Ustekinumab at the EULAR 2013 Meeting

Ustekinumab (Stelara) is a human monoclonal antibody against IL-12 and IL-23. Adverse events include an increased risk of infections (tuberculosis and others) and cancer. There were a couple of studies on Ustekinumab and I've been eager to know, whether these studies confirmed the positive impressions, the drug had made last year. I didn’t see the solution of problems treating psoriatic arthritis in ustekinumab, but thought of getting a new option to treat at least some patients with psoriatic arthritis better than before (ACR 2012). Now let’s switch to the newer studies or new results.

P. Rahman an colleagues presented a study [SAT0264]: "Ustekinumab [UST] improves physical function, quality of life and work productivity of patients with active psoriatic arthritis who were naïve to MTX, despite MTX therapy or previously treated with anti-TNFα: results from PSUMMIT I and PSUMMIT II". Conclusions: "UST improves physical function, improves general, arthritis and skin-related quality of life, and reduces the impact of disease on work productivity in patients with active PsA regardless of current or prior MTX use or prior anti-TNF experience." If you expected differences in patients naïve to anti-TNFα, your're right. In results we find: " In the anti-TNF naïve population, statistically significantly greater improvement in SF-36 MCS was observed in the combined UST 45mg and 90mg group vs PBO."

I. McInnes and colleagues presented [SAT0267]: "Safety of ustekinumab from the placebocontrolled periods of psoriatic arthritis and psoriasis clinical developmental programs". The conclusions as expected: " During the PBO-controlled portion, UST was well-tolerated. Overall safety were consistent between populations & safety event rates were generally comparable between pts receiving PBO & UST within each population."

K. Papp and colleagues looked at long-term safety [SAT0287]: "Long-term safety of ustekinumab: 5 years of follow-up from the psoriasis clinical development program including patients with psoriatic arthritis". Conclusions: "With continuous UST exposure for up to 5yrs and approximately 9000 pt-years of follow-up in the PsO development program, long-term safety in the Overall Population were consistent with previous reports at earlier follow-up and event rates were generally comparable to other currently approved biologic agents. Long-term safety in the sub-group of PsO patients with a history of PsA at baseline were generally comparable to those in the overall study population." Nothing unexpected, but this look on safety makes one feel safe to prescribe the drug later.

C. Ritchlin and colleagues presented the following study [OP0001]: "Maintenance of efficacy and safety of ustekinumab in patients with active psoriatic arthritis despite prior conventional nonbiologic and anti-TNF biologic therapy: 1 yr results of the PSUMMIT 2 trial". The highest ACR70 was reached in the 90 mgs group at 17.9%. Conclusions: "Both UST doses (45/90 mg q12w) yielded significant and sustained improvements in PsA signs/symptoms with favorable and comparable safety profiles. UST was effective in both anti-TNF-naïve and anti-TNF-experienced pts, with greater efficacy in anti-TNF naïve pts and anti-TNFexperienced pts previously treated with 1 or 2 anti-TNF agents."

It seems we're getting a new drug to treat psoriatic arthritis - now let's wait for if and when FDA and EMEA approve ustekinumab.


Link:
ACR 2012 in Washington http://rheumatologe.blogspot.de/2012/12/ustekinumab-at-acr-2012-in-washington.html

Abnehmen mit Bodyformpill?

Ich sehe eine Anzeige zur Bodyformpill, also der Körperformpille. Wer sich der Illusion hingibt, mit Pillen oder besser Kapseln, denn bei der Bodyformpill handelt es sich um eine Kapsel und nicht um eine Pille, das Gewicht reduzieren zu können, wird schnell feststellen, dass sich eher der Inhalt des Geldbeutels als das Gewicht reduziert.

Die Anzeige klärt uns auf, dass die EFSA die europäische Behörde für Lebensmittelsicherheit ist. Also ein Allgemeinplatz, der nichts mit dem Produkt zu tun hat. Link: http://www.efsa.europa.eu/de/topics/topic/nutrition.htm
Dann fährt der Anzeigentext fort: “Unsere neue Kapsel Bodyformpill enthält gelistete Inhaltsstoffe.” Was ist das Besondere daran? Das Besondere ist, dass man mit dem nächsten Allgemeinplatz wirbt. Jedes Nahrungsergänzungsmittel besteht aus gelisteten Inhaltsstoffen, denn so schreibt es das Lebensmittelrecht vor. Gehen Sie in den nächsten Supermarkt und greifen Sie wahllos nach einem Nahrungsergänzungsmittel und es besteht aus gelisteten Inhaltsstoffen.
„Breaking news“ wird die Werbung überschrieben, aber dann sind es nicht amerikanische sondern französische Forscher, die eine Spezialmischung entdeckten. Schauen wir einmal auf die Inhaltsstoffe.

