Does Weight Loss Reduce the Severity and Incidence of Psoriasis or Psoriatic Arthritis?

A Critically Appraised Topic

S.K. Mahil; S.M. McSweeney; E. Kloczko; B. McGowan; J.N. Barker; C.H. Smith

The British Journal of Dermatology. 2019;181(5):946-953.

Abstract and Introduction

Abstract

Clinical question: Does weight loss reduce the severity and incidence of psoriasis or psoriatic arthritis (PsA) in obese individuals?

Background: Obesity presents a rising public health challenge and is more prevalent among individuals with psoriasis or PsA than in the general population. Longitudinal population-based studies suggest a causal role for obesity in psoriasis and PsA onset and that obesity drives greater disease severity.

Methods: We systematically reviewed evidence within the MEDLINE, Embase and CENTRAL databases and clinical trials registries examining lifestyle, pharmacological and surgical weight loss interventions in the treatment and prevention of psoriasis and PsA in obese individuals. Meta-analysis was conducted using random-effects models, followed by sensitivity analyses.

Results: Of 176 full-text articles reviewed, 14 met the inclusion criteria. Meta-analysis of six randomized control trials (RCTs) confirmed that weight loss following lifestyle interventions (diet or physical activity) improves psoriasis compared with control [mean change in Psoriasis Area and Severity Index −2·59, 95% confidence interval (CI) −4·09 to −1·09; P < 0·001]. One RCT demonstrated a greater likelihood of achieving minimal PsA activity following diet-induced weight loss (odds ratio 4·20, 95% CI 1·82–9·66; P < 0·001). Three studies of pharmacological treatments reported conflicting results, and no RCTs of bariatric surgery were identified. Two cohort studies suggested that bariatric surgery, particularly gastric bypass, reduces the risk of developing psoriasis (hazard ratio 0·52, 95% CI 0·33–0·81; P < 0·01).

Conclusions: These limited data indicate that weight loss can improve pre-existing psoriasis and PsA, and prevent the onset of psoriasis in obese individuals. Together with the National Institute for Health and Care Excellence obesity guidance, this informed a local obesity screening and management pathway, providing multidisciplinary weight loss interventions alongside conventional skin-focused care for patients with psoriasis.

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Next Section

Abstract and Introduction
Clinical Scenario
Clinical Question
Background
Methods
Results
Discussion
Clinical Implications
What did we do in Light of the Evidence?
Clinical Message
References

