321 Cancer risk with topical pimecrolimus and tacrolimus for atopic dermatitis: systematic review and Bayesian meta-analysis
Bibliographic record
Abstract
Abstract Atopic dermatitis affects millions worldwide and is effectively managed by topical treatments, including topical calcineurin inhibitors, pimecrolimus and tacrolimus. In 2005 and 2011, the FDA released reviews associating topical calcineurin inhibitors with a theoretical cancer risk, albeit an uncertain association. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors. We systematically identified randomized controlled trials, comparative, and non-comparative non-randomized studies from database inception to 6 June 2022, from MEDLINE, EMBASE, GREAT, LILACS, ICTRP, FDA, EMA, company registers and relevant citations. We included studies in any language addressing the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors for greater than 3 weeks. We excluded split-body studies. We conducted a Bayesian meta-analysis and used the GRADE approach to determine the certainty of the evidence. A multidisciplinary panel including patients, advocacy groups and care providers, set an a priori threshold of 1 in 1000 risk difference as a clinically important effect. We analysed 121 studies (52 randomized controlled trials and 69 non-randomized studies) including 3.4 million patents followed for a mean of 11 months (range: 0.7–120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was neither different from controls (absolute risk 4.70 per 1000 with topical calcineurin inhibitor exposure vs. 4.56 per 1000 without; odds ratio 1.03 [95% credible interval 0.94–1.11], moderate-certainty evidence) nor the general US population (4.6 per 1000). Findings were similar in infants, children, and adults, and were robust to trial sequential, subgroup and sensitivity analyses. Among infants, children and adults with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the management of patients with atopic dermatitis. Our findings provide actional information to inform updated clinical practice guidelines, product labels and continuing education for care providers, to clarify the safe usage of topical calcineurin inhibitors.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.024 | 0.058 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.014 | 0.045 |
| Bibliometrics | 0.010 | 0.008 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".