Elicit: Clinical Outcomes of TNF Inhibition in RA and Psoriasis

Clinical Outcomes of TNF Inhibition in RA and Psoriasis

Identify clinical evidence linking TNF inhibition to outcomes in rheumatoid arthritis and psoriasis

Abstract

TNF inhibitors demonstrate substantial therapeutic efficacy for psoriatic arthritis and psoriasis, with 37% of csDMARD-inadequate responders achieving clinical improvement (ACR50) versus 8% with placebo (RR 5.63, 95% CI 3.98 to 7.96). For moderate-to-severe plaque psoriasis, PASI 75 response rates reach 80-91% with infliximab compared to 3% with placebo, with therapeutic effects appearing within 4 weeks. However, paradoxical new-onset or worsening psoriasis emerges as a recognized adverse event in patients receiving TNF inhibitors for rheumatoid arthritis, occurring at 1.04 per 1000 person-years compared to 0 per 1000 person-years with traditional DMARDs. Adalimumab shows 4.6-fold higher incidence of paradoxical psoriasis than etanercept and 3.5-fold higher than infliximab, though no statistically significant differences in therapeutic effectiveness exist among anti-TNF agents. Most patients (66%) developing paradoxical psoriasis can continue TNF inhibitor therapy with concurrent psoriasis treatment, balancing control of the primary indication against induced skin disease.

Methods

We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 8 key aspects that mattered most to the research question.

Records from Elicit search

n = 200: Papers screened based on target population, intervention type, clinical outcomes, study design, population age, study type (human research), sample size adequacy, publication type.
n = 190: Papers screened out.
n = 10: Papers included for extraction.

Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.

We ran this query: "Identify clinical evidence linking TNF inhibition to outcomes in rheumatoid arthritis and psoriasis". The search returned 200 total results from Elicit.

Screening

We screened in sources based on their abstracts that met these criteria:

Target Population - Disease: Patients diagnosed with rheumatoid arthritis and/or psoriasis?
Intervention Type: Study involves TNF inhibitor therapy (adalimumab, etanercept, infliximab, certolizumab pegol, or golimumab)?
Clinical Outcomes: Study reports clinical outcomes such as disease activity measures, symptom improvement, quality of life, or safety outcomes?
Study Design: Randomized controlled trial, cohort study, case-control study, systematic review, or meta-analysis?
Population Age: Study population includes adult patients (≥18 years of age)?
Study Type - Human Research: Conducted in human participants?
Sample Size Adequacy: Includes 10 or more patients?
Publication Type: Full-text article?

Data extraction

Key data columns extracted from each paper:

Study Design: Type of study, comparison groups, blinding status, duration of follow-up, key methodological features relevant to assessing TNF inhibitor effects.
Target Condition: Condition(s) addressed in relation to TNF inhibition.
Patient Population: Key characteristics of the study population relevant to TNF inhibition outcomes in RA and psoriasis.
TNF Inhibitor Details: Information about TNF inhibitor treatment.
Primary Outcomes: Primary clinical outcomes used to assess TNF inhibition effects.
Safety Findings: Safety and adverse event data related to TNF inhibition.
Key Evidence: Main findings about the link between TNF inhibition and clinical outcomes.
Study Limitations: Key limitations and biases that could affect interpretation.

Results

Characteristics of Included Studies

The review included 10 studies published between 2000 and 2025, comprising: 5 randomized controlled trials, 3 meta-analyses/systematic reviews, 1 prospective registry study, and 1 retrospective cohort study.

Efficacy in Psoriatic Arthritis

TNF inhibitors demonstrated substantial clinical benefit in psoriatic arthritis across multiple outcome domains. In csDMARD-inadequate responders, TNFi produced large improvements in clinical response at 12 weeks, with 37% achieving ACR50 compared to 8% with placebo (RR 5.63, 95% CI 3.98 to 7.96). Physical function improved with TNFi treatment at 24 weeks, with a mean change of -0.14 points on the Health Assessment Questionnaire compared to placebo.

Efficacy in Psoriasis

TNF inhibitors demonstrated high efficacy for moderate-to-severe plaque psoriasis, with infliximab showing the highest probability of PASI 75 achievement. TNFi produced durable responses over one year.

Safety Profile

The safety profile of TNF inhibitors in psoriatic arthritis appeared favorable. Serious adverse events were slightly higher among TNFi-treated patients compared to placebo, but withdrawals due to adverse events were also slightly higher.

Paradoxical Psoriasis During TNF Inhibitor Therapy

Despite TNF inhibitors’ efficacy, paradoxical psoriasis emerged as an adverse event in patients treated for other inflammatory conditions. The incidence varied by agent, with adalimumab showing significantly higher rates than etanercept and infliximab.

Synthesis

The evidence reveals a paradox: TNF inhibitors effectively treat psoriatic arthritis and moderate-to-severe psoriasis while inducing or exacerbating psoriasis in other contexts. Immunopathogenesis differs between therapeutic response and paradoxical induction, suggesting separate underlying mechanisms.