Table S1. Search strategy and results.
Database	Search Strategy	Date	Hits
PubMed	(("Psoriasis"[Mesh] OR psoriasis) OR ("Arthritis, Psoriatic"[Mesh] OR psoriatic arthritis)) AND ("Weight Loss"[Mesh] OR weight loss OR "Anti-Obesity Agents"[Mesh] OR anti-obesity agents OR "orlistat"[Supplementary Concept] OR orlistat OR tetrahydrolipstatin OR empagliflozin OR "empagliflozin" [Supplementary Concept] OR "liraglutide"[MeSH Terms] OR liraglutide OR "exenatide"[Supplementary Concept] OR exenatide OR exendin OR "lixisenatide"[Supplementary Concept] OR lixisenatide OR "dulaglutide"[Supplementary Concept] OR dulaglutide OR "Weight Reduction Programs"[Mesh] OR weight reduction programs OR "Diet, Reducing"[Mesh] OR reducing diet)	07/09/2018	206
PubMed	(("Psoriasis"[Mesh] OR psoriasis) OR ("Arthritis, Psoriatic"[Mesh] OR psoriatic arthritis)) AND ("Obesity"[Mesh] OR obesity OR "Pediatric Obesity"[Mesh] OR pediatric obesity OR "Obesity, Abdominal"[Mesh] OR abdominal obesity OR "Obesity, Morbid"[Mesh] OR morbid obesity OR "Obesity, Metabolically Benign"[Mesh] OR metabolically benign obesity OR "Abdominal obesity metabolic syndrome"[Supplementary Concept] OR abdominal obesity metabolic syndrome)	07/09/2018	815
CENTRAL	#1 MeSH descriptor: [Psoriasis] explode all trees #2 psoriasis #3 MeSH descriptor: [Arthritis, Psoriatic] explode all trees #4 psoriatic arthritis #5 MeSH descriptor: [Weight Loss] explode all trees #6 weight loss #7 MeSH descriptor: [Anti-Obesity Agents] explode all trees #8 anti-obesity agents #9 orlistat #10 tetrahydrolipstatin #11 MeSH descriptor: [Liraglutide] explode all trees #12 liraglutide #13 exenatide #14 exendin #15 lixisenatide #16 dulaglutide #17 MeSH descriptor: [Weight Reduction Programs] explode all trees #18 weight reduction programs #19 MeSH descriptor: [Diet, Reducing] explode all trees #20 reducing diet #21 (#1 OR #2 OR #3 OR #4) AND (#5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20)	07/09/2018	89
CENTRAL	#1 MeSH descriptor: [Psoriasis] explode all trees #2 psoriasis #3 MeSH descriptor: [Arthritis, Psoriatic] explode all trees #4 psoriatic arthritis #22 MeSH descriptor: [Obesity] explode all trees #23 obesity #24 MeSH descriptor: [Pediatric Obesity] explode all trees #25 pediatric obesity #26 MeSH descriptor: [Obesity, Abdominal] explode all trees #27 abdominal obesity #28 MeSH descriptor: [Obesity, Morbid] explode all trees #29 morbid obesity #30 MeSH descriptor: [Obesity, Metabolically Benign] explode all trees #31 metabolically benign obesity #32 Abdominal obesity metabolic syndrome #33 (#1 OR #2 OR #3 OR #4) AND (#22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32)	07/09/2018	93
EMBASE	1. exp nail psoriasis/or exp psoriasis vulgaris/or psoriasis.mp. or exp psoriasis/or exp scalp psoriasis/or exp erythrodermic psoriasis/ 2. psoriatic arthritis.mp. or exp psoriatic arthritis/ 3. weight loss.mp. or exp body weight loss/ 4. anti-obesity agents.mp. or exp antiobesity agent/ 5. orlistat.mp. or exp tetrahydrolipstatin/ 6. empagliflozin.mp. or exp empagliflozin/ 7. exp liraglutide/or liraglutide.mp. 8. exenatide.mp. or exp exendin 4/ 9. exp lixisenatide/or lixisenatide.mp. 10. dulaglutide.mp. or exp dulaglutide/ 11. weight reduction program.mp. or exp weight loss program/ 12. reducing diet.mp. or exp low calory diet/ 13. 1 or 2 14. 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 15. 13 and 14	07/09/2018	466
EMBASE	1. exp psoriasis vulgaris/or psoriasis.mp. or exp nail psoriasis/or exp erythrodermic psoriasis/or exp scalp psoriasis/or exp psoriasis/ 2. psoriatic arthritis.mp. or exp psoriatic arthritis/ 3. exp maternal obesity/or exp obesity management/or exp diabetic obesity/or exp metabolically benign obesity/or exp obesity/or exp childhood obesity/or exp sarcopenic obesity/or exp morbid obesity/or exp adolescent obesity/or exp diet induced obesity/or exp abdominal obesity/or obesity.mp. 4. pediatric obesity.mp. or exp childhood obesity/ 5. abdominal obesity.mp. or exp obesity/or exp abdominal obesity/ 6. morbid obesity.mp. or exp morbid obesity/ 7. metabolically benign obesity.mp. or exp obesity/or exp metabolically benign obesity/or exp metabolic syndrome X/ 8. exp metabolic syndrome X/or exp obesity/or exp abdominal obesity/or abdominal obesity metabolic syndrome.mp. 9. 1 or 2 10. 3 or 4 or 5 or 6 or 7 or 8 11. 9 and 10	07/09/2018	2836
EU trials registry	Psoriasis weight loss	07/09/2018	4
EU trials registry	Psoriasis obesity	07/09/2018	0
EU trials registry	Psoriatic arthritis weight loss	07/09/2018	0
EU trials registry	Psoriatic arthritis obesity	07/09/2018	0
Clinicaltrials.gov	Psoriasis AND weight loss	07/09/2018	14
Clinicaltrials.gov	Psoriasis AND obesity	07/09/2018	36
Clinicaltrials.gov	Psoriatic arthritis AND weight loss	07/09/2018	4
Clinicaltrials.gov	Psoriatic arthritis AND obesity	07/09/2018	6
WHO trials registry	Psoriasis weight loss	07/09/2018	2
WHO trials registry	Psoriasis obesity	07/09/2018	5
WHO trials registry	Psoriatic arthritis weight loss	07/09/2018	0
WHO trials registry	Psoriatic arthritis obesity	07/09/2018	0
Secondary Searching	-	07/09/2018	0

