Zu Abkürzungen von anti-rheumatischen Medikamenten

Ich las den den Artikel von T. Schmeiser et al.[1]. Und da waren sie wieder, die Abkürzungen, die ich so nicht mag. Ich halte es für eine gute Idee, Medikamente mit drei Buchstaben abzukürzen, aber es muss nicht jedes Land seine eigenen Abkürzungen produzieren. Flughäfen haben solche Abkürzungen mit drei Buchstaben. Der Flughafen Köln/Bonn wird CGN abgekürzt und kein Reiseveranstalter käme auf die Idee, plötzlich KLN oder KÖL zu benutzen.

Ich hatte bereits über diese Art von Abkürzungen vor etwa acht Jahren schon einmal berichtet [2].

Bei neun Medikamenten sind Abweichungen zum Gebrauch im Abstract-Band des 2019 ACR Meetings [3] vorhanden.

Bei Abatacept ist die von Schmeiser gewählte Alternative sogar besser, da weniger fehleranfällig gegenüber Adalimumab.

Baricitinib wird in den Studien des 2019 ACR Meeting mit bari abgekürzt. BAR ist prinzipiell in Ordnung, führt einen aber beim Suchen auf „bar“-Diagramme.

Certolizumab mit CMZ abzukürzen ist nur vom deutschen Medikamentennamen (Cimzia) her zu erschließen.

ETA für Etanercept finde ich nicht gut, weil es im Japanischen ein schlechten Beigeschmack hat [4].

Golimumab – warum nur GOM? GOL ist einsichtiger.

Für Infliximab war auch schon IFX in Gebrauch. IFN kann als Abkürzung von Infusion verwechselt werden.

Für SAR als Abkürzung für Sarilumab habe ich noch keinen Beleg. Wäre prinzipiell nichts gegen einzuwenden.

Für Tocilizumab hatte ich früher TOC gefunden, durchgesetzt hat sich TCZ. TOC wäre auch einleuchtender als TOZ.

Selbstverständlich kann jeder seine Abkürzungen so wählen, wie sie dann im Abkürzungsverzeichnis stehen. Verständlicher ist man aber, wenn man einen Konsens für Abkürzungen herstellt.

Links und Literatur:

[1] Schmeiser, T., Broll, M., Dormann, A. et al. Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie – eine Situationsanalyse. Z Rheumatol 79, 379–384 (2020). https://doi.org/10.1007/s00393-020-00800-8 ABC:

[2] https://rheumatologe.blogspot.com/2012/11/abkurzungen-fur-dmards-in-der-s1.html
[3] 2019-Abstract-Supplement.pdf https://acrabstracts.org/download-abstracts/
[4] https://rheumatologe.blogspot.com/2016/12/whats-in-names-of-drugs-in-rheumatology.html
Edward S. Herman, Noam Chomsky: Manufacturing Consent. Pantheon Books, New York 2002.

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Biosimilars und Biologika auf dem DGRh Kongress 2017 in Stuttgart

Warum ist die Politik so daran interessiert, warum Krankenkassen, Patientenverbände, Fachgesellschaften? Weil sie zuvor ihre Hausaufgaben nicht gemacht haben. Denn sie haben der Preisexplosion nicht Einhalt geboten. Das fing schon vor den Biologika an, aber hierbei ist es doch besonders offensichtlich – und ein Ende ist da nicht in Sicht, wenn wir an die small molecules wie Tofacitinib oder Baricitinib denken. So steigen die Preise weiter an. Der Markt wird immer unüberschaubarer.

Biosimilars kommen wie Innovationen daher, als hätte die Welt darauf gewartet, aber es sind schließlich nur  Imitate; die entscheidenden Ideen haben andere gehabt und in Studien die Wirksamkeit nachgewiesen. Die  Patienten jedenfalls werden damit überfordert. Insbesondere wo es neben Biosimilars auch schon Bioidenticals gibt. Auch wenn ich nicht auf Biosimilars gewartet habe, werde ich sie denooch anwenden, besser anwenden müssen.

Welche Biosimilars haben wir denn? Welche Biologika wurden denn vorgestellt? Gab es funkelnagelneue Bio***s? In dieser Übersicht werde ich mich auf den Einsatz dieser Medikamentengruppe in der Therapie der rheumatoiden Arthritis, der Psoriasisarthritis und den seronegatiben Spondyloarthritiden beschränken.

Biosimilar-Kandidaten zu Humira® (Adalimumab) BI 695501 von Boehringer Ingelheim - ENCORE.42 (Encore sind Poster, die bereits anderswo gezeigt wurden) - das Poster beschäftigt sich mit dem Autoinjektor. Encore.47 beschäftigt sich mit Wirksamkeit und Nebenwirkung und findet keinen wesentlichen Unterschied.

Ansonsten fanden sich viele Poster zu Secukinumab, aber auch Daten zu Tocilizumab, Certolizumab, Canakinumab, Sarilumab, Abatacept, Golimumab, Rituximab, Ixekizumab und Infliximab.

H. Kellner präsentierte Daten aus seiner Schwerpunktpraxis (EV.13): " Hohe Patientenakzeptanz bei Neueinstellung oder Umstellung von Originalabiologika (Enbrel, Remicade) auf Biosimilar-TNF Ak". Die Arbeit hat nur geringe Fallzahlen. In der Schlussfolgerung lesen wir: "Den angesprochenen Patienten ist die Möglichkeit einer substanziellen Kostenersparnis bei Einsatz von Biosimilar durchaus bewußt und ein wesentliches Element der Bereitschaft selbst Biosimilars zu verwenden." Das kann ich so aus den Ergebnissen nicht herauslesen. Ob eine Kostenersparnis dauerhaft gegenüber den Originalherstellern bestehen bleibt, muss die Zukunft zeigen, denn es wird wahrscheinlich zu Festpreisen kommen.

