Ariad Pharmaceuticals Inc fka ARIA

[LUMA14]

Risk of arterial and venous occlusive events in chronic myeloid leukemia patients treated with new generation BCR-ABL tyrosine kinase inhibitors: A systematic review and meta-analysis.

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Abstract
BACKGROUND:
A previous meta-analysis demonstrated that 3 of the new-generation BCR-ABL tyrosine kinase inhibitors (TKIs) (dasatinib, nilotinib and ponatinib) are associated with an increased risk of vascular occlusive events in patients with Ph+ chronic myeloid leukemia compared with imatinib. This meta-analysis of randomized controlled trials aims at assessing these risks separately.
METHODS:
The literature search was performed by two independent reviewers following the previous protocol (PROSPERO 2014:CRD42014014147). A random-effects model and a fixed-effect model were used according to the characteristics of the included studies. Peto odds ratios with 95%CI were computed.
RESULTS:
Overall, 4.78% of patients developed arterial occlusive events with new generation TKIs compared with 0.96% with imatinib.
Ponatinib (ORPETO:3.26; 95%CI:1.12 to 9.50),
nilotinib (ORPETO: 3.69; 95%CI:2.29 to 5.95) and
dasatinib (ORPETO:3.32; 95%CI:1.37 to 8.01) are all associated with a higher risk of arterial occlusive events than imatinib.
Venous occlusive events occur in 0.72% of patients treated with new generation TKIs and in 0.27% of imatinib-treated patients. Overall, a trend toward an increase of the rate of venous occlusive events with new-generation TKIs (ORPETO:2.17; 95%CI:0.90 to 5.25) was highlighted but stratifications by treatment gave nonsignificant results.
CONCLUSIONS:
Vascular occlusive events associated with new-generation BCR-ABL TKIs are driven by arterial occlusive events.

The better the performance the higher the side effect...
No new insight in chemistry and medcine since paracelsus.
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Sola dosis facit venenum.

(German: "Die Dosis macht das Gift.") - [33]

or

The dose makes the poison.

Competitors of 2nd. gen TKI are not really better in side effects?