Obesity and psoriasis are closely interlinked through chronic systemic inflammation, with excess adipose tissue producing pro-inflammatory cytokines that worsen psoriatic skin lesions. Patients with obesity often experience more severe psoriasis and reduced responses to biologic treatments compared to those with normal body weight. Understanding how obesity inflammation impacts biologic treatments for psoriasis is essential for optimising therapeutic outcomes. This article explores the inflammatory mechanisms connecting obesity and psoriasis, examines how body weight affects biologic efficacy, reviews treatment options for patients with elevated BMI, and discusses weight management strategies and dosing considerations to improve disease control.

How Obesity Affects Inflammation in Psoriasis

Obesity and psoriasis share a complex bidirectional relationship mediated through chronic low-grade systemic inflammation. Adipose tissue, particularly visceral fat, functions as an active endocrine organ and harbours infiltrating immune cells that secrete pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-17 (IL-17). These cytokines directly contribute to the inflammatory cascade underlying psoriatic skin lesions, creating a self-perpetuating cycle of inflammation.

Research demonstrates that individuals with obesity experience more severe psoriasis, with higher Psoriasis Area and Severity Index (PASI) scores compared to those with normal body mass index (BMI). The excess adipose tissue produces adipokines such as leptin and resistin, which may promote T-helper 17 (Th17) cell differentiation—a key pathway in psoriasis pathogenesis. Conversely, levels of adiponectin, an anti-inflammatory adipokine, are reduced in obesity, further tipping the balance towards inflammation.

The metabolic dysfunction associated with obesity, including insulin resistance and dyslipidaemia, compounds the inflammatory burden. This metabolic syndrome cluster is significantly more prevalent in psoriasis patients than in the general population. Observational studies suggest associations between obesity and increased psoriasis risk and severity, though these relationships are complex and influenced by genetic and environmental factors. The inflammatory milieu created by excess adiposity may worsen existing psoriasis and potentially contribute to disease onset in genetically predisposed individuals.

Key inflammatory mechanisms include:

• Enhanced production of IL-17 and IL-23 by immune cells within adipose tissue, central to psoriatic plaque formation

• Increased oxidative stress from adipose tissue

• Activation of nuclear factor-kappa B (NF-κB) signalling pathways

• Dysregulation of the immune system favouring pro-inflammatory responses

Understanding this inflammatory interplay is crucial for optimising treatment strategies, as addressing obesity may help reduce the overall inflammatory burden and improve psoriasis control. NICE guideline CG153 (Psoriasis: assessment and management) recommends assessing and managing cardiovascular risk factors, including obesity, as part of comprehensive psoriasis care.

Impact of Body Weight on Biologic Treatment Response

Body weight significantly influences the pharmacokinetics and clinical efficacy of biologic therapies for psoriasis. Patients with obesity consistently demonstrate reduced treatment responses across multiple biologic classes, with studies showing that higher BMI correlates with lower rates of achieving PASI 75 (75% improvement in disease severity) and PASI 90 responses. This diminished efficacy stems from several pharmacological and biological factors.

The volume of distribution for biologic agents increases proportionally with body weight, and higher body weight is associated with increased drug clearance, potentially resulting in lower serum drug concentrations when standard fixed doses are administered. Weight-based or weight-banded dosing regimens may help maintain drug exposure across different body weights. Additionally, the heightened inflammatory state associated with obesity may require higher drug exposure to achieve adequate disease suppression.

Clinical trial post-hoc analyses and real-world data, including evidence from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), reveal that patients with elevated BMI are less likely to achieve optimal skin clearance compared to those with normal weight. This effect varies by drug class and mechanism of action. The increased inflammatory cytokine load from adipose tissue may necessitate higher drug concentrations to neutralise the excess inflammatory mediators.

Factors affecting treatment response in obesity:

• Altered drug distribution and clearance rates leading to lower serum drug exposure

• Increased inflammatory cytokine production requiring higher drug exposure

• Larger volume of distribution reducing drug concentrations

• Higher baseline disease severity requiring more intensive treatment

Real-world evidence from UK dermatology centres confirms these findings, with obesity identified as a predictor of reduced biologic treatment response. NICE Technology Appraisals assess biologics at their licensed doses and indications, with treatment eligibility based primarily on disease severity (PASI and Dermatology Life Quality Index scores) rather than body weight. Patients should be counselled that achieving optimal weight may enhance treatment effectiveness and improve long-term disease control.