Zusammenfassend spielen die Biosimilars in der Wissenschaft eine untergeordnete Rolle. Das liegt in der Natur der gesetzlichen Bestimmungen, denn es muss nur der Nachweis von gleicher Effektivität und Nebenwirkung zum Orinalpräparat in einer Indikation nachgewiesen werden. Das sollte auch leicht möglich sein, wenn die Strukturgleichheit gegeben ist - und davon ist auszugehen. Für Infliximab haben wir die Biosimilars Remsima®, Inflectra® und Flixabi®, wovon Remsima® und Inflectra® bioidentisch sind, d.h. sie haben einen Hersteller und zwei Vertreiber. Für Etanercept haben wir die Biosimilars Benepali® und Erelzi™. Für Rituximab ist das Biosimilar Truxima® zugelassen. Für Adalimumab ist das Biosimilar Amjevita™ in den USA zugelassen und wird neben anderen hier in der nahen Zulunft erwartet [1].

Für die o.g. Originalpräparate ist eine Fülle von neuen Daten veröffentlicht worden. Allerdings habe ich nichts zu Mavrilimumab und Vobarilizumab gefunden.

Links:

[1] http://rheumatologe.blogspot.de/2016/12/possible-problems-with-piosimilars.html

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Monoklonale Antikörper nach dem Kongress der amerikanischen Gesellschaft für Rheumatologie (ACR) in San Francisco (2015)

Ich habe in den letzten Wochen bereits ausführlich in Englisch über die wissenschaftlichen Erkenntnisse beim Jahreskongress des American College of Rheumatology 2015 in San Francisco berichtet. Der ACR 2015 der europäische Kongress EULAR 2015 sind die großen Kongresse in der Welt der Rheumatologie gewesen. Auf diesen Kongressen werden die neuesten Studien vorgestellt und mindestens als Zusammenfassung zugänglich gemacht.

Im folgenden Text sind die Links Verweise auf diesen Blog, aber auf die Artikel in Englisch.

Monoklonale Antikörper

Monoklonale Antikörper sind Biologika, d.h. sie werden in Zellkulturen hergestellt. Sie tragen die Enddung  „…mab“ im Substanznamen (also nicht im Namen des Präparates) und das steht für „monoclonal antibody“. Am Substanznamen kann man erkennen, welcher Herkunft das Protein ist, gegen das sich der Antikörper richtet: Antikörper von der Maus tragen die Endung –omab, von Primaten die Endung –imab, chimäre Antikörper (ein Teil des Antikörpers ist Mausprotein) die Endung –ximab, humanisierte Antikörper die Endung, humane Antikörper die Endung –umab. Beispiele aus der Rheumatologie sind: Adalimumab, Belimumab, Certolizumab, Golimumab, Infliximab, Rituximab, Tocilizumab, Secukinumab, Ustekinumab.  In der Entwicklung sind: Brodaluma, Mavrilimumab, Sirukumab und weitere mehr.

Mavrilimumab

Auf dem ACR 2015 wurden zwei Studien zu Mavrilimumab vorgestellt. Was fehlt noch für eine Zulassung? Es gibt noch keine Phase-3-Studie und noch keine Daten zur Hemmung der radiologischen Progression. Meine Vermutung ist, dass wir warten müssen, bis 104 Wochen Daten veröffentlicht werden. Aber ich war bereits skeptisch und im Laufe der Zeit bin ich noch skeptischer geworden. Wir haben auch nichts mehr von MOR103, einem anderen humanen, monoklonalen Antikörper gegen Granulozyten-Makrophagen-Kolonie-stimulierender Faktor-Rezeptor-α (GM-CSFR-α) gehört. Ich hoffe allerdings immer noch, dass dieses Konzept aufgeht, da wir einen Mangel an Biologika mit alternativen Wirkweisen haben, aber überzeugt bin ich immer noch nicht. Ich hoffe, dass dies im nächsten Jahr ändern wird. Link zum Artikel auf Englisch: http://rheumatologe.blogspot.de/2015/11/mavrilimumab-at-acr-2015-meeting-in-san.html

Secukinumab

Es wurden mehr als 10 Publikationen über Secukinumab auf der Jahrestagung ACR 2015 in San Francisco vorgestellt. Secukinumab richtet sich gegen den Interleukin-17A-Rezeptor. Secukinumab stand bereits unter dem Namen Cosentyx in Deutschland für die Indikation von mittelschwerer bis schwerer Plaque-Psoriasis zur Verfügung. Nach dem Kongress und zwar seit dem 26.11.2015 ist Cosentyx in Deutschland auch in den Indikationen Psoriasis-Arthritis und Morbus Bechterew zugelassen. Link: http://rheumatologe.blogspot.de/2015/11/secukinumab-at-acr-2015-meeting-in-san.html.

Sarilumab

Es gab einige Veröffentlichungen zu Sarilumab auf dem ACR 2015 in San Francisco. Sarilumab ist ein monoklonaler Antikörper gegen IL-6, einem Botenstoff (Zytokin). Ich denke, dass die Anzahl der Studien darauf hindeutet, dass Sanofi Sarilumab auf den Markt bringen will; aber es ist noch zu früh, um für eine Zulassung der FDA zu beantragen. Ich verfolge die Entwicklung rund um Sarilumab seit ein paar Jahren. Ich hoffe immer noch, dass das Medikament auf den Markt kommt. Aber ... brauchen wir Sarilumab? Was könnte Sarilumab uns geben, das wir nicht von Tocilizumab bekommen? Werde ich meine IL-6-Inhibitor-Patienten in zwei Gruppen aufteilen? Im Moment kann ich diese Fragen nicht beantworten. Und wir benötigen immer noch Daten über die radiologische Progression. Link: http://rheumatologe.blogspot.de/2015/11/sarilumab-at-acr-2015-meeting-in-san.html.