Chrom:
Zu Chrom gibt es drei Studien; Links siehe unten. Eine polnische Studie beschäftigt sich mit dem Nachweis von Inhaltsstoffen. Eine russische Studie untersuchte eine anti-atherosklerotische Diät mit Inhaltsstoffen. Eine österreichische Studie kam zu dem Ergebnis, dass eine Gewichtsabnahme nicht von Chrom abhängig ist (die Gewichtsreduktion unter Placebo war genau groß); allerdings fand sich für Chrompicolinat, nicht für Chrom aus Hefe, langfristig eine stärkere Zunahme an Muskelmasse.

Zink:
Zu Zink lassen sich deutlich mehr Studien finden, aber es findet sich kein Hinweis darauf, dass durch die Einnahme von Zink die Gewichtsreduktion gefördert werden kann. Nach einer spanischen Studie, und das ist die neueste Studie (2007), erniedrigt sich der Zinkspiegel nicht signifikant während der beobachteten Diätphase, so dass sich eine Substitution auch nicht lohnt.

Artischockenblatt-Extrakt:
Zu Artischocke (Cynara scolymus) und Gewichtsreduktion schweigt sich PubMed aus – und das ist die größte Datenbank der Welt zu wissenschaftlichen Veröffentlichungen im Bereich Medizin.

Guarana:
Auch Guarana gibt es keine gesicherten Erkenntnisse zu Gewichtsreduktion. Ein interessanter Hinweis findet sich in der Untersuchung von McLellan und Kollegen: „With the exception of some weak evidence for glucose and guaraná extract, there is an overwhelming lack of evidence to substantiate claims that components of EDs, other than caffeine, contribute to the enhancement of physical or cognitive performance.” D.h. Guarana könnte einen leicht stimulierenden Einfluss auf den Stoffwechsel haben, mehr aber auch nicht. Da wären Sie mit einer Tasse Kaffee besser bedient.

Nopalblatt-Extrakt:
Ich gebe zu, vom Nopalblatt noch nie gehört zu haben. Also habe ich mich schlau gemacht. Zunächst über Wikipedia. Aha, es handelt sich also um Opuntien; vielleicht haben Sie schon einmal Kaktusfeigen gegessen, sehr schmackhaft und über die Farbstoffe auch reich an Antioxidantien, aber das fällt bei einem Blattextrakt natürlich weg. PubMed hat auch zu diesem Thema nichts. Der Werbetext erklärt uns, dass die Gewichtsreduktion durch die Absorption von Fett und Zucker zustande kommt. Aber hallo! Wieviel Fett soll denn so eine Kapsel absorbieren? Das ist pures Wunschdenken.

Die reduzierte 90-Tage-Packung soll 119,40 € kosten. „Sie sparen € 30,-“. Hier hört der Spaß für mich auf. Das rangiert bei mir als Abzocke und davon rate ich ab. Da sparen Sie direkt 119,40 € im Quartal.

Links:
Chrom / polnische Studie: http://www.ncbi.nlm.nih.gov/pubmed/21980860  
Chrom / russische Studie: http://www.ncbi.nlm.nih.gov/pubmed/10943006  
Chrom / österreichische Studie: http://www.ncbi.nlm.nih.gov/pubmed/9480618  
Zink / spanische Studie: http://www.ncbi.nlm.nih.gov/pubmed/18271402  
Guanara / McLellan: http://www.ncbi.nlm.nih.gov/pubmed/23206286  
Nopalblatt / Wikipedia: http://de.wikipedia.org/wiki/Nopalea  

Plaste und Elaste

Gestern postete ich auf Twitter den folgenden Tweet:

Anlass war die schrille Farbe der Krawatte von Bundesminister Peter Altmaier. Ich dachte an Plastik und weiter an Plaste und Elaste, da die Werbung der Buna-Werke („Plaste und Elaste aus Schkopau“) für mich ein wichtiger Punkt nach Berlin auf der Rückreise mit dem Auto durch die DDR gewesen ist. Als Jugendliche fanden wir den Ortsnamen schon komisch genug und nun kam noch die DDR Bezeichnung für Plastik dazu. Ich meine aber, wir sollten solche Spracheigenheiten bewahren.

Als ich heute den Tweet als Retweet nochmals lese, kommen mir noch ganz andere Assoziationen. Ich ging durch Punta Arenas in Chile, auf dem Weg zur Fähre nach Feuerland, und kam am Casa del Plastico vorbei. Dort bot man Plastikwaren feil. Und auf dem Gehsteig war jemand damit beschäftigt, das Gras zwischen den Platten mit Chlorbleiche zu entfernen. Ah, dachte ich, kein Grashalm ist erlaubt vor dem Haus für Plastik.