NOTE: Search strings are displayed as they were used in each database or registry. Date represents the day on which the final search was performed.

Table S2. Sensitivity analyses performed as part of meta-analysis.
Parameter	Effect	Conclusion
Included Studies
Exclusion of an individual study.	Risk ratio – PASI75 No studies excluded: 1.47 (1.26, 1.72) Al-Mutairi et al: 1.52 (1.09, 2.11) Gisondi et al: 1.41 (1.20, 1.65) Kimball et al: 1.47 (1.26, 1.72) Naldi et al: 1.53 (1.31, 1.79) Change in PASI No studies excluded: -2.59 (-4.09, -1.09) Gisondi et al: -2.37 (-4.31, -0.42) Guida et al: -2.03 (-3.42, -0.65) Jensen et al: -2.76 (-4.68, -0.84) Naldi et al: -3.29 (-4.38, -2.20)	Exclusion of individual studies did not affect the direction of treatment effect but had some effect on the size of treatment effect.
Exclusion of studies at high risk of bias.	Risk ratio – PASI75 All studies included: 1.47 (1.26, 1.72) Studies at high RoB excluded: 1.65 (0.94, 2.91) Change in PASI All studies included: -2.59 (-4.09, -1.09) Studies at high RoB excluded: -2.03 (-3.42, -0.65)
Analysis Methods
Reported outcome measure (risk ratio vs. odds ratio vs. risk difference) for proportion achieving PASI75	Risk ratio: 1.47 (1.27, 1.69) Odds ratio: 2.75 (1.32, 5.74) Risk difference: 0.21 (0.05, 0.37)	Using different reported outcome measures did not change the direction of treatment effect but did affect the estimate of the size of treatment effect.
Fixed effects vs. random effects method	Proportion achieving PASI75 Fixed effects: 1.47 (1.26, 1.72) Random effects: 1.47 (1.27, 1.69) Change in PASI Fixed effects: -2.45 (-3.13, -1.77) Random effects: -2.59 (-4.09, -1.09)	Minimal effect on direction and size of outcome measure.
Imputed Data
Including studies with imputed data vs. including studies without imputed data only	Imputed data: -2.59 (-4.09, -1.09) No imputed data: -1.30 (-2.24, -0.37)	The use of imputed data did not change the direction of treatment effect but did change the size of the estimated treatment effect.

PASI, psoriasis area and severity index; RoB, risk of bias.