Tregalizumab

Es hat war eine Veröffentlichung zu Tregalizumab auf dem ACR 2015 in San Francisco gegeben. Tregalizumab (BT-061) ist ein humanisierter, anti-CD4-mAb und induziert selektiv Treg-Aktivierung in vitro.  Es scheint ein interessantes Konzept zu sein; die Autoren der Studie weisen darauf hin: "In früheren Studien wurde vorgeschlagen, die Wirksamkeit bei RA in Dosen ≥25 mg subkutan (SC).“ Aber lassen Sie uns zu den düsteren Wahrheiten der Studie kommen. Die Autoren schlussfolgerten aus ihren Daten: "Keine der getesteten Dosen von Tregalizumab zeigte eine signifikante Wirksamkeit in Hinsicht auf die Verbesserung von Zeichen und Symptomen einer aktiven rheumatoiden Arthritis in Woche 12 und 24 (basierend auf ACR20) ...“. Bedeutet das nun, dass Tregalizumab aufgegeben werden sollte? Ich meine nicht. Wahrscheinlich wird das Team um Ronald van Vollenhoven eine neue Idee vorstellen, wie das Konzept doch funktionieren kann; vielleicht in Form einer Kombination.

Link: http://rheumatologe.blogspot.de/2015/11/tregalizumab-at-acr-2015-meeting-in-san.html.

Sirukumab

Es hat eine Veröffentlichung zu Sirukumab auf dem ACR 2015 in San Francisco gegeben. Sirukumab ist ein humaner MAB, der IL-6 bindet und für die Behandlung der rheumatoiden Arthritis entwickelt wurde. Also würde Sirukumab sich mit Tocilizumab und Sarilumab sich messen müssen. Dem Sponsor scheint aufgefallen zu sein, dass er der dritte Hersteller sein würde, der einen Anteil vom Tortenstück IL-6 bekommen will. Ich sehe einen Mangel an Engagement. Und tatsächlich sehe ich auch keinen medizinischen Grund, einen weiteren IL-6-Hemmer zu bekommen. Link: http://rheumatologe.blogspot.de/2015/11/sirukumab-at-acr-2015-meeting-in-san.html.

Brodalumab

Es hat eine Veröffentlichung zu Brodalumab auf dem ACR 2015 gegeben. Brodalumab ist ein anti-IL-17-Rezeptor MAB, ein viel versprechendes neues Prinzip am Horizont gegen Psoriasisarthritis wird der MAB schön geredet. Aber dann nur eine Studie! Die Auswertung der klinischen Daten der Phase-2-Studie ist nicht sehr überzeugend. Wo ist Daten über die radiologische Progression nach zwei Jahren? Der Sponsor scheint nicht die Agenda voranzutreiben. Ich sehe keinen Grund, warum nicht für eine Phase-3-Studie Patienten rekrutiert werden. Es sei denn, man wartet darauf, wie erfolgreich Secukinumab ist. Link: http://rheumatologe.blogspot.de/2015/11/brodalumab-at-acr-2015-meeting-in-san.html.

Certolizumab

Es gab 14 Publikationen zu Certolizumab auf der Jahrestagung ACR 2015 in San Francisco. Ich zitiere im englischen Text zwei Studien. Am 20. November bekam UCB eine positive Stellungnahme vom CHMP (Ausschuss für Humanarzneimittel) der EMA (European Medicines Agency) für Certolizumab Pegol (Cimzia) bei schwerer, aktiver und progressiver rheumatoider Arthritis DMARD-naive Patienten zu behandeln. D.h. man kann das Präparat sehr viel früher einsetzen. Link: http://rheumatologe.blogspot.de/2015/12/certolizumab-part-1-at-acr-2015-meeting.html.

Tanezumab

Es hat eine Veröffentlichung zu Tanezumab bei Arthrose(!!!) auf der Jahrestagung ACR 2015 in San Francisco gegeben. Nach 2013 haben wir nicht viel über Tanezumab gehört, weil die FDA einen teilweisen klinischen Stopp der Studien außerhalb von Krebserkrankungen aufgrund von unerwarteten Nebenwirkungen dem Hersteller auferlegt hatte. Pfizer kündigte Anfang dieses Jahres an, die Phase 3 Studien zu chronischen Schmerzen für Tanezumab wieder aufzunehmen. Tanezumab ist ein humanisierter monoklonaler Antikörper, der selektiv auf den Nervenwachstumsfaktor (NGF), einem Regulator der Schmerzverarbeitung und Empfindlichkeit, gerichtet ist. Ich habe meine Probleme mit dem Wiedererscheinen von Tanezumab in der Behandlung von Arthrose-Schmerzen. Die Studien dauerten nicht lange genug an, um die langfristige Sicherheit zu bewerten. Die Auswertung der alten Daten sagt uns nicht, ob Tanezumab besser als Naproxen, Celecoxib oder Oxycodon ist. Sie sagt uns, dass Tanezumab besser als Placebo ist. Hurra! Aber mal sehen, ob das Phase-3-Programm belastbare Daten bringt. Link: http://rheumatologe.blogspot.de/2015/12/tanezumab-in-osteoarthritis-at-acr-2015.html.

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Secukinumab at the ACR 2015 Meeting in San Francisco

There have been more than 10 publications on secukinumab at the ACR 2015 Annual Meeting in San Francisco. I feel like watching a poker game in the end phase, an all-in-call.

Xenofon Baraliakos and colleagues looked at: “Effect of Interleukin-17A Inhibition on Spinal Radiographic Changes through 2 Years in Patients with Active Ankylosing Spondylitis: Results of a Phase 3 Study with Secukinumab”. Conclusion: “[…]No radiographic progression was observed in ~80% of the pts receiving secukinumab over 104 wks. […]”. Since the tofacitinib debacle concerning EMEA approval, we know how important radiographic data are.