Gestern auf dem Rastplatz

Gestern war ich auf der Heimfahrt abends noch auf dem Rastplatz Stindertal (A3). Zuerst dachte ich, es sei eine Katze, aber als ich näher herankam, sah ich, dass es sich um ein ziemlich großes Kaninchen handelt mit einer Fellfärbung, die in der freien Natur so nicht zu sehen ist. Bevor ich mich noch wundern konnte, warum das Kaninchen nicht weglief, hoppelte ein schneeweißes Kaninchen, etwas kleiner, heran. Die beiden sind also ausgesetzt worden. Was denken sich diese „Tierfreunde“ dabei? Wie lange sollen denn Heimtiere in der freien Wildbahn überleben? Strafbar ist es übrigens auch. Das Tierschutzgesetz verbietet das Aussetzen von Tieren. Die Strafe geht bis 25.000 €. Ich würde so etwas anzeigen.

Eine Initiative gegen das Aussetzen von Tieren: http://www.forum.kaninchen-at-home.com/pages/aktion/aktion.html  

Nachtrag 27.06.2013
Ich hatte mich gestern an die Polizei gewendet, aber die meinten, dass die Kreisverwaltung Mettmann zuständig wäre. Von dort kam auch eine freundliche und informative Email, dass das Ordnungsamt der zuständigen Stadt eingeschaltet werden müßte. Gestern Abend habe ich die beiden schon nicht mehr gesehen. Ich werde aber heute noch einmal am Rastplatz vorbeifahren und nachschauen.

Nachtrag 01.07.2013
Schon am Tag nach dem ich die beiden gesehen hatte, waren sie nicht mehr zu sehen. Ich habe einige interessante Gespräche geführt, z.B. mit Dr. Kruse vom Amt für Verbraucherschutz (Stellvertretender Amtstierarzt), bei dem ich mich herzlich bedanken möchte.
Ein Rastplatz oder die Umgebung kann Anlass zu einer Zuständigkeitsproblematik geben. Sollte ich nochmals so etwas erleben, würde ich bei der Autobahn-Polizei nicht so schnell aufgeben. Bis ein Ordnungsamt verständig ist, das sowieso in diesem Bereich nicht offiziell tätig werden kann, vergeht wahrscheinlich doch zu viel Zeit, so dass ich mich an Tierschützer wenden würde.

VX-509 at the EULAR 2013 Meeting

No, VX-509 isn’t a motor oil, it’s a JAK3 inhibitor. There hadn’t been much at the EULAR 2012 Meeting and nothing at the ACR 2012 Meeting. Link. http://rheumatologe.blogspot.de/2012/07/vx-509-and-eular-2012.html. But VX-509 was sighted again at the EULAR 2013 Meeting.

I. M. Catlett and colleagues presented [THU0160]: “The effect of VX-509, a selective oral JAK3 inhibitor, on plasma biomarkers of disease activity in patients with rheumatoid arthritis.” Conclusions: “VX-509 treatment modulated biomarkers of RA associated with inflammation (IL-6, CD25, and CCL18) and bone erosion (MMP-3). These changes are consistent with the efficacy of VX-509 in improving RA signs and symptoms.” – and then I had a strange feeling … I accessed: http://www.abstracts2view.com/eular/view.php?nu=EULAR13L_THU0160 … and I found the same abstract in the archives of EULAR 2012!

We should ask Vertex if they still want to bring VX-509 to the market. Maybe they should change the motor oil name into a pharmaceutical name. Or maybe it’s also bye-bye VX-509.

Secukinumab at the EULAR 2013 Meeting

I’ve already written on secukinumab: http://rheumatologe.blogspot.de/2013/06/targeting-interleukin-17-in-patients.html. Here’s more on this drug.

X. Baraliakos and colleagues presented [FRI0420]: “Long term inhibition of IL-17a with secukinumab reduces spinal inflammation but has no influence on fatty lesions as assessed by magnetic resonance imaging in patients with ankylosing spondylitis.” Quo usque tandem abutere, Catilina, patientia nostra? No, that’s a bit too hard, but it’s the same study as presented in Washington.

O.K. We’ve still got another study. U. Klein and colleagues presented [SAT0142]: “Immunogenicity of the novel anti-IL-17a antibody, secukinumab, with intravenous and subcutaneous dosing regimens in healthy subjects and patients.” Conclusions: “Based on the available data, secukinumab appears to carry a low risk of immunogenicity. In the very few transient immunogenicity positive patients identified so far, there has been no indication of altered pharmacokinetics or loss of efficacy, and no adverse event that could be linked to immunogenicity has been detected. More data from the ongoing phase 3 studies are required to strengthen this encouraging finding in a larger patient population.”

The more I read on secukinumab the surer I get. We won’t here much on RA and secukinumab.

Tabalumab at the EULAR 2013 Meeting

I had been disappointed about tabalumab at the ACR 2012 Meeting. Even as there had been four studies in Washington. The reasons for my disappointment are here: http://rheumatologe.blogspot.de/2012/12/tabalumab-at-acr-2012-in-washington.html How about Madrid?