Which Biologic Treatments Are Used for Psoriasis in Patients with Obesity

Biologic therapies demonstrate varying efficacy profiles in patients with obesity and psoriasis. Evidence suggests that IL-17 and IL-23 inhibitors may maintain efficacy across BMI categories more consistently than TNF-α inhibitors, though individual patient factors and treatment history remain important considerations. Treatment selection should follow NICE Technology Appraisals and British Association of Dermatologists (BAD) guidance, taking into account disease severity, presence of psoriatic arthritis, comorbidities, patient preference, and prior treatment response.

IL-23 inhibitors such as guselkumab, risankizumab, and tildrakizumab have demonstrated maintained efficacy across BMI categories in clinical trials. These agents target the p19 subunit of IL-23, a cytokine elevated in obesity-associated inflammation. Post-hoc analyses of clinical trials suggest that IL-23 inhibitors achieve PASI 90 responses in patients with elevated BMI at rates approaching those seen in normal-weight individuals. Risankizumab has shown consistent efficacy regardless of baseline weight in head-to-head comparisons such as the IMMerge trial.

IL-17 inhibitors including secukinumab, ixekizumab, and brodalumab also perform well in patients with elevated BMI. These agents directly block IL-17A (or its receptor), a cytokine whose levels correlate with adiposity. Clinical data suggest that whilst absolute response rates may be slightly lower in obesity, IL-17 inhibitors still achieve meaningful disease control. Ixekizumab has demonstrated resilience to the negative impact of obesity on treatment outcomes in subgroup analyses.

TNF-α inhibitors such as adalimumab, etanercept, and infliximab show more pronounced reductions in efficacy with increasing body weight in some studies. Infliximab, administered by weight-based dosing (5 mg/kg intravenously), may help maintain drug exposure across weight categories, though evidence remains mixed. MHRA-approved biosimilar TNF inhibitors follow similar patterns.

IL-12/23 inhibitor ustekinumab uses weight-banded dosing (45 mg for patients ≤100 kg; 90 mg for those >100 kg), which helps maintain efficacy across weight categories. This dosing strategy has proven effective in clinical practice.

Treatment choice should be individualised according to NICE Technology Appraisals, BAD guidance, and patient-specific factors. Refer to the Summary of Product Characteristics (SmPC) for each biologic via the electronic Medicines Compendium (EMC) or MHRA website for full prescribing information, licensed indications, and dosing regimens.

Weight Management Strategies to Improve Psoriasis Outcomes

Weight reduction represents a valuable adjunctive intervention for improving psoriasis control and enhancing biologic treatment responses. Clinical studies demonstrate that even modest weight loss of 5–10% body weight can lead to significant improvements in PASI scores and increased likelihood of achieving treatment targets. Integrating weight management into psoriasis care should be considered a therapeutic priority.

Structured weight loss programmes combining dietary modification and physical activity have shown promise. Randomised controlled trials have found that patients following calorie-controlled diets alongside biologic therapy achieved significantly better PASI responses than those receiving biologics alone. The anti-inflammatory effects of weight loss complement pharmacological treatment, reducing the overall cytokine burden and potentially allowing treatment optimisation in some cases.

Evidence-based weight management approaches include:

• Dietary interventions: Mediterranean-style diets rich in omega-3 fatty acids, fruits, vegetables, and whole grains have demonstrated anti-inflammatory properties. Reducing processed foods and refined carbohydrates helps address insulin resistance common in psoriasis patients. Individualised dietary advice from a registered dietitian is recommended.

• Physical activity: Regular moderate-intensity exercise (150 minutes weekly, as per UK Chief Medical Officers' Physical Activity Guidelines) reduces systemic inflammation, improves insulin sensitivity, and supports weight loss. Activities should be tailored to individual capabilities and joint health, particularly in those with psoriatic arthritis. Refer to NHS physical activity guidance for patient resources.

• Behavioural support: Referral to NHS weight management services provides structured support and accountability. Options include Tier 2 community services (lifestyle interventions), the NHS Digital Weight Management Programme, and Tier 3 specialist weight management services for complex cases.

• Pharmacological options: In selected patients meeting specific criteria, anti-obesity medications may be considered following specialist assessment. NICE Technology Appraisal TA875 recommends semaglutide 2.4 mg (Wegovy) for weight management in adults with at least one weight-related comorbidity and either BMI ≥35 kg/m² or BMI 30–34.9 kg/m² with specific criteria. Liraglutide 3 mg (Saxenda) may be available in some areas subject to local commissioning decisions. Orlistat is licensed for BMI ≥30 kg/m² (or ≥28 kg/m² with risk factors). Refer to NICE guidance and local formularies for current recommendations and access criteria.