Juergen Braun and colleagues presented: “Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing”. In conclusions the authors state: “Secukinumab 150 mg s.c. provided sustained improvements over 52 weeks in the signs and symptoms of AS, reducing inflammation, and improving physical function and health-related quality of life. Secukinumab was well tolerated; safety findings were consistent with previous reports.”

The second set of studies is on psoriatic arthritis.

Arthur Kavanaugh and collegues looked at: “Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis in Anti-TNF-Naive Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Dosing”. Conclusion: “Secukinumab provided sustained improvements in the signs and symptoms of PsA in both anti‒TNF-naïve and anti‒TNF-IR pts.”.

I’ll skip a few interesting studies, but will list these under references.

Alice B. Gottlieb and colleagues presented: “Secukinumab Reduces the Burden of Nail and Skin Disease in Patients with Psoriasis and Patients with Psoriatic Arthritis: Results from Two Phase 3 Studies”. Conclusion: “Secukinumab improved nail and skin symptoms in pts with psoriasis with significant nail involvement and in pts with concomitant PsA and nail involvement.” I guess, we all expected that it would be this way!

And Alice B. Gottlieb also presented: “Secukinumab Improves Skin Symptoms and Physical Functioning Compared with Ustekinumab in Patients with Moderate to Severe Psoriasis with Concomitant Psoriatic Arthritis: Subanalysis of a Randomized, Double Blind, Parallel-Group, Active Comparator-Controlled Phase 3b Trial”. Conclusion: “Secukinumab was superior to ustekinumab at improving skin symptoms in patients with moderate to severe plaque psoriasis. In the small sub-group of patients with psoriasis and concomitant PsA, secukinumab showed a trend for improving skin symptoms and physical functioning compared with ustekinumab.” I must admit that this surprised me.

Laure Gossec an colleagues looked at: “Relationship Between Improvements in Fatigue and Signs & Symptoms of Active Psoriatic Arthritis: a Sub-Analysis of a Phase 3 Study with Secukinumab”. Conclusion: “Secukinumab improved fatigue in patients with active PsA regardless of prior anti-TNF therapy. A relationship between improvement in fatigue and improvements in the signs and symptoms of PsA was only shown for ACR 20 response and not for other assessments of disease. These results suggest that fatigue in PsA is not strongly related to disease activity but was still improved by secukinumab.” I’ll have to look all over the studies if improvement of fatigue has been addressed elsewhere.

Secukinumab is already available under the name Cosentyx in Germany for the indication of moderate to severe plaque psoriasis. In the U.S. Secukinumab had been approved by the FDA even earlier. Now, we rheumatologists have to wait, until FDA and/or EMEA approve the use in psoriatic arthritis, ankylosing spondylitis, and other inflammatory rheumatic conditions. I’ll be happy to have a new tool, though we still don’t know if a certain consecutive order of biologics and the small molecule should be recommended.

PS. Since yesterday (26.11.2015) Cosentyx has been approved in Germany for the indications of psoriatic arthritis and ankylosing spondylitis. So, the waiting is over.

References.

Baraliakos X, Deodhar AA, Braun J, Baeten D, Dougados M, Sieper J, Emery P, Readie A, Martin R, Mpofu S, Richards H. Effect of Interleukin-17A Inhibition on Spinal Radiographic Changes through 2 Years in Patients with Active Ankylosing Spondylitis: Results of a Phase 3 Study with Secukinumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/effect-of-interleukin-17a-inhibition-on-spinal-radiographic-changes-through-2-years-in-patients-with-active-ankylosing-spondylitis-results-of-a-phase-3-study-with-secukinumab/. Accessed November 16, 2015.

Braun J, Deodhar AA, Sieper J, Dougados M, Porter B, Andersson M, Richards H. Secukinumab Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-significantly-improves-signs-and-symptoms-of-active-ankylosing-spondylitis-52-week-results-from-a-randomized-double-blind-placebo-controlled-phase-3-trial-with-subcutaneous-loading-and/. Accessed November 16, 2015.

Kavanaugh A, McInnes IB, Mease PJ, Hall S, Chinoy H, Kivitz AJ, Patekar M, Wang Z, Mpofu S. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Psoriatic Arthritis in Anti-TNF-Naive Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial with Subcutaneous Dosing [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-psoriatic-arthritis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from-a/. Accessed November 16, 2015.

Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewé RBM, Nash P, Pricop L, Wang Z, Mpofu S. Secukinumab Provides Sustained Improvements in Psoriatic Arthritis: 2-Year Efficacy and Safety Results from a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-psoriatic-arthritis-2-year-efficacy-and-safety-results-from-a-phase-3-randomized-double-blind-placebo-controlled-trial/. Accessed November 16, 2015.

Gottlieb AB, Reich K, Wang Z, Milutinovic M, Mpofu S. Secukinumab Reduces the Burden of Nail and Skin Disease in Patients with Psoriasis and Patients with Psoriatic Arthritis: Results from Two Phase 3 Studies [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-reduces-the-burden-of-nail-and-skin-disease-in-patients-with-psoriasis-and-patients-with-psoriatic-arthritis-results-from-two-phase-3-studies/. Accessed November 16, 2015.

Gottlieb AB, Thaci D, Blauvelt A, Milutinovic M, Mpofu S. Secukinumab Improves Skin Symptoms and Physical Functioning Compared with Ustekinumab in Patients with Moderate to Severe Psoriasis with Concomitant Psoriatic Arthritis: Subanalysis of a Randomized, Double Blind, Parallel-Group, Active Comparator-Controlled Phase 3b Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-improves-skin-symptoms-and-physical-functioning-compared-with-ustekinumab-in-patients-with-moderate-to-severe-psoriasis-with-concomitant-psoriatic-arthritis-subanalysis-of-a-randomized-d/. Accessed November 16, 2015.