E. R. Dow and colleagues presented [SAT0005]: “Human C-type lectin domain family 4, member C gene expression level helps predict future clinical response to tabalumab blockade of BAFF in rheumatoid arthritis”. In German we have the idiom “BAFF erstaunt sein”, which means to be flabbergasted. That’s describes my feelings. Only one study at the EULAR and … it’s an abstract, which had already been presented at the ACR 2012 Meeting.

Bye bye tabalumab.

Carpe diem Haiku Gion Festival

Don't want to paint black

Girls dressed in their yukata

May a soft breeze blow

Ancient rituals

Festival foods to partake

Happy crowds moving

Carrying the floats

Sounding the big temple bell

The clouds won't bring rain

Little samurai

So earnest at his young age

Ready for the cut

With a single blow

Matsuri is starting now

Auspicious omen

http://chevrefeuillescarpediem.blogspot.de/

Iguratimod at the EULAR 2013

Allow me to quote myself from last year: "Iguratimod (T-614) is a novel disease modifying anti-rheumatic drug (DMARD). 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." Please look for the link below. Last year there had been three studies, this year only one. My evaluation last year: "I think iguratimod is indeed a promising candidate for treatment of active rheumatoid arthritis and might become a needed alternative in the conventional (traditional) DMARD class."

The study this year on iguratimod is surprisingly by a Chinese group; W. Tan and colleagues presented: [AB0110]: "Iguratimod inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells". Conclusions: "These results indicate that iguratimod is a potent inhibitor of osteoclastogenesis, supporting its therapeutic benefit for preventing bone erosion in RA." No matter how important these findings are, I had expected some clinical study this year.

Japanese and also Chinese rheumatology is different to the West as there are some DMARDs approved, we don't have here. Japan has Tacrolimus, Bucillamine, and Mizoribine for instance. So not publishing here might not mean that the drug has been abandoned. I hope for a study at the ACR 2013.

Link: http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

Drugs that didn't show up at the EULAR 2013 Meeting in Madrid

Prior to the EULAR 2013 Meeting in Madrid I had published my list of topics, I'm interested in. I was just going through my list and found out that there are a lot of drugs that didn't have any publication at the EULAR 2013. It may mean that these drugs won't be studied anymore because the drug companies don't see any profit. But this can't be 100%, maybe some drugs need more time for the next publications.

ARRY-371797 / ARRY-797
Nothing!
Link for last ACR meeting: http://rheumatologe.blogspot.de/2012/12/arry-797-at-acr2012-in-washington.html

BT061
Nothing!
Estimated Study Completion Date: December 2013. http://clinicaltrials.gov/ct2/show/NCT01481493 So, unless there is some other information we should wait until the ACR2014.

CCX354-C
Nothing!
I'm not expecting too much in the furture.
For EULAR 2012 look at: http://rheumatologe.blogspot.de/2012/07/ccx-354-c-at-eular-2012.html

Cetrorelix
Nothing!
I have already had my reservations against this gonadotropin-releasing hormone antagonist (GnRH antagonist): http://rheumatologe.blogspot.de/2012/07/cetrorelix-at-eular-2012.html http://rheumatologe.blogspot.de/2012/12/cetrorelix-at-acr-2012-in-washington.html  

MOR103
Nothing!
After the stunt with the late breaking poster at the ACR 2013 this is disappointing, but I'd thought that the paper left open lots of questions.
Link: http://rheumatologe.blogspot.de/2012/12/mor103-at-acr-2012-in-washington.html  

NKG2a
Nothing!
Links to the previous meetings, if you're still interested: http://rheumatologe.blogspot.de/2012/07/nkg2a-nnc141-0100-at-eular-2012.html and http://rheumatologe.blogspot.de/2012/12/nkg2a-at-acr-2012-in-washington.html  

NNC0114-0005
Nothing!
NNC0114-0005 is a recombinant anti-IL-21 monoclonal antibody. I had my doubts, as one paper ended in the conclusion: "The improvements in DAS28-CRP for patients with RA at the highest dose level may suggest biologic and clinical activity of NNC0114-0005." Link: http://rheumatologe.blogspot.de/2012/12/nnc0114-0005-at-acr-2012-in-washington.html  

Ocaratuzumab
Nothing!
As ocaratuzumab showed rapid and sustained depletion of circulating B-cells in rheumatoid arthritis patients, I was surprised. Link to more information: http://rheumatologe.blogspot.de/2012/12/ocaratuzumab-at-acr-2012-in-washington.html  

Ocrelizumab
Nothing!
I didn't expect to hear more from this anti-CD20 MAB.
Link: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html  

Olokizumab
Nothing!
Very strange as olokizumab targets interleukin-6 (IL-6). Link to more information from the ACR 2012: http://rheumatologe.blogspot.de/2012/12/olokizumab-at-acr-2012-in-washington.html  
Postponed or abandoned?

Ozoralizumab (ATN-103)
Nothing!
It had been presented as "a trivalent, bispecific nanobody that potently neutralises TNF". Link: http://rheumatologe.blogspot.de/2012/12/ozoralizumab-atn-103-at-acr-2012-in.html
If I hear nano, I think of hype; an if new drugs don't show up at the next meeting, it makes me even more skeptical.