Table S3. Summary of studies.
Study	Design	Age	BMI	Baseline Disease Activity	Intervention	Comparator	Duration	Mean %Weight Change	Outcome		Comment
Lifestyle (Diet/Physical Activity) Weight Loss Interventions in Psoriasis
Gisondi et al (27)	RCT (n=61)	51.6±12.5 years	33.7±4.3 kg/m²	PASI: 14.6±5.9	2.5mg/kg/day ciclosporin and supervised low calorie diet	2.5mg/kg/day ciclosporin only	24 weeks	Intervention: -7.0% Control: -0.2%	%PASI75 Intervention: 66.7% Control: 29.0%	p<0.001	Weight loss (5–10%) improves response to ciclosporin in moderate/severe psoriasis
Al-Mutairi et al (28)	RCT (n=262)	46.0±6.5 years	29.4±4.7 kg/m²	PASI: 31.9±6.0	Supervised low calorie diet	No specific diet advised	24 weeks	Intervention: -13.0% Control: -1.5%	%PASI75 Intervention: 85.9% Control: 59.3%	p<0.001	Weight loss (>10%) improves moderate/severe psoriasis
Guida et al (29)	RCT (n=44)	52.0±10.9 years	32.2±3.2 kg/m²	PASI: 8.3±3.8	Supervised low calorie diet, high n-3 PUFAs and low n-6 PUFAs	No specific diet advised	24 weeks	Intervention: -11.4% Control: +2.1%	ΔPASI Intervention: -5.1±1.8 Control: -1.1±2.4	p=0.021	Weight loss (>10%) improves mild psoriasis
Naldi et al (30)	RCT (n=303)	53.0±14.1 years	30.8±4.6 kg/m²	PASI: 4.0±7.9	Supervised low calorie diet and personalised exercise plan	Counselling re: benefits of weight loss in psoriasis	20 weeks	Intervention: -3.0% Control: -1.8%	%PASI75 Intervention: 24.5% Control: 19.1%	p=0.25	Weight loss <5%. No improvement in mild psoriasis.
Jensen et al (31)	RCT (n=60)	50.8±10.3 years	34.2±5.2 kg/m²	PASI: 5.4±2.8	Supervised low calorie diet	Supervised healthy diet	16 weeks	Intervention: -14.8% Control: -0.4%	ΔPASI Intervention: -2.3±3.8 Control: -0.3±3.8	p=0.06	Trend towards weight loss (>10%) improving mild psoriasis
Kimball et al (32)	RCT (n=30)	47.2±13.8 years	104.2 kg^a	PASI: 15.4±6.1	Narrowband UVB therapy and supervised low calorie diet (Ornish or South Beach)	Narrowband UVB only	12 weeks	Ornish diet: -8.0% South Beach diet: -7.0% Control: 0%	%PASI75 Ornish diet: 83.0% South Beach diet: 56.0% Control: 38.0%	p=0.3	Weight loss (5–10%) does not improve response to narrowband UVB in moderate/severe psoriasis
Del Giglio et al (33)	RCT (n=42)	59.6±9.7 years	31.4±1.7 kg/m²	PASI: 1.0±1.1	Methotrexate until PASI75 for 12 weeks, then stopped and supervised low calorie diet started	Methotrexate therapy until PASI75 for 12 weeks, then stopped and no specific diet advised	24 weeks	Intervention: -9.0% Control: 0%	PASI Intervention: PASI worsened over time Control: PASI worsened over time	p>0.05	Weight loss (5–10%) cannot maintain moderate/severe psoriasis remission after methotrexate is stopped