Betts KA, Mittal M, Joshi A, Song J, Bao Y. Relative Efficacy of Adalimumab Versus Secukinumab in Active Psoriatic Arthritis: A Matching-Adjusted Indirect Comparison [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/relative-efficacy-of-adalimumab-versus-secukinumab-in-active-psoriatic-arthritis-a-matching-adjusted-indirect-comparison/. Accessed November 16, 2015.

Gossec L, Kvien TK, Conaghan PG, Østergaard M, Cañete JD, Gaillez C, Mpofu S, Sherif B, Jugl S. Relationship Between Improvements in Fatigue and Signs & Symptoms of Active Psoriatic: Arthritis a Sub-Analysis of a Phase 3 Study with Secukinumab [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/relationship-between-improvements-in-fatigue-and-signs-symptoms-of-active-psoriatic-arthritis-a-sub-analysis-of-a-phase-3-study-with-secukinumab/. Accessed November 16, 2015.

Mease PJ, McInnes IB, Gottlieb AB, Widmer A, Pricop L, Mpofu S. Secukinumab Safety and Tolerability in Patients with Active Psoriatic Arthritis and Psoriasis: Results from a Pooled Safety Analysis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-safety-and-tolerability-in-patients-with-active-psoriatic-arthritis-and-psoriasis-results-from-a-pooled-safety-analysis/. Accessed November 16, 2015.

Deodhar AA, Baeten D, Sieper J, Porter B, Widmer A, Richards H. Safety and Tolerability of Secukinumab in Patients with Active Ankylosing Spondylitis: Pooled Safety Analysis of Two Phase 3, Randomized, Controlled Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/safety-and-tolerability-of-secukinumab-in-patients-with-active-ankylosing-spondylitis-pooled-safety-analysis-of-two-phase-3-randomized-controlled-trials/. Accessed November 16, 2015.

Baeten D, Blanco R, Geusens P, Sieper J, Jui-Cheng T, Martin R, Porter B, Richards H. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis in Anti-TNF-Naïve Patients and Those Previously Exposed to Anti-TNF Therapy: 52-Week Results from Two Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-in-anti-tnf-naive-patients-and-those-previously-exposed-to-anti-tnf-therapy-52-week-results-from/. Accessed November 16, 2015.

Baeten D, Braun J, Sieper J, Dougados M, Deodhar AA, Baraliakos X, Porter B, Gong Y, Richards H. Secukinumab Provides Sustained Improvements in the Signs and Symptoms of Active Ankylosing Spondylitis: 2-Year Efficacy and Safety Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/secukinumab-provides-sustained-improvements-in-the-signs-and-symptoms-of-active-ankylosing-spondylitis-2-year-efficacy-and-safety-results-from-a-phase-3-randomized-double-blind-placebo-controlled/. Accessed November 16, 2015.

Cowardice or icecold reckoning? A Glimpse into medical studies

Today I have read an article by R.G. Langley and colleagues on Secukinumab in Plaque Psoriasis (Link: http://www.ncbi.nlm.nih.gov/pubmed/25007392). I’m interested in Secukinumab (last blogpost is here: http://rheumatologe.blogspot.de/2014/07/secukinumab-at-eular-2014-meeting-in.html), but something came to my mind while reading. In this study secukinumab has been tested versus etanercept. Why? Why not adalimumab? Maybe because the sponsor thinks that adalimumab works better in psoriatic arthritis than etanercept? Cowardice or icecold reckoning?

M. Schiff and colleagues reported on the AMPLE trial (Link: http://www.ncbi.nlm.nih.gov/pubmed/23962455). The AMPLE trial is a head-to-head comparison of subcutaneous etanercept versus adalimumab for rheumatoid arthritis. Why not etanercept? Maybe because the sponsor thinks that etanercept works better in rheumatoid arthritis than adalimumab? Cowardice or icecold reckoning?

F. Buttgereit and colleagues published a study on modified release prednisone (Link: http://www.ncbi.nlm.nih.gov/pubmed/18207016) in rheumatoid arthritis. Under methods we read: “The modified-release tablet was taken at bedtime and prednisone was released with a delay of 4 h after ingestion. This treatment was compared with morning administration of immediate-release prednisone as an active comparator.” I don’t want to dwell on the fact, that “prednisone was released with a delay of 4 h after ingestion” has nothing to do with the method, but rather on the fact that the comparator was administered in the morning and not in the evening. Why not? Maybe because the sponsor thinks that an unequal comparison works better? Cowardice or icecold reckoning?

To sum it up, I think that we have to look at studies very carefully. In the above studies I don’t question the results but the design, which might influence the results. Cowardice or icecold reckoning? I think the latter one!

Secukinumab at the EULAR 2014 Meeting in Paris

Secukinumab is an anti-IL-17a MAB. I'm pretty sure, it won't work in rheumatoid arthritis patients, but we need more drugs in the field of treating patients with psoriatic arthritis. 

A. Gottlieb and colleagues presented the following study [AB0738]: "SECUKINUMAB REDUCES HSCRP LEVELS IN SUBJECTS WITH MODERATE-TO-SEVERE PLAQUE PSORIASIS AND CONCOMITANT PSORIATIC ARTHRITIS: A SUB-ANALYSIS FROM THE PHASE 3 ERASURE STUDY". Conclusions: "In subjects with psoriasis and concomitant PsA, secukinumab was associated with pronounced and sustained reductions in serum hsCRP levels indicating a reduction in inflammatory burden during secukinumab therapy."

I won't call it a major breakthrough, but it's enough to keep me interested. Hope to hear more about secukinumab in the future.