Pioglitazone
Nothing!
Doesn't come as a surprise, please look here:
http://rheumatologe.blogspot.de/2012/12/pioglitazone-at-acr-2012-in-washington.html 

PRTX-100 (Staphylococcal Protein A)
Nothing!
As I had been part in testing immunoadsorption, I´m not too confident in PRTX-100. But it´s still early for skepticism.You find more here: http://rheumatologe.blogspot.de/2012/12/prtx-100-staphylococcal-protein-a.html
I thought that he EULAR 2013 might still be too early. So I'll be watching, if something comes to surface at the ACR 2013.

SBI-087
Nothing!
SBI-087 is a SMIP (= small molecule immune pharmaceutical) binding to CD-20 http://rheumatologe.blogspot.de/2012/07/sbi-087-at-eular-2012.html  
Guess it's abandoned.

Synavive
Nothing!
Synavive, a combination of 2 mgs of prednisolone and 200 mgs of dipyramidole: http://rheumatologe.blogspot.de/2012/07/synavive-crx-102-at-eular-2012.html.
Should be abandoned.

Veltuzumab
Nothing!
Please check: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html  
A year without results? Better forget this drug.

VX-702
Nothing!
There hasn't been anything new on VX-702, a novel p38 MAPK inhibitor, since 2011. My guess: p38 MAPK inhibitors don't work.

Modified Release Prednisone at the EULAR 2013

I have already published my concerns about modified release prednisone severeal times; please look for the links below.

At the EULAR 2012 Meeting there had been four studies: "To sum up these studies: Lodotra (modified-release prednisone) failed to show a clear advantage over conventional immediate-release prednisone in the studies presented at the 2012 EULAR meeting. One study failed to look at 1733 of 2661 patients, while another study only presented data on 950 of 1928 patients."

At the EULAR 2013 Meeting we could see two studies on modified release prednisone.

M. Benucci and colleagues presented [SAT0152]: "Polymyalgia rheumatica: a comparative study of methylprednisolone and the modified release prednisone". The study is non-blinded, non-randomized and looks only at N=42 in two groups. The endpoint is unclear. The objective is to " compare changes in inflammation markers and their correlations with cortisol levels ...". Conclusions: " In this non-randomized prospective observational study the response of inflammation markers to low-dose GC was similar in patients with PM treated with 6-MP or MR-P, and morning cortisol levels were unaffected. However, the patients treated with MR-P showed a greater decrease in IL-6 levels after the first month."
Does anyone treat IL-6 levels after the first month in patients with polymyalgia rheumatica? I don't! So this study rather convinces me to not use Lodotra.

D. Sola and colleagues presented a study [AB0346]: "Safety and efficacy of rheumatoid arthritis treatment with modified-release prednisone (MR-PDN), experience in “real life”". The study is retrospective! Objectives: "To assess in “real life” adherence to treatment and efficacy (morning stiffness, DAS28 score and steroid dose reduction) in RA patients who initiated treatment with MR-PDN,". "64 RA patients who initiated RM-PDN completed a 12 weeks (W) follow-up, 49 completed 24 W and 33 48W." So the study lost about 50% of it's initial patients to follow up after 48 weeks or is incomplete. "In 19 patients this was the first steroid treatment, 45 received MR-PDN after a switch from one other steroid (in this case 1 month bridging with traditional steroid was performed)." So, in about 33% of the patients we look at prednisone naive and in 66% at pretreated patients. At week 48 only 64% stayed on treatment. "The efficacy analysis was limited only to patients with DMARDs or biological therapies stable for the whole period of observation." But we don't know how many patients had been on which therapy. And in the end we look at patients, who have been doing better and measure the success. Conclusions: "In RA patients in “real life” the use of MR-PDN showed good safety profile and adherence to treatment also after switch from prolonged traditional steroid treatment. We observed a reduction in morning stiffness and disease activity similarly to that described in clinical trial. The greatest improvement occurs within the first 12 weeks confirmed by further modest improvement up to 48 weeks. Finally the use of the MR-PDN permitted a lower consumption of steroid in these patients with obvious long term benefits."
The study is a catastrophe. It looks retrospectively at a heterogenous group of patients (pretreated with steroids of steroid naive, on traditional DMARDs or on different biologics) without a well defined endpoint. Is it desirable to stay on prednisone after 48 weeks? Is the reduction of morning stiffness and disease activity due to modified release prednisone or DMARDs/biologics? What is the idea of the authors behind: lower consumption of steroid? Lower than at the beginning? That would mean modified release prednisone could be tapered like any other steroid. What are the "obvious long term benefits"?

These two studies convince me even more that modified release prednisone (Lodotra) won't be my drug of choice.

