Figure 1 Psoriasis area and severity index (PASI) 75, 90, 100 response and retention rate in subgroups of HLA-C*06:02-POS patients in response to ustekinumab treatment over 2 years. Proportion of patients achieving PASI 75 (a), PASI 90 (b) or PASI 100 (c). Cumulative probability of drug survival in HLA-C

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confidence: 88%

“…2,4 Encouraging results on the chances of achieving lasting responses after the treatment have been reported in patients on brentuximab vedotin. 5 However, only a small cohort of patients have been enrolled in clinical trials 5 ; thus, no definitive conclusions can be drawn.…”

mentioning

confidence: 99%

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Cesare

Bianchi

Pescitelli

et al. 2019

Acad Dermatol Venereol

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“…[5][6][7][8][9][10][11] The relationship of HLA alleles to a refractory course has been studied in other autoimmune disorders, including rheumatoid arthritis and psoriasis. 12,13 HLA alleles have also been found to be related to disease severity and progression in rheumatoid arthritis 12,14,15 and in multiple sclerosis. 16,17 Identifying the characteristics of refractory patients is important to the design of optimal treatment approaches, including the development of therapies that are effective in this subgroup.…”

mentioning

confidence: 99%

“…The association of MG with human leukocyte antigens (HLA) has been described in different populations . The relationship of HLA alleles to a refractory course has been studied in other autoimmune disorders, including rheumatoid arthritis and psoriasis . HLA alleles have also been found to be related to disease severity and progression in rheumatoid arthritis and in multiple sclerosis …”

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confidence: 99%

Refractory myasthenia gravis: Characteristics of a portuguese cohort

et al. 2019

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Introduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments. Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA‐DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Results: Twenty‐two patients were found to have RMG (19.3%). There were no differences between non‐RMG and RMG patients with respect to sex, age of onset, abnormal 3‐Hz repetitive nerve stimulation, anti‐acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA‐DRB1*03 was more frequent in the non‐RMG vs. control population (P = 3 × 10−6). The HLA‐DRB1*13 allele was less frequent in non‐RMG patients compared with controls (P = 0.002), and less frequent in the non‐RMG group compared with the RMG group (P = 0.003). Discussion: HLA‐DRB1*03 was more common in non‐RMG, and the HLA‐DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188–191, 2019

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“…Psoriatic patients carrying the HLA-C*06:02 allele have improved response to ustekinumab compared to those without, [4][5][6] and aside from HLA-C*06:02, psoriasis is associated with HLA-C*12:03, HLA-C*07:01, HLA-C*07:02 and HLA-C*07:04. 7 Here, we have used high-resolution HLA typing to evaluate the role of HLA-C antigen variants on effectiveness and drug survival of ustekinumab in patients with moderate-severe psoriasis over 2 years.…”

mentioning

confidence: 99%

High‐resolution HLA typing identifies a new ‘super responder’ subgroup of HLA‐C06:02‐positive psoriatic patients: HLA‐C06:02/HLA‐C*04, in response to ustekinumab

Talamonti

D’Adamio

Galluccio

et al. 2019

Acad Dermatol Venereol

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In the biologic-treated population, females were significantly affected with PsA (P = 0.00159), while male patients had higher BMI (P = 0.0083), more severe PASI at baseline (P = 0.0022), and had more frequently concurrent chronic/latent infection (0.0074). Interestingly, our results showed that female sex was more frequently affected by AIE (P = 0.0077), independently from disease severity, concomitant PsA, BMI, concurrent chronic/latent infections and comorbidities. However, the frequency of AIE was similar to females in males with smoking habits (P = 0.7456), suggesting that smoking might be a risk factor for males. Moreover, males with AIE had a younger onset of psoriasis compared to female sex with and without AIE and males without AIE (P = 0.0408). Additionally, our results showed that AIE are observed in long-term treated patients (P = 0.0815). Although no association between AIE and a specific biologic was observed, we found differences in the timing of presentation of AIE between biologic classes. Actually, patients treated with anti-IL12/23-Th17 pathway biologics usually reported AIE in the first months of treatment. Conversely, long-term exposure to anti-TNFa might increase observation of AIE (P = 0.0179). When we looked at patients (34/167 patients, 27/34 patients treated with anti-TNFa, 7/34 patients treated with anti-IL-23/23-Th17 pathway) who started the actual biologic between six months and one year from the moment of our observation, we found that AIE had an early presentation in 7/34 patients with only 2/7 patients on anti-TNFa (P = 0.0014). This is an interesting observation that could be linked to the different mechanisms of action and the different dosing schedule among all the biologics; however, given the small numbers of patients, our data need to be confirmed. Concomitant chronic latent HBV and HCV infections were not considered a limitation for biologics prescription. 9,10 In our study, these conditions did not influence the occurrence of AIE, occurring more frequently in the male sex that displayed fewer AIE. Following standard protocols, no tubercular reactivations were reported. In conclusion, we believe that factors such as sex, smoking, earlier onset of psoriasis, total comorbidities and overall biologic treatment duration are relevant in the management of moderate-to-severe psoriasis, besides the class of biologic agents. It should be advisable to consider vaccination for varicella-zoster virus, HBV, influenza virus, Hib virus and HPV in patients with psoriasis.

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Psoriasis pharmacogenetics: HLA-Cw*0602 as a marker of therapeutic response to ustekinumab

Cited by 16 publications

References 10 publications

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Refractory myasthenia gravis: Characteristics of a portuguese cohort

High‐resolution HLA typing identifies a new ‘super responder’ subgroup of HLA‐C06:02‐positive psoriatic patients: HLA‐C06:02/HLA‐C*04, in response to ustekinumab

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Psoriasis pharmacogenetics: HLA-Cw*0602 as a marker of therapeutic response to ustekinumab

Cited by 16 publications

References 10 publications

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Risk of acute infections in psoriatic patients during biologic therapies is linked to gender

Refractory myasthenia gravis: Characteristics of a portuguese cohort

High‐resolution HLA typing identifies a new ‘super responder’ subgroup of HLA‐C*06:02‐positive psoriatic patients: HLA‐C*06:02/HLA‐C*04, in response to ustekinumab

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High‐resolution HLA typing identifies a new ‘super responder’ subgroup of HLA‐C06:02‐positive psoriatic patients: HLA‐C06:02/HLA‐C*04, in response to ustekinumab