1. Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis
Kyriakou, A. Patsatsi, D. Sotiriadis, D.G. Goulis
Medical School, Aristotle University of Thessaloniki, Greece
British Journal of Dermatology. DOI: /bjd.16437

2. Aikaterini Kyriakou, Lead author

3. Introduction What’s already known?
Adipokines are suggested to represent the pathophysiologic link between psoriatic lesions and metabolic alterations.
Results regarding the effects of treatment on circulating adipokines in psoriatic patients are inconsistent.

4. Objective
To systematically review the literature for studies that investigated possible differences in the circulating levels of leptin, adiponectin or resistin in psoriatic patients before and after any treatment intervention and meta-analyze the best evidence available.

5. Methods (1)
Study selection. Eligible for the systematic review and meta-analysis were studies that have assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment intervention.

6. Methods (2)
Search strategy. To identify eligible studies, the main search was conducted in three electronic databases, namely PubMed, Cochrane Library and Embase (last search was conducted on November 13th, 2017).

7. Methods (3)
Data extraction. Data extraction was performed independently by two researchers (AK, AP). Any disagreement between the researchers responsible for the initial data extraction was solved by unanimous consensus, involving a third researcher (DGG), not contributed in the initial procedure.

8. Methods (4)
Outcome measures. The main outcome measure was difference in plasma/serum concentrations of leptin, resistin or adiponectin before and after treatment for psoriasis.
Quality assessment. In order to assess the quality of the included studies, the RTI Item Bank Tool for observational studies was used

9. Results (1)
Leptin:
After treatment, blood concentrations of leptin were similar to the relevant ones before treatment (random effect model, SMD: 0.06, 95% CI: to 0.20), with no heterogeneity among studies (I2: 0%, p = 0.875).

10. Results (2)
Leptin:
None of the corrections according to numeric modifiers (meta-regression, test of moderators: p = for BMI before treatment; p = for PASI before treatment; p = for RTI score) or categorical modifiers (stratified analysis for treatment method and follow-up duration) showed a significant effect. No significant publication bias was detected among studies (Egger test, p = 0.131).

11. Results (3) Adiponectin:
After treatment, blood concentrations of adiponectin were similar to the relevant ones before treatment (random effect model, SMD: -0.14, 95% CI: to 0.05), with significant heterogeneity among studies (I2: 36.8%, p = 0.032).
None of the corrections according to numeric modifiers (meta-regression, test of moderators: p = for BMI before treatment; p = for PASI before treatment; p = for RTI score) showed a significant effect.

12. Results (4) Adiponectin:
Studies that achieved > 75% difference in PASI resulted in an increase in adiponectin concentrations after treatment (SMD: -0.77, 95% CI: to -0.25) as well as studies with duration of weeks (SMD: , 95% CI: to -0.01).
Significant publication bias was detected (Egger test, p = 0.007).

13. Results (5)
Resistin:
After treatment, blood concentrations of resistin were significantly lower as compared to the relevant ones before treatment (SMD: 0.50, 95% CI: 0.20 to 0.79), with significant heterogeneity among studies (I2: 61.4%, p < 0.001).

14. Results (6)
Resistin:
None of the corrections according to numeric modifiers (meta-regression, test of moderators: p = for BMI before treatment; p = for PASI before treatment; p = for RTI score) showed a significant effect.
Significant publication bias was detected (Egger test, p < 0.001).

15. Results (7)
Resistin:
Categorical modifiers showed that the reduction in resistin concentrations remained significant only for the “Adalimumab, Etanercept, Infliximab, Ustekinumab” treatment option (stratified analysis for treatment method and the “> 75%” category in PASI difference (stratified analysis for ΔPASI) as well as studies with duration of weeks (SMD: 1.00, 95% CI: 0.19 to 1.81) and > 24 weeks (SMD: 0.98, 95% CI: 0.48 to 1.48) (stratified analysis for treatment duration).

16. Discussion (1)
There is no evidence that any type of treatment for psoriasis modifies leptin and adiponectin concentrations.
On the other hand, treatment intervention reduces resistin concentrations (especially, treatment with biologicals and where a reduction in PASI of > 75% is achieved).

17. Discussion (2)
This change in resistin concentrations (SMD 0.50, 95% CI: 0.20 to 0.79) is expected to be of clinical importance as the effect is on the same magnitude reported between hypertensive and normotensive populations (SMD 0.85, 95% CI 0.15 to 1.54) 43, as well as between hyperglycemic and euglycemic populations (mean difference 1.1 ± 1.3 ng/dl).

18. Discussion (3)
This review has showed that drugs for psoriasis treatment do not modify adipokine concentrations and have no adverse metabolic consequences. However, many of the studies measured adipokines at different time-points.

19. Discussion (4)
The lack of effect of therapy on adiponectin and leptin and the small effect on resistin may reflect that adipokine levels do not change after treatment intervention; but it is possible that the levels do not change for some certain time period after therapy.

20. Discussion (5)
It is probable that the abnormalities in adipokines are due to adiposity and therefore may not change unless the BMI decreases

21. Discussion (6)
As a consequence, it remains the responsibility of dermatologists to counsel patients with psoriasis for the increased risk of cardiovascular disease.

22. Discussion (7)
The need for lifestyle modifications and the necessity for annual screening regarding metabolic syndrome and cardiovascular risk factors in patients with psoriasis is mandatory and these should be managed according to guidelines.

23. Conclusions
There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations; however, it reduces resistin concentrations.
The absolute reduction in resistin concentrations is expected to be of clinical importance.

24. Acknowledgments to our colleagues

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