Jensen et al (34)	Cohort study as follow-up to Jensen et al (31) (n=56)	51.1±9.9 years	34.4±5.3 kg/m²	PASI: 4.8±3.0	Supervised low calorie diet (16 weeks), then maintenance diet	-	64 weeks	After low calorie diet: -14.1% After maintenance diet: -9.5%	ΔPASI After low calorie diet: -2.3±3.1 After maintenance diet: -2.9±3.8	p<0.05 p<0.05	Improvement in mild psoriasis from weight loss can be maintained up to 64 weeks
Lifestyle (Diet/Physical Activity) Weight Loss Interventions in PsA
Di Minno et al (35)	RCT (n=126)	45.2±11.5 years	31.2±2.3 kg/m²	TJC: 14.5±10.5 SJC: 3.1±4.5	Biologic agent (anti-TNF) and supervised low calorie diet	Biologic agent (anti-TNF) and supervised healthy diet	24 weeks	5% Weight Loss Intervention: 77.8% Control: 39.7%	%MDA Intervention: 42.9% Control: 34.9%	p=0.043	Weight loss (>5%) improves probability of achieving MDA in patients with PsA commencing anti-TNF treatment
Pharmacological Weight Loss Methods in the Treatment of Psoriasis
Buysschaert et al (36)	Case series (n=7)	56.0±8.0 years	32.0±10.1 kg/m²	PASI: 12.0±5.9	Exenatide 5g subcutaneously twice daily (n=1) or liraglutide 1.2mg subcutaneously once daily (n=6)	-	18 weeks	After treatment: -4.4%^c	ΔPASI -2.8±2.9	p<0.05	Exenatide/liraglutide may improve moderate/severe psoriasis in obese patients with diabetes
Ahern et al (37)	Case series (n=7)	49.4±10.9 years	50.1±14.4 kg/m²	PASI: 8.7±9.2	Liraglutide 1.2mg subcutaneously once daily	-	10 weeks	After liraglutide: -5%^b	ΔPASI -3.7±5.3
Faurschou et al (38)	RCT (n=20)	51.3±13.1 years	36.1 ±9.6 kg/m²	PASI: 13.2±6.5	Liraglutide 1.8mg subcutaneously once daily	Placebo	8 weeks	Intervention: -4.1% Control: -1.5%	ΔPASI Intervention: -2.6±2.1 Control: -1.3±2.4	p=0.23	Liraglutide does not improve moderate/severe psoriasis in obese patients without diabetes
Bariatric Surgery in the Prevention of Psoriasis/PsA
Egeberg et al (39)	Cohort (n=13435)	28.2±10.2 years	-	-	Gastric bypass (n=12364) Gastric banding (n=1071)	No control group (compared pre- and post-surgery)	Pre-surgery Bypass: 12.8 years^c Banding: 9.3 years^c Post-surgery Bypass: 2.7 years^c Banding: 6.3 years^c	-	Incident Psoriasis Gastric bypass: Adjusted HR 0.52 (95%CI 0.33, 0.81) Gastric banding: Adjusted HR 1.23 (95%CI 0.40, 3.75) Incident PsA Gastric bypass: Adjusted HR 0.29 (95%CI 0.12, 0.71) Gastric banding: Adjusted HR 0.53 (95%CI 0.08, 3.56)	p=0.004 p=0.72 p=0.01 p=0.52	Risks of developing psoriasis and PsA are reduced with gastric bypass, but not gastric banding
Maglio et al (40)	Cohort (n=4009)	48.0±6.1 years	41.0±5.1 kg/m²	-	Gastric bypass (n=375) Gastric banding (n=262) Vertical banded gastroplasty (n=1354)	No intervention or supervised low calorie diet and exercise programme	Intervention: 18.7 years^d Control: 18.1 years^d	Intervention: -17.0%^e Control: +1.7%^e	Incident Psoriasis Adjusted HR 0.65 (95%CI, 0.47, 0.89) Incident PsA Adjusted HR 0.71 (95%CI, 0.38, 1.33)	p=0.008 p=0.287	Risk of developing psoriasis, but not PsA, is reduced with bariatric surgery

