# 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 using:
- Target Population - Disease
- Intervention Type
- Clinical Outcomes
- Study Design
- Population Age
- Study Type - Human Research
- Sample Size Adequacy
- Publication Type

### Papers screened out
- n = 190

### Papers included for extraction
- n = 10

## Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/).

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. We retrieved 200 papers most relevant to the query for screening.

## Screening

We screened in sources based on their abstracts that met these criteria:
- **Target Population - Disease**: Does the study include patients diagnosed with rheumatoid arthritis and/or psoriasis?
- **Intervention Type**: Does the study involve TNF inhibitor therapy (adalimumab, etanercept, infliximab, certolizumab pegol, or golimumab)?
- **Clinical Outcomes**: Does the study report clinical outcomes such as disease activity measures, symptom improvement, quality of life, or safety outcomes?
- **Study Design**: Is the study design a randomized controlled trial, cohort study, case-control study, systematic review, or meta-analysis?
- **Population Age**: Does the study population include adult patients (≥18 years of age)?
- **Study Type - Human Research**: Is this a study conducted in human participants (not in vitro, animal, or preclinical research)?
- **Sample Size Adequacy**: Does the study include 10 or more patients (not a case report or small case series with <10 patients)?
- **Publication Type**: Is this a full-text article (not a conference abstract, letter, editorial, or commentary)?

## Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions for each column.

### Study Design:
- Type of study (RCT, cohort, case-control, registry study, meta-analysis, etc.)
- Comparison groups (placebo, active comparator, historical controls, etc.)
- Blinding status
- Duration of follow-up
- Key methodological features relevant to assessing TNF inhibitor effects

### Target Condition:
- Rheumatoid arthritis (as primary indication)
- Psoriasis (as primary indication)
- Psoriatic arthritis
- Psoriasis as adverse event in RA patients
- Other related conditions

### Patient Population:
- Sample size
- Age range/mean age
- Disease severity at baseline
- Disease duration
- Prior treatment history (DMARDs, biologics, etc.)
- Any relevant comorbidities
- Geographic/clinical setting

### TNF Inhibitor Details:
- Name of TNF inhibitor(s) studied (infliximab, adalimumab, etanercept, golimumab, certolizumab)
- Dosage and administration route
- Treatment duration
- Whether used as monotherapy or combination therapy
- Any dose escalations or modifications
- Comparison between different TNF inhibitors if applicable

### Primary Outcomes:
- Outcome measure names (PASI, ACR response, DAS28, PGA, etc.)
- How outcomes were defined and measured
- Time points of assessment
- Primary endpoint results with effect sizes, confidence intervals, and statistical significance
- Response rates or mean changes from baseline

### Safety Findings:
- Serious adverse events
- Treatment-related adverse events
- Infections (including opportunistic infections)
- Paradoxical reactions (e.g., psoriasis in RA patients)
- Discontinuation rates due to adverse events
- Any condition-specific safety concerns
- Comparison of safety profiles between different TNF inhibitors

### Key Evidence:
- Direction and magnitude of treatment effects
- Clinical significance of observed effects
- Time to response/onset of effect
- Durability of response
- Factors that modify treatment response
- Any unexpected or paradoxical findings
- Comparative effectiveness between TNF inhibitors
- Authors’ conclusions about TNF inhibition efficacy/safety

### Study Limitations:
- Sample size limitations
- Short follow-up duration
- Selection bias or generalizability concerns
- Missing data or dropout rates
- Confounding factors not controlled for
- Measurement bias or outcome assessment issues
- Funding source and potential conflicts of interest
- Authors’ stated limitations

## 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. These studies addressed TNF inhibition in three distinct contexts: therapeutic use for psoriatic arthritis, therapeutic use for psoriasis, and paradoxical psoriasis development during TNF inhibitor therapy for other conditions.

