Impact of obesity on the efficacy of ustekinumab in Japanese patients with psoriasis: a retrospective cohort study of 111 patients

Yanaba, Koichi; Umezawa, Yoshinori; Ito, Toshihiro; Hayashi, Morito; Kikuchi, Sota; Fukuchi, Osamu; Saeki, Hidehisa; Nakagawa, Hidemi

doi:10.1007/s00403-014-1495-1

Cited by 23 publications

(21 citation statements)

References 23 publications

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“…S1; see Supporting Information). In the screening stage, we initially genotyped 18 common variants of 14 psoriasis susceptibility genes ( LCE3D , IL12B , NFKB1A , TNIP1 , ERAP1 , ZNF683 , MTHFR , AIM2 , PTTG1 , GJB2 , SYNE2 , IKZF3 , SERPINB8 , ZNF816A ) and HLA‐Cw6 status in 90 patients with psoriasis . All these variants had been significantly associated with psoriasis in populations of Han Chinese descent at a genome‐wide level ( P < 5 × 10 −8 ) and met the following quality criteria: (i) minor allele frequency higher than 5% in both cases and controls and (ii) Hardy–Weinberg equilibrium in cases and controls with P > 0·0001.…”

Section: Methodssupporting

confidence: 90%

“…Patients with higher BMI require a higher dosage and faster dose escalation than that used in our study. A previous study showed that patients with BMI ≥ 25 had a significantly lower percentage reduction in PASI than those with BMI < 25 at week 16 . The study by Umezawa et al .…”

Section: Discussionmentioning

confidence: 99%

“…also showed that BMI > 25 was associated with a higher proportion of insufficient responders than responders to ustekinumab. Other studies have determined that patients with psoriasis who have a high body weight or BMI had a lower chance of achieving a satisfactory outcome to treatment with MTX, ustekinumab and apremilast …”

Section: Discussionmentioning

confidence: 99%

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TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

et al. 2019

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Summary Background Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. Objectives To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. Methods A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single‐nucleotide polymorphisms in 14 susceptibility genes, and HLA‐Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. Results Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. Conclusions Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.

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Section: Methodssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

et al. 2019

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“…In addition to bringing overall cardiovascular and metabolic benefits, weight loss may increase the effectiveness of psoriasis treatments. For example, ustekinumab treatment was found to be less effective in patients with higher BMI . FPG remained stable in the overall population and showed a trend towards a decrease in the diabetic population.…”

Section: Discussionmentioning

confidence: 97%

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

Gerdes

Pinter

Papavassilis

et al. 2019

Acad Dermatol Venereol

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Background Psoriasis is associated with metabolic, liver and cardiovascular comorbidity. Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin‐17A, has shown significant and sustained efficacy in the treatment of moderate to severe psoriasis. Objectives This was an exploratory post hoc analysis of pooled data from three phase 3 studies in plaque psoriasis patient populations. The objective was to show the course of metabolic and liver parameters under secukinumab, etanercept or placebo treatment over time. A further objective was to assess the impact of selected comorbidities and metabolic characteristics on high‐sensitivity C‐reactive protein (hs‐CRP), as a surrogate marker of systemic inflammation. Methods Data from the phase 3 randomized controlled trials [FIXTURE (NCT01358578), ERASURE (NCT01365455) and SCULPTURE (NCT01406938); n = 3010] were included in this analysis. Patients were treated with secukinumab 150 mg or 300 mg, placebo or etanercept 50 mg (FIXTURE only) as active comparator. A set of metabolic and liver parameters was longitudinally assessed over 52 weeks. Multivariate regression analyses assessed the impact of selected comorbidities and metabolic characteristics on hs‐CRP levels at baseline and under treatment. Results Secukinumab treatment reduced hs‐CRP levels. Body weight and uric acid levels tended to decrease over 52 weeks with secukinumab. Secukinumab showed a neutral effect on fasting plasma glucose, lipid parameters and liver enzymes. Psoriatic arthritis, metabolic syndrome, obesity, impaired glucose metabolism, and hyperuricemia were each associated with increased hs‐CRP levels at baseline. Concomitant obesity attenuated the decline in hs‐CRP under treatment. Conclusions These analyses suggest neutral to favourable long‐term trends in metabolic and liver parameters under secukinumab treatment. Metabolic comorbidities were associated with increased hs‐CRP levels, reflecting the role of systemic inflammatory processes in their pathophysiology.

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“…However, only a few studies have focused on clinical factors that may predict the efficacy of ustekinumab on treatment outcomes. Previous studies have shown that high bodyweight, high BMI, longer disease duration, psoriatic arthritis (PsA) and prior use of biologic treatments are associated with lower rates of response to ustekinumab. In several studies evaluating the efficacy of biologics, poor response to biologic agents was most strongly associated with high BMI/bodyweight .…”

Section: Discussionmentioning

confidence: 99%

Clinical factors predicting the therapeutic response to ustekinumab in patients with moderate to severe chronic plaque psoriasis

Hwang

Youn

Kim

et al. 2016

The Journal of Dermatology

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While ustekinumab has been widely used as an effective biologic for the treatment of chronic plaque psoriasis, no prospective studies have specifically investigated the clinical factors that may influence treatment outcomes with ustekinumab. This post-hoc analysis aimed to identify specific clinical factors that may influence treatment outcomes with ustekinumab in psoriasis patients. In the MARCOPOLO study, 102 Korean patients with moderate to severe psoriasis were analyzed to assess the influence of baseline characteristics as clinical factors on clinical response (improvement in Psoriasis Area and Severity Index by ≥75%/90% [PASI75/PASI90]) to ustekinumab. In addition, differences in PASI75 and PASI90 responses between the responder group and non-responders were evaluated at weeks 28 and 52. Multiple logistic regression analysis was used to determine adjusted clinical factors predicting treatment outcomes among patient characteristics. At week 28, there was a significant difference in PASI75/PASI90 response based on prior biologic experience, although the difference did not persist at week 52. In addition, after adjusting for the effects of relevant clinical factors, biologic experience was significantly associated with less PASI75 (odds ratio [OR] = 0.14, P = 0.001) and PASI90 (OR = 0.22, P = 0.036) responses at week 28. The presence of comorbidities was higher among non-responders than among PASI75/PASI90 responders at both weeks 28 and 52, but was not statistically significant. Previous biologic use was the only clinical factor predicting less response at week 28, although it did not influence the clinical response after week 52. Further studies are warranted to investigate the association between presence of comorbidities and clinical response.

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Impact of obesity on the efficacy of ustekinumab in Japanese patients with psoriasis: a retrospective cohort study of 111 patients

Cited by 23 publications

References 23 publications

TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

TT genotype of rs10036748 in TNIP 1 shows better response to methotrexate in a Chinese population: a prospective cohort study

Effects of secukinumab on metabolic and liver parameters in plaque psoriasis patients

Clinical factors predicting the therapeutic response to ustekinumab in patients with moderate to severe chronic plaque psoriasis

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