Friday, June 23, 2017

Iguratimod at the 2017 EULAR Annual Meeting in Madrid



I’ve been following the development of iguratimod very closely since 2012 [1]. Iguratimod is a disease modifying anti-rheumatic drug (DMARD); chemical formula: N-(3-Formamido-4-oxo-6-phenoxy-4H-chromen-7-yl)-methanesulfonamide. “Iguratimod is characterized by inhibitory effects on immunoglobulin production in B cells as well as inhibiting cytokine production. Its' mode of action comes by suppression of nuclear factor kappa B (NF-kB) activation.” It is approved for the treatment of rheumatoid arthritis in Japan as well as in China![2]

There had been four abstracts on iguratimod at the 2017 EULAR Annual Meeting in Madrid.

K. Tokunaga and colleagues looked at [3]: “COMPARISON OF EFFICACY BETWEEN COMBINATION THERAPY WITH IGURATIMOD [IGU] AND SULFASALAZINE [SSZ] WITH METHOTREXATE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS: PROPENSITY SCORE ANALYSIS”. Luckily the study excluded DMARDs like tacrolimus and bucillamine, which aren’t approved worldwide for rheumatoid arthritis. In results we read: “The remission rates of DAS28-CRP in the following year was 77.2% (44/57 patients) and 71.7% (38/53 patients; P=0.52) in the IGU and SSZ groups, respectively.” Conclusions: “Combination therapy with IGU or SSZ and methotrexate for rheumatoid arthritis did not show a significant difference in disease activity. Further studies are needed.“ According to this study iguratimod fits into the group of csDMARDs like methotrexate, leflunomide, sulfasalazine, azathioprine.

Y. Hirano and colleagues presented [4]: “LONG-TERM OUTCOME OF IGURATIMOD, CONVENTIONAL SYNTHETIC DISEASE-MODIFYNG ANTI-RHEUMATIC DRUD DEVELOPED IN JAPAN, IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD CLINICAL SETTING”. “82% of patients had factors influencing to prescribing IGU and intolerance of dose escalation of MTX was 1st reason (23.3%), old age over 80 years old was 2nd reason (16.7%) and economical reason was 3rd (14.2%)”. In conclusions the authors hinted t: “Although biological DMARDs is effective in RA patients, the cost is very expensive. IGU is comparative cheap (¥9,200/month) and suitable for RA patients with economical difficulties.” ¥9,200 is a little less than 75 €.

T. Suto and colleagues also presented long term data [5]: “EFFICACY AT THREE YEARS OF DAILY CLINICAL USE OF IGURATIMOD IN PATIENTS WITH RHEUMATOID ARTHRITIS”. “The survival rate at 3 years was 49.3%, and 8 patients discontinued the IGU therapies due to insufficient response, 12 patients due to adverse events such as exanthema, pneumonitis or hepatic disorder, and other patients based on their requests.” Conclusions: “We assessed middle-term outcome of the clinical use of iguratimod therapy in RA patients. The low DAS28-CRP and low usage rate of prednisolone at the initiation of IGU were significant factors of clinical remission achievement at 3 years.”

Iguratimod could be a useful addition to existing csDMARDs, but would have to be evaluated in randomized controlled studies. Maybe a pharmaceutical firm in Europe or the US should buy the patent for the non-Asian market and evaluate iguratimod in studies that are needed to get EMA or FDA approval. Otherwise only Japanese and Chinese patients will have access to iguratimod.


Links and References:
[3] DOI: 10.1136/annrheumdis-2017-eular.6157
[4] DOI: 10.1136/annrheumdis-2017-eular.4852
[5] DOI: 10.1136/annrheumdis-2017-eular.6040

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Friday Poems / ShortPoems 23.06.2017 / 23.12.2016





Hell
    Where do
You
Look
For
Hell?
Deep
Below
Yourself?
Deep
Below
It may
Well be
Beneath
    The abysses
Of your soul

Notes
    Certainly
You
May
Also
Take
Notes
On the smartphone
But
Yet
It is
    Not a
Notebook

Underground
    Underground
Is
A
Foretaste
As
How
It
May be
    Below
Ground

Estuary
    The
Achievement
Of
The river
Is
The estuary
And
There
    He dies
After all

Auschwitz
    One does
Not
Know
All
The names
Of the
Murderers
But
None
Wearing
The
Mark of Cain
    On the
Forehead