| Study | Full text retrieved? | Study Type | Target Condition | TNF Inhibitor(s) | Sample Size | Primary Outcomes |
|-------|---------------------|------------|------------------|-------------------|-------------|------------------|
| L. Lemos et al., 2014 | No | Systematic review and meta-analysis | Psoriatic arthritis | Adalimumab, etanercept, golimumab, infliximab | Not mentioned | ACR20, ACR50, PsARC, PASI75 |
| G. Cagnotto et al., 2025 | No | Systematic review and meta-analysis of RCTs | Psoriatic arthritis | TNFi (specific agents not mentioned) | 7857 | ACR50, HAQ, SF-36 MCS, Sharp/Van der Heijde-PsA |
| E. Shmidt et al., 2012 | No | Retrospective cohort study | Psoriasis as adverse event | Infliximab, adalimumab, etanercept | 56 | Complete or partial response |
| Mark Harrison et al., 2008 | Yes | Prospective observational cohort (registry) | Rheumatoid arthritis; psoriasis as adverse event | Etanercept, infliximab, adalimumab | 9826 anti-TNF, 2880 DMARD | Incidence of new-onset psoriasis |
| Angelique N. Collamer & D. Battafarano, 2010 | No | Systematic literature review | Psoriasis as adverse event in RA and other conditions | Infliximab, adalimumab, etanercept | 207 | Not mentioned |
| P. Mease et al., 2000 | No | Randomized controlled trial | Psoriatic arthritis and psoriasis | Etanercept 25 mg twice-weekly subcutaneous | 60 | PsARC, ACR20, PASI |
| N. Bansback et al., 2009 | No | Systematic review and meta-analysis | Psoriasis | Infliximab, adalimumab, etanercept | Not mentioned | PASI |
| U. Chaudhari et al., 2001 | No | Randomized controlled trial | Psoriasis | Infliximab 5 mg/kg and 10 mg/kg intravenous | 33 | Physician’s Global Assessment |
| K. Reich et al., 2005 | No | Randomized controlled trial | Psoriasis | Infliximab 5 mg/kg via infusion | 378 | PASI |
| K. Thorlund et al., 2012 | No | Indirect comparison meta-analysis | Psoriatic arthritis | Adalimumab, etanercept, golimumab, infliximab | Not mentioned | PsARC, HAQ, PASI |

### Effects of TNF Inhibitors

#### 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). An earlier meta-analysis found that more patients achieved ACR20, ACR50, and PsARC responses with anti-TNF agents compared to controls at 24 weeks, with etanercept and infliximab showing higher ACR70 response rates.

Physical function improved with TNFi treatment, and at 24 weeks, 32% of TNFi-treated patients achieved minimal disease activity compared to 9% with placebo (RR 3.76, 95% CI 2.39 to 5.92).

#### Efficacy in Psoriasis

TNF inhibitors demonstrated high efficacy for moderate-to-severe plaque psoriasis, with infliximab showing the highest probability for achieving PASI 75. Improvements were maintained over one year.

#### Safety Profile

The safety profile of TNF inhibitors in psoriatic arthritis appeared favorable. However, TNFi slightly increased withdrawals due to adverse events.

#### Paradoxical Psoriasis During TNF Inhibitor Therapy

Despite TNF inhibitors’ efficacy in treating psoriasis, paradoxical new-onset or worsening psoriasis emerged as a recognized adverse event in patients receiving these agents for other indications.

## Synthesis

The evidence reveals a paradox: TNF inhibitors demonstrate substantial efficacy in treating both psoriatic arthritis and moderate-to-severe psoriasis, yet simultaneously induce or exacerbate psoriasis in patients treated for other inflammatory conditions. This contradiction can be reconciled through several mechanistic and contextual considerations.

## References

- E. Shmidt et al. (2012). Psoriasis and palmoplantar pustulosis associated with tumor necrosis factor-α inhibitors: the Mayo Clinic experience, 1998 to 2010. Journal of American Academy of Dermatology

- Mark Harrison et al. (2008). Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor α therapy: results from the British Society for Rheumatology Biologics Register. Annals of the Rheumatic Diseases

- Angelique N. Collamer & D. Battafarano (2010). Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: clinical features and possible immunopathogenesis. Seminars in Arthritis & Rheumatism

- P. Mease et al. (2000). Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. The Lancet

- N. Bansback et al. (2009). Efficacy of Systemic Treatments for Moderate to Severe Plaque Psoriasis: Systematic Review and Meta-Analysis. Dermatology

- U. Chaudhari et al. (2001). Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. The Lancet

- K. Reich et al. (2005). Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. The Lancet

- K. Thorlund et al. (2012). Anti-tumor necrosis factor (TNF) drugs for the treatment of psoriatic arthritis: an indirect comparison meta-analysis. Biologics : targets & therapy

- L. Lemos et al. (2014). Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and meta-analysis of efficacy, effectiveness and safety. Rheumatology International

- G. Cagnotto et al. (2025). Tumor necrosis factor (TNF) inhibitors for psoriatic arthritis. Cochrane Database of Systematic Reviews