Links:
http://rheumatologe.blogspot.de/2012/11/lodotra-auf-dem-kongress-der.html (Text in German)
http://rheumatologe.blogspot.de/2012/06/modified-release-prednisone.html
http://rheumatologe.blogspot.de/2010/06/lodotra-my-problems-with-new-miracle.html

Mikrochip-Hörhilfe

Ich wollte schon drüber hinweglesen, da ich schließlich kein HNO-Arzt bin, aber dann sah ich die Aufmachung der Anzeige und dachte, dahinter kann nur eine Abzockemasche stecken. Link: http://www.horizont.net/kreation/pages/pics/original/print242704.jpg Es geht um die Mikrochip-Hörhilfe.

"Mikrochip-Technik als Geheimnis" - das klingt so überzeugend modern und wirkt darüber hinaus wie ein Alleinstellungmerkmal, aber das ist es nicht. Jedes Hörgerät hat das auch und sicher noch besser und ausgefuchster. Besonders das Wort Geheimnis soll verschleiern.
Das Gerät sieht aus wie ein schlecht gemachtes Hörgerät und das wird es auch sein. Es besteht aus einem Mikrofon, dem Akku- und Mikrochip-Teil und dann kommt der Ausgabeteil mit ... Ohrstöpsel. Es werden fünf Ohrstöpsel mitgeliefert. Es handelt sich also um nicht individuell angepaßte Teile. Gerade dieser Teil ist aber wichtig für den Tragekomfort. Dann ist da noch ein USB-Anschluss "zum wieder aufladen". Moderne Hörgeräte erlauben eine Einstellung der verschiedenen Frequenzen, denn die sind bei Schwerhörigkeit nicht gleichmäßig betroffen. Die Mikrochip-Hörhilfe verstärkt einfach alles. Aber über solche Einzelheiten erfahren wir im Anzeigentext herzlich wenig. Der Akkumulator ("Sie sparen teure Batterien") kann zum Problem werden. Wenn er sich nicht mehr aufläd, dann müssen Sie ein neues Gerät kaufen.
Dann ist da noch der sehr klein gedruckte Text, in dem zufriedene Anwender zu Wort kommen. Auch ein Arzt berichtet aus dem Seniorenstift: "Gut im Test". Was für ein Test denn? Diese Marketing-Texte sollte man nicht ernst nehmen.
Wer hierzulande ein Hörgerät benötigt, bekommt auch eins. Wo ist also der Markt für so ein Produkt in Deutschland? Man braucht sich auch nicht ohne Hörgerät durchzugeln. Ein großer Prozentsatz der Bevölkerung läuft sowieso mit Stöpseln im Ohr herum. Ein moderne Hörgerät fällt im Alltag kaum auf. Wo ist also der Markt für so ein Produkt in Deutschland? Ich könnte mir vorstellen, dass es sich um die Altersgruppe der 50-70jährigen handelt. Man fühlt sich noch nicht wirklich alt, aber es treten doch schon Einschränkungen auf, die man verdrängen will. Hörgerät klingt da vielleicht eher nach Alter. Warum da für Hörhilfe nicht der Fall sein soll, ist mir schleierhaft, denn z.B. im Englischen heißen die Hörgeräte hearing aids, also Hörhilfen. Und nach Wikipedia ist die Hörhilfe „eine allgemeine, unspezifische Bezeichnung für eine Vielzahl unterschiedlicher Hör-Hilfsmittel für schwerhörige Menschen.“ Link: http://de.wikipedia.org/wiki/H%C3%B6rhilfe  
Ich glaube, dass die Mikrochip-Hörhilfe für den Weltmarkt der nicht Krankenversicherten geschaffen wurde und preiswert in China oder Südkorea hergestellt wird, den Händler wahrscheinlich 6,72 € kostet, um dann für 98 € verkauft zu werden. Aber das ist zugegebenermaßen Spekulation.

Insgesamt halte ich die Mikrochip-Hörhilfe für Abzocke. Mein Rat: wenn Sie eine Hörminderung bei sich feststellen, lassen Sie durch einen HNO-Arzt die Art und den Grund herausfinden, und die Hörhilfe sollte dann das vom Fachmann (Hörgeräteakustiker) angepaßte Hörgerät sein.

Nachtrag: ich habe ein ähnliches Produkt gefunden, das bei Abnahme von 500 Stück 8,39 € kostet, es heißt: Light Small Sound Amplifier Adjustable Tone ITE Hearing Aid, Item T-HA-3002. Da lag ich doch gar nicht so schlecht.

 

Carpe Diem Haiku Hanabi (fireworks) (花火)

Rhine in flames fireworks

Seconds of flowering trees

All blossoms to pass

Beautiful fireworks

Colourful against the sky

All beauty must die

PS. The Rhine in Flames is an annual fireworks in Cologne. Düsseldorf has a Japanese Day, where one could also watch an exceptional fireworks show.
http://chevrefeuillescarpediem.blogspot.de/

Protein kinase inhibitors - hype or hope?