Results are presented as mean±standard deviation. Supervised low calorie diet refers to any hypocaloric diet supervised by a healthcare professional and designed to induce weight loss. Supervised healthy diet is any putative healthy diet which does not restrict caloric intake, but which is supervised by a healthcare professional. Maintenance diet is a hypocaloric diet designed to maintain weight loss induced by a more restrictive preceding hypocaloric diet. ^ano BMI or variance data available, ^bmedian % weight change ^cmean time participant observed, ^dmedian follow-up time, ^emean % change in BMI. %PASI75, proportion achieving PASI75; ΔPASI, mean change in PASI; BMI, body mass index; CI, confidence interval; HR, hazard ratio; MDA, minimal disease activity; PASI, psoriasis area and severity index; PsA, psoriatic arthritis; PUFA, polyunsaturated fatty acids; RCT, randomised control trial; SJC, swollen joint count; TJC, tender joint count; TNF, tumour necrosis factor; UVB, ultraviolet B

Table S4. Summary of risk-of-bias assessment methods and results.
Study	Design	RoB assessment tool	Random sequence generation	Blinding of outcome measurement	Incomplete outcome data	Selective reporting	Summary Assessment
Lifestyle (Diet/Physical Activity) Weight Loss Interventions in Psoriasis
Gisondi et al (27)	RCT	Cochrane RoB Assessment Tool	Low risk	Low risk	High risk	Low risk	Low risk
Al-Mutairi et al (28)	RCT	Cochrane RoB Assessment Tool	Unclear risk	Unclear risk	Unclear risk	Unclear risk	Unclear risk
Guida et al (29)	RCT	Cochrane RoB Assessment Tool	Low risk	High risk	High risk	Unclear risk	High risk
Naldi et al (30)	RCT	Cochrane RoB Assessment Tool	Low risk	Low risk	Low risk	Low risk	Low risk
Jensen et al (31)	RCT	Cochrane RoB Assessment Tool	Low risk	High risk	Low risk	Low risk	Low risk
Kimball et al (32)	RCT	Cochrane RoB Assessment Tool	Unclear risk	Low risk	High risk	Low risk	High risk
Del Giglio et al (33)	RCT	Cochrane RoB Assessment Tool	Low risk	Low risk	Low risk	Low risk	Low risk
Jensen et al (34)	Cohort study as follow-up to Jensen et al (31)	Cochrane RoB Assessment Tool	Low risk	High risk	High risk	Unclear risk	High risk
Lifestyle (Diet/Physical Activity) Weight Loss Interventions in PsA
Di Minno et al (35)	RCT	Cochrane RoB Assessment Tool	Low risk	Low risk	High risk	Low risk	Low risk
Pharmacological Loss Methods in the Treatment of Psoriasis
Buysschaert et al (36)	Case series	PROCESS Guidelines	-	-	-	-	Reporting criteria met
Ahern et al (37)	Case series	PROCESS Guidelines	-	-	-	-	Reporting criteria met
Faurschou et al (38)	RCT	Cochrane RoB Assessment Tool	Low risk	Low risk	Low risk	High risk	Low risk
Bariatric Surgery in the Prevention of Psoriasis/PsA
Egeberg et al (39)		Cohort	Cochrane RoB Assessment Tool	High risk	Low risk	Low risk	Low risk	Low risk
Maglio et al (40)		Cohort	Cochrane RoB Assessment Tool	High risk	Low risk	Low risk	High risk	High risk

NOTE: For Cochrane RoB Assessment Tool, within-study summary risk of bias was first judged based on risk of bias in key domains. Between-study risk of bias was then assessed based on whether the proportion of information from studies at high risk of bias would likely be sufficient to influence the interpretation of results (25). PsA, psoriatic arthritis; RCT, randomised control trial; RoB, risk of bias.

Table S5. Summary assessment of risk of bias.
Study	Random sequence generation	Blinding of outcome measurement	Incomplete outcome data	Selective reporting	Within study assessment
Al-Mutairi et al	Unclear risk	Unclear risk	Unclear risk	Unclear risk	Unclear risk
Del Giglio et al	Low risk	Low risk	Low risk	Low risk	Low risk
DiMinno et al	Low risk	Low risk	High risk	Low risk	Low risk
Egeberg et al	High risk	Low risk	Low risk	Low risk	Low risk
Faurschou et al	Low risk	Low risk	Low risk	High risk	Low risk
Gisondi et al	Low risk	Low risk	High risk	Low risk	Low risk
Guida et al	Low risk	High risk	High risk	Unclear risk	High risk
*Jensen et al* (1)**	Low risk	High risk	Low risk	Low risk	Low risk
*Jensen et al* (2)**	Low risk	High risk	High risk	Unclear risk	High risk
Kimball et al	Unclear risk	Low risk	High risk	Low risk	High risk
Maglio et al	High risk	Low risk	Low risk	High risk	High risk
Naldi et al	Low risk	Low risk	Low risk	Low risk	Low risk
Summary Assessment of All Studies	-	-	-	-	High risk

NOTE: Within-study summary risk of bias was first judged based on risk of bias in key domains. Between-study risk of bias was then assessed based on whether the proportion of information from studies at high risk of bias would likely be sufficient to influence the interpretation of results (25).

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Does Weight Loss Reduce the Severity and Incidence of Psoriasis or Psoriatic Arthritis?

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