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F-2015-DH4 (April: Psoriasis)

PostPosted: Tue Mar 31, 2015 6:08 pm
by CFH
http://dermatologicahelvetica.com/en/ar ... clesID=113 (Page 8)

1-Which biologic for psoriasis in childhood ? / Quel biologique donner chez les enfants ?

2-PASI makes the decision for eliciting biologics / Le PASI l'emporte sur le DLQI pour initier un traitement par les biologiques

3-Targeting IL23 alone: it works! / Cibler Il-23 seul: ça marche !

3-Psoriasis NOT associated with cardiovascular risk ! / Le psoriasis n'est pas associé avec les risques cardiovasculaires

4-The new concept of "happy" drug survival / La quailté de vie des patients qui prennent les biologiques.

5-Regular physical activity may lower the risk of psoriasis / L'activité physique régulière peut diminuer le risque d'avoir le psoriasis

Schreiben Sie ein Kommentar !
Faites un commentaire !
Leave a comment !

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Tue Mar 31, 2015 6:37 pm
by AAN
1. Etanercept, Adalimumab

2. DLQI becomes increasingly important. We have found, however, that patients starting at high DLQI but low PASI do not often show great improvement in PASI ... this might be because of
a) limited sensitivity of PASI < 10
b) differences in inflammatory kinetics of few chronic localized plaques versus widespread generalized disease
c) exaggerated expectations by patients

In these patients, the PrecisePASI (Kolios et al. Dermatology 2015) might be a good tool to measure improvement. Also DLQI should be followed over time, and expectations managed. After all, a 75% improvement of 'a lot of plaques' results in 'a few plaques', which is satisfactory. But 75% improvement of 'a few plaques' still leaves 'a few plaques', so that treatment situation is a lot more difficult IMO.

3. Agree with IL23, don't agree with 3bis: Pso & cardiovascular risk definitely associated, causality not proven but that is of little clinical relevance.

4 & 5: No comment.

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Tue Mar 31, 2015 6:40 pm
by JHS
I wonder if the members will understand why it is so important that targeting Il23 alone works and how this articulates with the fact that Stelara is presently the top gun on the market
JHS

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Wed Apr 01, 2015 8:10 am
by CFH
"1-Which biologic for psoriasis in childhood ? / Quel biologique donner chez les enfants ?"

At a session at the AAD Meeting, heard the following about treating psoriasis in children:

Pediatric psoriasis: off-label tiny 10mg dosage every 4 days: growth problems (premature closure of the epiphyses)
S002 – Jackson JM et al. Systemic Therapies for Dermatologists: a Comprehensive Review and Update. AAD 2015 Annual Meeting, San Francisco CA – United States

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Wed Apr 01, 2015 8:14 am
by AAN
What drug was given 10mg every 4 days?

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Wed Apr 01, 2015 11:01 am
by CFH
AAN wrote:What drug was given 10mg every 4 days?


Acitretin

Re: (2015-DH4) FOCUS: Psoriasis

PostPosted: Tue Apr 07, 2015 8:42 am
by CFH
JHS wrote:I wonder if the members will understand why it is so important that targeting Il23 alone works and how this articulates with the fact that Stelara is presently the top gun on the market
JHS


I heard there was a Il-23 specific drug called Guselkumab (now in phase II). The following study shows that while specific, it reduced serum Il-17a levels: http://www.ncbi.nlm.nih.gov/pubmed/24679469

Psoriasis Treatment with Guselkumab (specific anti Il-23)

PostPosted: Tue Aug 18, 2015 10:25 am
by CFH
A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis.
Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, Shen YK, Szapary P, Randazzo B, Reich K.
N Engl J Med. 2015 Jul 9;373(2):136-44. doi: 10.1056/NEJMoa1501646.

Psoriasis affects around 2% of the world population
-Treatment depends on the extent of psoriasis and how the patient might adhere to it.
-Treatment options include topical agents, oral medication, phototherapy and injections.
Biologics are the component of this last category. They include Tumor Necrosis Factor (TNF) inhibitors, anti Il-17 and anti-Il-23 antibodies:

TNF inhibitors include adalimumab (A) (Humira, Abbvie) which have been around for a decade
Specific anti Il-23 antibodies include Guselkumab (G)(Janssen-Cilag): it is a fully human IgG1 lambda
monoclonal antibody that inhibits interleukin-23 specific signaling




In this US study published in the NEJM G is compared with A over a 52-week prospective study:



Methods:
293 patients with plaque psoriasis were randomly assigned to 7 groups*:
G 5mg (week 0, 4 and then every 12 weeks)
G 15mg (every 8 weeks)
G 50mg (weeks 0, 4 and then every 12 weeks)
G 100mg every 8 weeks
G 200mg (weeks 0, 4 and then every 12 weeks)
A: 80mg at week 0, 40mg at week one and then every other week
placebo (at 16 weeks, they were put on 100mg gulselkumab)
Evaluation of results:
Physician’s Global Assessment (PGA): score of 0 (clear of lesions) or 1 (minimal psoriasis) (PGA01) at week 16
PASI (Psoriasis Area and Severity Index), PASI 75% improvement (PASI75) and 90% (PASI90)



Results at 16 weeks:
-the proportion of PGA01 was always higher in the G group when compared with placebo (statistically significant) (5mg=34%, 15mg=61%, 50mg=79%, 100mg=86%, 200mg=83%)
-the proportion of PGA01 was higher than A (49%) in the groups treated with G 50mg (71%), 100mg (77%) and 200mg (81%) (no difference was seen for 5 and 15mg)
-Infections were slightly higher in the G treated groups (20%) than A (14%) but the placebo rate was already high at 14%





Comments
The problem with biologics generally speaking is that they tend to become less effective with time (antibodies ?) .Guselkumab (G) seems to offer hope in this regard. Indeed at 40 weeks evaluation:
-The number of patients with a PGA01 with G 100mg remains around 80% (as at 16weeks), whereas for A it falls from 60% to 50%.
Also G works faster than A Indeed for a dose of 100mg of G, the proportion of PSA01 reaches 80% whereas the peak for A is reached at 24 weeks (with a PGA01 of around 75%)
As for PASI one can note that maximum PASI75 improvement is at 20weeks (for G100mg) and reaches almost 95% of treated patients whereas PASI75 is reached in around 70% of individuals (also at 20 weeks)
A has been around a decade (time of publication) and offers an excellent safety profile, but G appears to be more effective…time will reveal its safety profile.





Reminder: Phase 2 studies contrarily to phase 1 studies enable a medication to gather efficacy data (phase 1 studies evaluate safety). This study is funded by by Jansen-Cliag Pharmaceuticals

*subcutaneous injections


CFH