Friday, December 9, 2016

FreitagsGedichte / Kurze Gedichte 09.12.2016



Glück
    in allem
UnGlück
Des
Lebens
Bleibt
Doch noch
Das
    Glück
Zu leben

Visionen
    wenn
Aus den
Visionen
Blut
Fließt
Ist
Jeder
    Traum
AusGeträumt

Strick
    möge
Der
Strick
ZeReißen
Den
Man
Um
Deinen
    Hals
GeLegt hat

TaufSchein
    TaufSchein
HochzeitsUrkunde
Verträge
TotenSchein
Aber
Den
Wichtigen
LebensBerechtigungsSchein
Will man
    Mir nicht
AusStellen

Seele
    wie mag
Die Seele
BeSchaffen
Sein?
Ein Stern
Eine
Kugel
Oder
Gar
    Eine zer-
TreTeNe Amöbe

Jetzt
    in jedem
Jetzt
VerMuten
Wir
Ein Morgen
Aber
Manchmal
Ist da
    Wirklich nur
Ein Jetzt

.

Thursday, December 8, 2016

New Monoclonal Antibodies in Rheumatoid Arthritis




I’ve selected a few MABs, which are possible candidates for the treatment of rheumatoid arthritis with a few additions, which could be more useful in psoriatic arthritis. Even if research has been stopped for some, it might not be that the case is closed permanently. Pharmaceutical firm look at the MABs from an investors point of view, that means research will be directed at the most promising MAB first.

Afasevikumab
Afasevikumab is a human monoclonal IgG1κ antibody targeting IL-17A and IL-17F. There had been a phase 1 trial in “autoimmune disorder”, but this research has been stopped. Nothing on PubMed.
Links:

Bimekizumab (UCB4940)
Bimekizumab (UCB4940) is a monoclonal antibody targeting IL-17A and IL-17F. S. Glatt and colleagues presented a study at the EULAR 2016 meeting in London. In this proof-of-concept-study bimekizumab demonstrated rapid onset and sustained efficacy on disease activity both in skin and joints. Adisinsight reports phase II  studies in ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and rheumatoid arthritis as well as ulcerative colitis.
Links:

Briakinumab
Briakinumab (ABT-874) is a human monoclonal antibody that targets IL-12 and IL-23. Last entry on the drug on this blog had been after the 2012 ACR Annual Meeting, where nothing new had emerged. Further drug development for psoriasis had been stopped in 2011.  There is one phase 2b study however on the possible use of briakinumab in Crohn’s disease.
Links:

Brodalumab
Brodalumab is a human monoclonal antibody targeting the IL-17 receptor and inhibits the binding of several types of IL-17 to the receptor. The Dermatologic and Ophthalmic Drugs Advisory Committee to the FDA has voted for the approval of brodalumab for adult patients with moderate-to-severe plaque psoriasis (July 2016) despite safety concerns (suicides). I have already mentioned the problem in a blogpost on Apremilast. Nothing on arthritis studies at both the 2016 EULAR and ACR Annual Meetings.
Links:

Clazakizumab (ALD518)
Clazakizumab (formerly ALD518) is a humanized monoclonal antibody against IL-6. I had written about Clazakizumab after the EULAR 2014 Annual Meeting in Paris. I haven’t seen any new study at both the 2016 EULAR and ACR Annual Meetings.  
There had been a study in 2015 by M.E. Weinblatt and colleagues that showed treatment with clazakizumab in combination with methotrexate or clazakizumab monotherapy in patients with rheumatoid arthritis was well tolerated, and patients achieved significant improvements in disease activity with higher rates of remission.
P.J. Mease and colleagues published a study on clazakizumab in patients with psoriatic arthritis. They concluded: “This is the first clinical trial of an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment option for musculoskeletal aspects of PsA, but because of the lack of a dose response in this study, further studies are required to confirm the appropriate dose.” The study doesn’t make me as enthusiastic as the authors. Maybe TNF-alpha is a much better target in psoriatc arthritis that IL-6.
In May 2016 “Alder BioPharmaceuticals has licensed exclusive worldwide rights to its Phase II inflammation candidate clazakizumab”.
Summing it up, clazakizumab might be a candidate, but approval as a drug is still a far goal.
Links:

Clenoliximab
Clenoliximab is a monoclonal antibody against CD4, which has been investigated for the treatment of rheumatoid arthritis. There had been a study by T.W. Hepburn in 2003 with the conclusion: “Decrease in the density of CD4 on the T-lymphocyte surface is caused by antibody-mediated stripping.” As no other study has been published afterwards, we may well assume, that clenoliximab is history in the treatment of rheumatoid arthritis.
Links:

Fezakinumab
Fezakinumab is a human monoclonal antibody targeting IL-22.  Adinsight reports discontinuation of studies in psoriasis in 2011. I haven’t seen any new study at both the 2016 EULAR and ACR Annual Meetings. So I guess, we won’t see more of fezakinumab in rheumatology.
Links:

Fletikumab
Fletikumab is a monoclonal antibody targetting IL-20 for the treatment of rheumatoid arthritis. Careful, it’s IL-20 and not CD20. As IL-20 plays a role in keratinocytes during inflammation, one should think more of a possible usefulness in treating psoriatic arthritis, or even more in placque psoriasis, than rheumatoid arthritis. Nevertheless there had been phase 2 studies in rheumatoid arthritis patients, which had been discontinued in September 2014. There haven’t been any new studies at both the 2016 EULAR and ACR Annual Meetings. Dead end?
Links:

Ixekizumab
Ixekizumab is a humanized monoclonal antibody, which targets IL-17A and is also known as LY2439821. I’ve written already about ixekizumab several times, especially after 2013 EULAR Annual Meeting in Paris. P.J. Mease and colleagues presented a study at the 2016 EULAR Annual Meeting (SPIRIT-P1). They looked at 304 patients with psoriatic arthritis. The authors concluded: “IXE [Ixekizumab] demonstrated clinically significant improvement in signs and symptoms of PsA including arthritis, dactylitis and enthesitis as well as skin manifestations across treatment groups in the EP [Extension Period].” More studies were presented, like effect on work productivity, quality of life and so on. There have been even more studies at the 2016 ACR Annual Meeting. FDA and EMA approved Taltz (ixekizumab) to treat adults with moderate-to-severe plaque psoriasis. This and the commitment to studies on psoriatic arthritis will most probably lead to the approval of Taltz for rheumatologic indications in the future.
Links:
DOI: 10.1136/annrheumdis-2016-eular.1172

Lulizumab pegol (BMS-931699)
Lulizumab pegol is a monoclonal antibody, which targets CD28. Maybe you remember another MAB targeting CD28 -: TGN1412, which caused multiple organ failure. “CD28 has also been found to stimulate eosinophil granulocytes where its ligation with anti-CD28 leads to the release of IL-2, IL4, IL-13 and IFN-γ.” But it seems that lulizumab is past this point of concern. At the moment phase 2 studies in patients with Sjogren’s syndrome are under way. A study in systemic lupus erythematodes is still recruiting patients. There haven’t been any studies presented at both the 2016 EULAR and ACR Annual Meetings.
Links:


This list will be completed over the next few months.

And don’t miss Wikipedia’s „List of therapeutic monoclonal antibodies”, which lists about a zillion MABs - https://en.wikipedia.org/wiki/List_of_therapeutic_monoclonal_antibodies.







Started: 08.12.2016
New entries: 09.12.2016 /