As we've seen quite a lot of compounts being studied during the past two years, I think it's to look how much hype or hope there is. Where do we stand after the EULAR 2013 Meeting?

This list is incomplete, I know, but it shows that our hopes are mixed with lots of hype. And this list is my personal interpretation; someone might disagree and should do so in the commentary part. Red stands for problems ot that I don't think it will develop into a drug on the market. Yellow stands for might develop into a drug, still to early. One could argue, if VX-509, ARRY-797, ASP015K, and Ruxolitinib still belong to this group. And only one in the green group.

I think that too many pharmaceutical companies tried to run for a small molecule, which is easier to produce, but might be sold at a high price.

I hope that we'll get these drug in the future, though well tested, safe, and not at the top pricing drug companies expect.

Xeljanz right now stands alone on the U.S. market. The European market will have to wait. Even if there is much hype, I hope for Xeljanz at least to make it to the European market.

Haibun Two Evenings

Today I went for a stroll in the evening. I have been near the stables, where you can smell the horses and hear them moving in the stables. The sky was still orange in the West. I listened to wind in the old oak trees, the constant rumble from the motorway, also some far noise from the marshalling yard, but more the twittering of birds. In the sky there were long dark clouds shifting in the wind in front of some light blue. I watched the swallows flying round and later, when it was getting darker the bats appeared. On the ground there were rabbits jumping through the high grass near the trodden football field, which looked funny. The colours were changing from green to grey. How peaceful this evening!

Wind in the oak trees

The orange sky in the West

Rabbits frolicking

Cool summer evening

Listening to birds and wind

Bats curving around

And I remembered an evening at Borobudur, Indonesia, three years ago, where I stayed at a small hotel looking across the paddy fields to a bamboo grove. The throbbing heat had stopped and I listened to the muezzin. There were also swallows, which disappeared with the falling night, and made place for the bats. The next morning I watched the bats moving under the roof tiles; then I knew why the cat was so busy on the ceiling above my room. In the early evening frogs were challenging the crickets.

Bamboo swaying

Behind the rice field

Birds calling the evening

Yellow bamboo leaves

Twirling down

As evening arrives

After the muezzin’s call

Bats circle above the paddy fields

The heat is leaving

Night has fallen

Shadow of the bamboo

Frogs challenging crickets

If I compare the two evenings, they are so different yet so much the same. Far away and home merging into a peaceful harmony.

Carpe Diem's Tan Renga Challenge #3 "the rainy season"

the rainy season

a paper lantern in hand

I walk along the verandah

(Buson)

closing doors and shutters

water gushing inside

the rainy season

a paper lantern in hand

I walk along the verandah

(Buson)

listening to rain on tiles

and a feeble cricket

http://chevrefeuillescarpediem.blogspot.se/  

Carpe Diem Haiku Yuunagi (夕凪)

Ripples on the lake

Summer breeze is arriving

With the evening

Spring evening

Clouds simply forget

The setting sun

Listening to the

Crystal wings of angels

In the afterglow

Warm humid evening

Reminiscing a tropical forest

Then the chorus of crickets

Evening starts

Hiding lights

But not fragrances

Evening moon

The silver of his light

Well hidden from thieves

http://chevrefeuillescarpediem.blogspot.de/ 

ASP015K at the EULAR 2013 Meeting

I thought very positively about ASP015K after the ACR 2013 meeting in Washington:
“ASP015K is an interesting small molecule as it may be efficacious against rheumatoid arthritis with less adverse events when compared to other small molecules. The data is preliminary and there’s still a long way to go. It would be nice, if Astellas Pharma could give the compound a name. Good luck from my side!”
http://rheumatologe.blogspot.de/2012/12/asp015k-at-acr-2012-in-washington.html

Could ASP015K keep up with its’ aspirations at the EULAR 2013 meeting?

S. Yamazaki and colleagues presented a study [THU0101]: “ASP015K: a novel JAK inhibitor demonstrated potent efficacy in adjuvant-induced arthritis model in rats”. As I had already seen this study in Washington, I don’t want to comment on it again; please look up the above link.

J. Garg and colleagues presented a new phase 1 and 2 study [THU0227]: “Pooled analysis of clinical safety data for ASP015K, a novel JAK inhibitor in development for treatment of autoimmune diseases”. Conclusions: “ASP015K administered as single or multiple doses for up to 42 days was safe and well tolerated in HVs/pts in 13 phase 1 and 2 studies.”

T. Zhu and colleagues presented the following study [THU0256]: “Pharmacodynamics of ASP015K, a novel janus kinase inhibitor, in healthy volunteers.” Conclusions: “ASP015K showed dose- and concentration-dependent inhibition of STAT5-P. Total lymphocyte count showed no dose-dependent changes. A dose-dependent reduction in NK cells was seen with multiple doses. These results are consistent with the pharmacologic effect of JAK1/3 inhibition by ASP015K.” I’m a bit surprised that this study is presented now – I would have expected it at the ACR 2012, half a year ago.