Link:

http://rheumatologe.blogspot.de/2013/06/secukinumab-at-eular-2013-meeting.html

Ankylosing spondylitis and Secukinumab

There’s a new (?) study on secukinumab in ankylosing spondylitis in The Lancet. I’ve seen similar, but not identical publications on secukinumab during the past year. I think we get to know different details on one ongoing study. I think that secukinumab isn’t working in rheumatoid arthritis, but it might work in psoriatic arthritis and ankylosing spondylitis (AS). So I think it’s a good idea to get ongoing information.

D. Baeten and colleagues published: “Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial”. The study looked at i.v.  secukinumab (2×10 mg/kg) compared to placebo. Results showed: “At week 6, ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99·8% probability that secukinumab is superior to placebo). One serious adverse event (subcutaneous abscess caused by Staphylococcus aureus) occurred in the secukinumab-treated group.” Conclusion: “Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated.” The drug needs to perform better than ASAS20 in larger studies!

X. Baraliakos and colleagues presented a poster at the 2012 ACR Meeting [574]: “Long Term Inhibition of Interleukin (IL)-17A with Secukinumab Improves Clinical Symptoms and Reduces Spinal Inflammation As Assessed by Magnetic Resonance Imaging in Patients with Ankylosing Spondylitis.” Conclusion: “This exploratory MRI analysis shows that the IL-17 inhibitor secukinumab may reduce spinal inflammation and this effect may be sustained for up to 24 months using a lower dose in the maintenance compared to induction phase.”

Do these results warrant a phase 2 study? By all means – yes! Please go ahead! We have patients suffering from ankylosing spondylitis, who are in desperate need for another mode of action, as TNF-alpha inhibition isn’t working. So, an IL-17A inhibitor would be most welcome. 

Rheumatoid Arthritis and future treatments by MABs

I’ve read an abstract recently on “Monoclonal antibody treatments for rheumatoid arthritis” by L. Bossaller and A. Rothe (Link: http://www.ncbi.nlm.nih.gov/pubmed/23789825).
As we already have quite a number of agents and more will be added, let’s have a look at targets already being uses successfully and possible targets.

TNF-alpha: TNF stands for tumor necrosis factor. We already have five TNF-alpha-Inhibitors.

IL-6: IL stands for interleukin. Interleukins for a large group of cytokines, which have the task to communicate between white blood cells (leukocytes), hence the word interleukins. IL-6 is a multitask cytokine, which induces acute phase proteins, plays a role in B cell differentiation and hepatocytes as well as others. We already use one IL-6 inhibitor – tocilizumab. Another IL-6 inhibitor is near to be launched: Sarilimumab (Link: http://rheumatologe.blogspot.de/2013/07/sarilumab-at-eular-2013-meeting.html). An we have an anti-IL-6 receptor nanobody® (ALX-0061), which would be different to the the MABs, but also interfering with the IL-6 signal.

IL-1: we already have anakinra, an interleukin-1 receptor antagonist, which isn’t as successful as TNF alpha inhibitors, when it comes to rheumatoid arthritis. Anakinsa is successful in some familial periodic fever syndromes. Maybe to treat RA it’s the wrong approach.

IL-17: some IL-17 inhibitors are studied in rheumatoid arthritis: secukinumab, ixekizumab and brodalumab (Link: http://rheumatologe.blogspot.de/2013/06/targeting-interleukin-17-in-patients.html). I’m not too optimistic we’ll hear much more about IL-17 inhibition as a treatment of rheumatoid arthritis.

VEGF: Vascular endothelial growth factor is a signal protein that stimulates vasculo-/angiogenesis. TNF alpha stimulates the release of VEGF in rheumatoid arthritis, so that more capillaries are formed and permeability of vessels is increased, which would result in more swelling. “VEGF – appears to be a promising avenue for the future treatment of RA.” Were the concluding remarks of Ewa M Paleolog in 2002 (Link: http://www.biomedcentral.com/content/pdf/ar575.pdf). As we haven’t heard more by now, it doesn’t seem to be the broad road to a successful therapy.

RANKL: it’s the receptor activator of nuclear factor kappa-B ligand, which is important for otheoclast formation and differentiation. Osteoclasts break down bone tissue. As this is what happens in erosions, RANKL is interesting in the treatment of rheumatoid arthritis. We already have denosumab, a RANKL inhibitor (MAB), which has been developed against osteoporosis, and is effective against erosions, but it isn’t effective against articular signs and symptoms of rheumatoid arthritis (Link: http://www.hopkinsarthritis.org/arthritis-news/denosumab-suppresses-erosions-but-has-no-effect-on-articular-signs-and-symptoms-in-rheumatoid-arthritis/).


B-cell function (CD20 [rituximab], CD38 [only of use in leukaemia?], B-cell activating factor [doubtful in RA], transmembrane activator and calcium-modulating and cyclophilin interactor) T-cell function (CD3 [CIA study in 2010], CD4 [no big breakthrough during the past 3 years], CD28 [?]) will be added later.

CD 20: We have rituximab. Other MABs are being studied: ocaratuzumab, which failed to show new data at the EULAR 2013 (Link to more information: http://rheumatologe.blogspot.de/2012/12/ocaratuzumab-at-acr-2012-in-washington.html), or ocrelizumab, which also failed to show new data at the EULAR 2013 (Link: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html). But there’s also ofatumumab, on which there had been news prior to the EULAR meeting (Link: http://rheumatologe.blogspot.de/2013/06/ofatumumab-just-before-eular-2013.html). All in all there is activity to get a new anti-CD 20 MAB, but it isn’t a new principle. So it’s only someone else reaching for the pie.

CD 38: There’s bortezomib being tested in multiple myeloma. A. Chillemi and colleagues don’t mention rheumatoid arthritis in a recent overview article (Link: http://molmed.org/files/1047).

