040 An analysis of malignancy risk in the clinical development programme of cladribine tablets in patients with relapsing multiple sclerosis
Bibliographic record
Abstract
Introduction An independent meta-analysis; Pakpoor et al. Neurol Neuroimmunol Neuroinflamm 2015;2:e158) in Phase III trials (with a 2 year duration) of disease modifying drugs (DMDs) in patients with relapsing multiple sclerosis found no increased rate of malignancy with cladribine tablets (CT) versus other DMD treatments. Data from additional trials involving CT 3.5 mg/kg (CT3.5) and a safety registry (up to 8 years’ follow-up) allow further insights into malignancy risk. Objective is to assess malignancy risk with CT3.5 monotherapy and placebo (PBO) in data from 3 Phase III trials and a registry, and compare the incidence rate with a global database. Methods The CT 3.5 population comprised 923 patients (3433 patient-years’ [PY] total exposure time) and the PBO group comprised 641 patients (2026 PY). Individual case reports of malignancies were reviewed by independent, blinded adjudication committee. Standardised incidence ratios (SIR) were calculated using the GLOBOCAN reference population (excluding non-melanoma skin cancers [NMSCs]) and a Danish reference population for NMSC rates. Results The incidence per 100 PY of confirmed malignancy was CT3.5 0.293 (95%CI 0.158–0.544) and PBO 0.148 (95%CI 0.048–0.460); the risk difference 95% CI included 0 (−0.166–0.414). The CT 3.5 malignancy SIR was almost identical (0.97, 95% CI 0.44–1.85) to the GLOBOCAN matched reference population. The PBO group SIR was numerically lower (0.48, 95% CI 0.14–1.53). There were no cases of haematological, lymphoproliferative or virus-induced cancers. There was no clustering of specific tumour types, and the incidence of skin cancer was not increased after treatment with CT3.5 versus PBO. The incidence of malignancies with CT3.5 was constant and did not increase over time. Conclusion Analysis of malignancy rates in a cohort that includes patients with up to 8 years’ follow-up confirms the Conclusion of the earlier meta-analysis; the incidence of malignancies with CT3.5 is similar to a matched reference population.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".