Bariatric surgery represents an option for patients with severe obesity meeting NICE guideline CG189 criteria: BMI ≥40 kg/m² or BMI 35–39.9 kg/m² with significant obesity-related comorbidities, who have not achieved adequate weight loss through non-surgical interventions. Studies show substantial psoriasis improvement post-bariatric surgery, with some patients achieving significant disease control. Dermatologists should consider referral to Tier 3/4 weight management services when managing patients with concurrent severe obesity and psoriasis.

Healthcare professionals should approach weight discussions sensitively, focusing on health benefits and recognising that obesity itself may be exacerbated by psoriasis through reduced mobility, psychological distress, and certain medications. Multidisciplinary collaboration involving dermatology, dietetics, and primary care optimises outcomes. Refer to NHS weight management service pathways and NICE CG189 for comprehensive guidance.

Dosing Considerations for Biologics in Patients with Elevated Body Weight

Optimising biologic dosing in patients with elevated body weight requires careful consideration of pharmacokinetic principles, licensed indications, and emerging evidence. Most biologics for psoriasis are licensed at fixed doses regardless of weight, though some agents offer weight-based or weight-banded dosing. Any dosing adjustments beyond the licensed regimen constitute off-label use and require appropriate governance, documentation, and shared decision-making.

Weight-based and weight-banded dosing strategies: Infliximab is administered by weight-based dosing (5 mg/kg intravenously at weeks 0, 2, and 6, then every 8 weeks), which maintains consistent drug exposure across body weights. The Summary of Product Characteristics (SmPC) permits dose escalation or shortened intervals in patients with inadequate response. Ustekinumab employs weight-banded dosing: patients ≤100 kg receive 45 mg subcutaneously, whilst those >100 kg receive 90 mg, at weeks 0 and 4, then every 12 weeks. This strategy is supported by pharmacokinetic modelling and clinical outcomes data. The SmPC also permits dosing every 8 weeks in patients with inadequate response.

For fixed-dose biologics, including most IL-17 and IL-23 inhibitors, the licensed regimens do not vary by weight. Some agents offer flexibility within their licensed indications: for example, secukinumab permits monthly maintenance dosing (300 mg every 4 weeks) in patients with inadequate response to every-12-week dosing. Always consult the current UK SmPC via the electronic Medicines Compendium (EMC) or MHRA website for each agent's licensed dose options and permitted adjustments.

Practical dosing considerations include:

• Therapeutic drug monitoring: Measuring serum drug levels and anti-drug antibodies can identify patients with low drug exposure, though routine monitoring is not standard practice in UK dermatology and evidence supporting its use in psoriasis is limited. Specialist advice should be sought if considering this approach.

• Response assessment: Regular PASI scoring and patient-reported outcomes (e.g., Dermatology Life Quality Index) help identify suboptimal responses that may warrant treatment review.

• Licensed interval adjustment: Where the SmPC permits shortened dosing intervals or increased frequency for inadequate response, this may be considered following appropriate assessment.

• Switching strategy: If optimisation within the licensed regimen is not effective, switching to an alternative biologic may be preferable, guided by NICE Technology Appraisals and BAD guidance.

Safety considerations must be weighed, as higher drug exposure may increase the risk of infections and other adverse effects. Refer to the SmPC safety sections for each agent. The MHRA and EMA have approved specific dosing regimens for each biologic; any adjustments beyond these constitute off-label use requiring appropriate governance, documentation of rationale, and informed patient consent.

From a health economics perspective, dose intensification significantly increases treatment costs and must be justified through clinical need. NICE Technology Appraisals assess biologics at their licensed doses, and deviation from these may require individual funding requests or specialist commissioning approval. Clinicians should document the rationale for any dosing modifications, including previous treatment responses, disease severity, functional impairment, and impact on quality of life.

When to consider treatment review:

• Partial response (e.g., PASI 50–75) on standard dosing after an adequate trial period

• Secondary loss of response after initial good control

• Severe disease with significant functional impairment despite standard treatment

• Documented low serum drug levels on therapeutic monitoring (if performed)

Patients should be counselled that weight loss may improve treatment response and potentially allow dose optimisation over time, providing additional motivation for weight management efforts. Close collaboration between dermatology, pharmacy, and commissioning teams ensures that treatment decisions are clinically appropriate, evidence-based, and sustainable within NHS resources.

Important safety information: If you experience any side effects whilst taking a biologic medicine, report them to your healthcare team. You can also report suspected side effects directly via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk or by downloading the Yellow Card app.

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