BAFF: Tabalumab is an anti-BAFF Monoclonal Antibody, which has been disappointing at the EULAR 2013 (Link: http://rheumatologe.blogspot.de/2013/06/tabalumab-at-eular-2013-meeting.html), but there are two articles on tabalumab in the fresh from the press issue of the Annals of the Rheumatic Diseases (September 2013), so that I might have to revise my former statement on tabalumab. I’ll deal with this new information in a blog post of its’ own.

TACI: TACI is short for transmembrane activator and calcium modulator and cyclophilin ligand interactor, which also interacts with BAFF. There’s atacicept, but it isn’t working in RA (Link: http://rheumatologe.blogspot.de/2012/06/atacicept.html).

CD 3: There has been a CIA study in 2010, but I haven’t found anything new since then.

CD 4: The lack 0f CD 4 cell depletion in rituximab patients is associated with no response (Link: http://www.ncbi.nlm.nih.gov/pubmed/23918413). There had been a study in mice, which Rawarrior commented on 3 years ago (Link: http://rawarrior.com/will-cd4-lead-to-a-rheumatoid-arthritis-cure/). Since then nothing new.

CD 28: Do you remember TGN1412? Here’s the Wikipedia link: http://en.wikipedia.org/wiki/TGN1412. Maybe we do better not trying the luck of people again.   

To treat rheumatoid arthritis, we might get another IL-6 inhibitor (sarilimumab), another anti-CD 20 agent, and maybe tabalumab will prove to be effective (I’m still sceptical, but I’ll tell you more about the recent studies on tabalumab in another blog post).

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.

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.

Secukinumab at the ACR 2012 in Washington

Secukinumab is an Anti-Il17a Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html  

X. Baraliakos and colleagues tested secukinumab (IL-17A inhibition) in a proof-of-concept (PoC) trial and showed via MRI, that secukinumab may reduce spinal inflammation (Abstract No. 574). Conclusion: “This exploratory MRI analysis shows that the IL-17 inhibitor secukinumab may reduce spinal inflammation and this effect may be sustained for up to 24 months using a lower dose in the maintenance compared to induction phase. …”.

D. L. Baeten and colleagues presented another study on secukinumab in ankylosing spondylitis (Abstract No. 2225): “Improvement in Signs and Symptoms of Active Ankylosing Spondylitis Following Treatment with Anti-Interleukin (IL)-17A Monoclonal Antibody Secukinumab Are Paralleled by Reductions in Acute Phase Markers and Inflammatory Markers S100A8 and A9 (Calgranulin A and B)”. It’s a dose finding study with only 30 patients in a multicenter setting. Conclusion: “In this trial of secukinumab in AS, exploratory analyses of selected inflammatory markers suggest that secukinumab reduces CRP, S100A8 and S100A9, but only S100A8/9 reductions appear to correlate with clinical responses at Wk 6. …”.

There are some promising results, but secukinumab still has a long way to go.

Enhanced fatigue improvement from RA treatment with secukinumab

H. Kellner and colleagues presented a study on fatigue improvement at the 40th Congress of the German Society for Rheumatology (Deutsche Gesellschaft für Rheumatologie) at Bochum 19.-22.09.2012. Fatigue was assessed by using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the SF-36v2 vitality (VT) scale. As for the conclusion, please look below. It is interesting and promising that fatigue is addressed more and more by recent studies. A couple of years ago nothing much happened in the evaluation of this key complaint of our patients!

Enhanced fatigue improvement from RA treatment with secukinumab: An
application of IRT methodology
Kellner, Herbert, Prof. Dr.med. 1, Gnanasakthy, Ari 2, Kosinski, Mark 3, Durez, Patrick, Dr. med. 4, Mallya, Usha 2, Mpofu, Shephard, Dr. med. 5
Conclusions: IRT methods offer a promising approach to improving the measurement of fatigue in treatment studies of RA.

Ankylosing Spondylitis Refractory to TNF-inhibition in the light of EULAR 2012

There has been a recent publication of U. Kiltz et al.: “Treatment of Ankylosing Spondylitis in Patients Refractory to TNF-inhibition”, which is on the net at: http://www.medscape.com/viewarticle/761743
The authors have seen some trends for efficacy of abatacept, anakinra, apremilast, bisphosphonates, rituximab, secukinumab, sulfasalazine, thalidomide, and tocilizumab, but for problems with design and methodology of the evaluated studies “there is at present insufficient evidence to support a recommendation for any of these compounds.” So it came to my mind to look at what has been presented at the EULAR 2012 concerning these drugs and ankylosing spondylitis.

Abatacept – about 40 studies and posters, none on abatacept and ankylosing spondylitis.

Anakinra – around 40 studies, on in one abstract, anakinra is mentioned: “..the efficacy of anakinra, … has not been convincingly shown in AS”. ([SP0060] SPONDYLO-ARTHRITIS/ANKYLOSING SPONDYLITIS DRUG THERAPY / J. Braun. Rheumazentrum Ruhrgebiet, Herne, Germany)

Apremilast – no study in ankylosing spondylitis

Bisphosphonates – there’s a study by H. Forsblad-d'Elia on alendronate in osteoporotic patients with ankylosing spondylitis (NIS). They saw an increase in bone mineral density. In another study M. Soroush an colleagues looked at bone mineral density in ankylosing spondylitis patients with and without alendronate (NIS). They also saw an increase in bone mineral density in patients treated with alendronate. But actually these two studies were concerned rather with osteoporosis in patients with ankylosing spondylitis than treating ankylosing spondylitis with a bisphosphonate.


