Recent findings show that ustekinumab may be a possible solution for many primary non responding psoriatic arthritis patients who failed all tnf blockers treatments (not patients who were forced to suspend the treatment because of negative side effects). Nevertheless there're still people who do not respond to ustekinumab even at 90 mg dosage.
Can anybody tell me the reason of this failure?
Can this failure be due to a "genetic settings" of patients' autoimmune system which can defeat monoclonal antibodies which are used both with ustekinumab as with tnf alpha blockers?
The FDA and EMA have approved the interleukin (IL) 12/23 inhibitor ustekinumab for adults with active psoriatic arthritis who have not responded adequately to previous nonbiological disease-modifying antirheumatic drug therapy.
The following gene polymorphisms are thought to be associated with psoriasis and psoriatic arthritis:
· Tumor necrosis factor (TNF)-alpha promoter
· MHC class I-chained related gene A (MICA)
· Caspase-activating recruitment domain (CARD) 15
· Interleukin (IL)-12/IL-23p40 and IL-23 receptor
So it is conceivable that non-responders might fall in categories where gene polymorphism is not IL-12/IL-23.
From the clinical point of view neither psoriasis nor psoriatic arthrtitis (PSA) are a homogenous disease due to the large variety of clinical manifestation, course of the disease and response to treatment. You may know that spine involvement is less responding to treatment compared to peripheral oligoarthritis.
From the clinical point of view sometime nonresponders can be explained by very simple issues such as body weight or smoking. Considering the exprience with ustekinumab in psoriasis, those patients within an inflammatory acute stage benefit most. I do not know any detailed study on the subject, but it could be the same with PSA.
I hope this will help you.
On the pivotal studies Psummit 1 and 2 ustekinumab proved to be efficacious as first line but also after TNF failure. Altough as expected it is less efficacious as 2nd or 3rd line biologic (like what it happens with 2nd and 3rd line TNF).
Dear colleagues, many thanks for your interesting answers.
All my best, Catina
Carissima Catina, nella nostra piccola esperienza abbiamo trattato finora 16 pazienti affetti da artrite psoriasica con ustekinumab, che non avevano precedentemente risposto all'antiTNF. Nella mia esperienza purtroppo tutti i pazienti non si sono mostrati responsivi al nuovo farmaco, sulla componente articolare, ed appare anche difficile spiegarsi i motivi del fallimento. Speriamo che gli anti-IL17 possano migliorare le nostre aspettative.
Alla prossima, Angelo
Grazie mille Angelo. Speriamo in questo Jak-treatment di cui mi parlavi proprio tu tempo fa.
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