Heaven
    Just
Because
We are
So
Small
We
Will
Always
Try
    To touch
The sky
                        Sky and heaven are both Himmel in German

Executioner
    The hangman
Had
Certainly
Been
Touched
As
The
Delinquent
Shook hands
With him
    And
Smiled


Link to original German version:

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Dekavil at the 2017 EULAR Annual Meeting in Madrid




Dekavil (F8-IL10) is a fully human immunocytokine, composed of the antibody fragment F8 fused to the anti-inflammatory cytokine interleukin-10 (IL-10). I’ve come across dekavil for the first during the 2012 EULAR Annual Meeting in Berlin [1]. I’ve been quite mad after the 2013 EULAR Annual Meeting in Madrid [2]: “Please promise to publish more than promising data at the ACR 2013 at the next ACR meeting.”

M. Galeazzi and colleagues published a phase 2 study [3] titled: “SAFETY, TOLERABILITY AND INITIAL SIGNS OF EFFICACY OF THE FULLY HUMAN IMMUNOCYTOKINE DEKAVIL (F8IL10): A NOVEL THERAPEUTIC APPROACH FOR RHEUMATOID ARTHRITIS”. The abstract is difficult to read as it also looks at data from a phase 1b study. “As of January 2017, 22 out of 87 patients have been treated in the phase 2 clinical study and neither SUSAR [Suspected Unexpected Serious Adverse Reaction] nor treatment-related deaths were recorded.” Conclusions: “The currently available data suggest that Dekavil is a safe and promising novel therapeutic for the treatments of RA.” I don’t see such a conclusion. And yeah, there we are again – promising.

Adisinsight reports termination of a phase 1 trial in Inflammation (in volunteers) in the US in2016 and of a phase 2 clinical trials in rheumatoid arthritis in Italy in 2014 [4].
On the other hand this study “A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX” is marked as “is currently recruiting participants” in Clinical Trials [5].

It’s hard to share the enthusiasm of the authors. The idea of getting IL-10 to where inflammation is raging is wonderful. I don’t want to sound like a merchant of doom, but I have my doubts about dekavil.


Links and References:
[3] DOI: 10.1136/annrheumdis-2015-eular.3889

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Arztverzeichnis Regional




Gestern wurde mir ein Fax vorgelegt. Es ist ähnlich gestaltet, wie das für den Eintrag ins Regionale Ärztebuch, über das ich vor etwa vier Jahren berichtet hatte [1]. Also habe ich mich zum Arztverzeichnis Regional erst einmal informiert.


Man stolpert über den Namen des Verzeichnisses – Arztverzeichnis. Es sollte doch ein Ärzteverzeichnis sein. Aber ich wurde eines Besseren belehrt. Unter den Suchbegriffen Arzt und Meerbusch fand ich auch wirklich nur eine Ärztin. Ist dieses Verzeichnis nun so exklusiv und damit überflüssig, oder aber zeigt es nur an, dass bisher in Meerbusch nur eine Ärztin auf den Trick hereingefallen ist.

Wenn man die Allgemeinen Geschäftsbedingungen liest [2], dann ist dort von einem „Kostenlosen Standarteintrag“ die Rede – sehen wir einmal davon ab, dass man Standard mit d schreibt. Aber dieser Standardeintrag ist völlig egal, denn mit dem Fax hat man einen Vertrag für den „Kostenpflichtigen Grundeintrag“ geschlossen. Wenn Sie später einmal den Vertrag anfechten wollen, wünsche ich gute Reise, denn: „Für alle Ansprüche der Parteien wird als Erfüllungsort und Gerichtsstand Bukarest vereinbart, …“.


Und nun suchen Sie einmal das Arztverzeichnis Nordrhein-Westfalen unter Google. Was? Nicht gefunden?! Das Landgericht Wuppertal urteilte darüber (Beschluss v. 05.06.2014 - Az.: 9 S 40/14): „Ein kostenpflichtiger Eintrag in ein Online-Verzeichnis, das bei Google nicht unter den ersten fünf Suchtreffern gelistet ist, ist wertlos und erfüllt den Tatbestand der Sittenwidrigkeit.“ [3]

Was machen Sie nun mit dem Fax? Archivieren Sie es im Schredder!


Links:

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