[THU0271] INCREASE IN BONE MINERAL DENSITY AND DECREASE IN WNT3A, OPG, CTX-I AND OSTEOCALCIN IN PATIENTS WITH ANKYLOSING SPONDYLITIS TREATED WITH ALENDRONATE
H. Forsblad-d'Elia, M. Nurkkala, K. Zetterberg, E. Klingberg, H. Carlsten, and Center for Bone and Arthritis Research. Department of Rheumatology and Inflammation Research, Institute of Medicine, Gothenburg, Sweden
Conclusions: We show, for the first time, a prompt and sustained decrease of the biomarkers Wnt3a, OPG, CTX-I and osteocalcin in osteoporotic AS patients treated with alendronate during 2 years. The results indicate a down regulatory effect on both osteclastic and osteblastic activity. The treatment also resulted in a significant and large increase in BMD in lumbar spine and total hip.

[AB0855] BONE MINERAL DENSITY IN PATIENTS WITH ANKYLOSING SPONDYLITIS BEFORE AND AFTER ONE YEAR TREATMENT WITH OR WITHOUT BISPHOSPHONATE
M. Soroush1, S. Soroush1, M. Mirtalebi2, B. Nadimi3. 1Rheumatology, Army University of Medical Sciences; 2Rheumatology; 3501 Hospital, Tehran, Islamic Republic Of Iran
Conclusions: Altogether, densitometry survey done over these two groups showed that T-score of diseased in both groups has been improved after treatment in comparison with the period they passed before treating, of course this amount of enhancement was more notable it the first group which received Alendronate.


Rituximab – about 40 studies, but only on abstract addressing the subject. D. Wendling and colleagues looked at data from the AIR registry. They saw moderate efficacy on several subsets of spondyloarthritis. I like to cite this abstract as Francis Berenbaum (@Larhumato) participated.


[AB0848] RITUXIMAB TREATMENT FOR SPONDYLOARTHRITIS. A NATIONWIDE SERIES: DATA FROM THE AIR REGISTRY
D. Wendling1, M. Dougados2, F. Berenbaum3, O. Brocq4, T. Schaeverbeke5, B. Mazieres6, C. Marcelli7, J.-M. Le Parc8, P. Bertin9, M. Robin10, J. Sibilia11, P. Lafforgue12, C. Prati1, B. Combe13, J.-E. Gottenberg11. 1Rheumatology, CHU, Besancon; 2Rheumatology, Cochin Hospital; 3Rheumatology, Saint-Antoine Hospital, Paris; 4Rheumatology, Princess Grace Hospital, Monaco; 5Rheumatology, CHU, Bordeaux; 6Rheumatology, CHU, Toulouse; 7Rheumatology, CHU, Caen; 8Rheumatology, Ambroise Paré Hospital, Boulogne-Billancourt; 9Rheumatology, CHU, Limoges; 10Internal Medicine, Hospital, Laon; 11Rheumatology, CHU, Strasbourg; 12Rheumatology, CHU, Marseille; 13Rheumatology, CHU, Montpellier, France
Conclusions: In this nationwide open experience of rituximab on several subsets of spondyloarthritis, we saw only a moderate efficacy, more evident for patients naive for anti TNF agents.

Secukinumab – 8 abstracts on secukinumab, but not an issue concerning ankylosing spondylitis save for the oberview by J. Braun, which I have already cited above.

Sulfasalazine – J. Sieper stated in his talk: “Furthermore, conventional DMARDs such as methotrexate or sulfasalazine are not effective, …” ([SP0146] NON ANTI-TNF BIOLOGICS IN AXIAL SPONDYLOARTHRITIS J. Sieper. Med Depart I, Rheumatology, Charite, Berlin, Germany). A study by X. Baraliakos and colleagues agrees with this, though the study looked primarily at disease duration and reatment response (X. Baraliakos et al.: [AB0861] RELATIONSHIP BETWEEN DISEASE DURATION AND TREATMENT RESPONSE IN PATIENTS WITH ANKYLOSING SPONDYLITIS (AS)). As there have been 30 abstracts, ankylosing spondylitis isn’t a big issue in current research.

Thalidomide – there were three abstracts on thalidomide, none on ankylosing spondylitis.

Tocilizumab – there are 153 abstracts on tocilizumab at the EULAR 2012. J. Sieper and colleagues stated: “Tocilizumab (TCZ) is not effective for the treatment of ankylosing spondylitis (AS) …”. They presented a phase 2 study. J. Braum mentioned tocilizumab in his overview given at the “How to manage 3” session.


[OP0166] TOCILIZUMAB (TCZ) IS NOT EFFECTIVE FOR THE TREATMENT OF ANKYLOSING SPONDYLITIS (AS): RESULTS OF A PHASE 2, INTERNATIONAL, MULTICENTRE, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL
J. Sieper1, B. Porter-Brown2, L. Thompson2, O. Harari2, M. Dougados3. 1Charité Med U, Berlin, Germany; 2Roche, Welwyn, United Kingdom; 3Paris-Descartes U, Paris, France
Conclusions: The study failed to demonstrate the efficacy of TCZ over placebo for the treatment of symptoms of AS, irrespective of baseline CRP level. CRP levels declined with TCZ, suggesting adequate IL-6R blockade. The change in ASDAS-CRP was driven by the decrease in CRP. The safety profile of TCZ in this study was consistent with that seen in RA pts.


All in all it dim view. Let’s face it, for practical use there are TNF-inhibitors and that’s all currently, which can be recommended based on studies.
Where’s certolizumab? I guess somewhere in another universe. There 34 abstracts mentioning certolizumab and one is on spondyloarthritis. S.A. Rodriguez Montero and colleagues: “Almost all patients were in DMARDs therapy, 96.1%, while 100% were treated with TNF blockers: etanercept 52%, infliximab 31.5%, adalimumab 13.4%, golimumab 2.4% and certolizumab 0.8%.” (S.A. Rodriguez Montero et al.: [AB0906] Prevalence and characteristics of coronary disease and cardiovascular risk factors in a cohort of patients with spondyloarthropathies and biologic therapy).
Which means for the time being we can offer etanercept, infliximab, adalimumab, and golimumab to our patients.