T. Zhu and colleagues presented [AB0363]: “Coadministration of ASP015K, a novel janus kinase inhibitor, with methotrexate demonstrates tolerability and lack of pharmacokinetic interactions in patients with rheumatoid arthritis”. Please look it up on the ACR 2012 blogpost, mentioned above.

My positive impression dwindles considerably! I hope we’ll see results from a phase 2b study later this year. And if ASP015K doesn’t have a name by then, it might never get a name.

Targeting interleukin-17 in patients with active rheumatoid arthritis?

MedLinx just has sent me an article on IL-17 by H. Kellner, which surprised me, as H. Kellner is one of the international known investigators of secukinumab.

H. Kellner presented an article: “Targeting interleukin-17 in patients with active rheumatoid arthritis: rationale and clinical potential”. In his article he discusses: “Clinical and experimental evidence suggest that interleukin-17A (IL-17A; also known as IL-17) is an attractive therapeutic target in rheumatoid arthritis (RA). Rheumatoid synovial tissue produces IL-17A, which causes cartilage and bone degradation in synovial and bone explants.” And: “Several IL-17A blockers, including the anti-IL-17A monoclonal antibodies secukinumab and ixekizumab, and the anti-IL-17 receptor subunit A monoclonal antibody brodalumab have been evaluated in phase II clinical trials.” Link: http://tab.sagepub.com/content/5/3/141.abstract?rss=1  

Ixekizumab: the recent EULAR 2013 Meeting in Madrid didn’t show lots of new data. I had the idea, that the two studies were published to keep a flickering light burning. For more see: http://rheumatologe.blogspot.de/2013/06/ixekizumab-at-eular-2013.html  

Secukinumab: At the last ACR Meeting (2012 in Washington) there have only been studies on secukinumab in ankylsosing spondylitis. Link: http://rheumatologe.blogspot.de/2012/12/secukinumab-at-acr-2012-in-washington.html. There had been a study on secukinimab in rheumatoid arthritis patients by M. Genovese, H. Kellner and colleagues at the 2012 EULAR Meeting, in which secukinumab didn’t meet the endpoint. See more: http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html.

Brodalumab: This drug showed a mild effect according to the presented study. See for more: http://rheumatologe.blogspot.de/2013/06/brodalumab-at-eular-2013.html. The study by P. Mease has been in patients with psoriatic arthritis.

All in all I doubt that we’ll hear much more about IL-17 in rheumatoid arthritis, but these drugs might be effective in psoriatic arthritis and/or spondyloarthropathies.

Carpe Diem Haiku Hototogisu

Hototogisu

Cry after cry unanswered

Like the brook’s murmur

Hototogisu

Too busy to watch the sky

Flies from nest to nest

Hototogisu

Calls through the forest

Soon to be milled

http://chevrefeuillescarpediem.blogspot.de/

GLPG0634 at the EULAR 2013

GLPG0634 is selective inhibitor of Janus kinase 1 (JAK-1). And I had been quite thrilled by this new drug at the ACR 2012 in Washington. Now, I was eager to see, what new developments would be presented at the EULAR 2013 in Madrid.

B. Vayssiere and colleagues presented a rodent study [THU0116]: “Biological effects of the jak1 selective inhibitor GLPG0634 on inflammation markers in arthritic mice”. Conclusions: “ … These data establish that selective JAK1 inhibition by GLPG0634 is sufficient to mediate strong efficacy in an established arthritis model …”. That wasn’t so thrilling.

F. P. Vanhoutte and colleagues presented [THU0229]: “Safety and efficacy of GLPG0634, a selective JAK1 inhibitor in patients with rheumatoid arthritis: results of a 4-week phase II a dose ranging, multi-center trial”. Conclusions: “These early clinical results demonstrate that selective inhibition of JAK1 by once-daily dosing of GLPG0634 from 75 mg to 300 mg is efficacious and generally well tolerated for 4-weeks treatment of RA, and confirm data from a previous study at a 200 mg daily dose. A dose of 30 mg QD was suboptimal for efficacy. Larger, longer term studies in RA are being initiated to evaluate optimal doses for efficacy and safety.” I looked into the results and agree with the authors’ conclusions.

F. Namour and colleagues presented a third study [THU0236]: “Once-daily dosing of GLPG0634, a selective JAK1 inhibitor, is supported by its active metabolite“. Conclusions: “The results of these studies indicate that an active metabolite supports the activity of GLPG0634. The long half-life of this metabolite provides a lasting effect, though at a lower level of JAK1 inhibition than GLPG0634. …”.

As EMEA seems to be reluctant to approve tofacitinib, maybe GLPG0634 has a better chance. With two PK inhibitors prices might come down to level, where it’s affordable for society. So I wish both drugs good luck!

Link:
http://rheumatologe.blogspot.de/2012/12/glpg0634-at-acr-2012-in-washington.html