Otezla® and an increased risk of suicide

Otezla® (active ingredient: Apremilast from Celgene) has been given a "Red Hand Letter" this month. In a "red hand letter" all physicians in Germany get important communications about a drug (e.g. new discovered side effects of a drug).

In the summary the letter reads: "Occasional cases of suicidal thoughts and suicidal behavior (with or without history of depression) have been reported in clinical trials and after market introduction (frequency ≥1/1,000 to ≤1/100). Cases of successful suicide have been reported after market introduction in patients treated with Apremilast."

The following background information has been given: "Notes on suicide thoughts and suicide behaviors: - The data collected after market launch by 20^th March 2016 included 65 reported cases with 5 suicides completed, 4 suicide trials, 50 cases with suicide thoughts, 5 cases with depression and suicide thoughts, and 1 case with suicidal behavior. (...)"

Perhaps I’m too skeptical about small molecules, but I had argued already years ago that a change in communication within the cell could lead to more problems in regard to side effects than the interruption of communication between cells (e.g. by biologics). For the biologics used up to date in rheumatology, I do not know an increase in suicide and suicidal ideation; however, Amgen had withdrawn from the development of brodalumab (anti-IL-17R autoantibody). Brodalumab will be available in the US as Siliq, an introduction to Europe is expected for the first quarter of 2017. More about this has been discussed in the psoriasis network (in German!). For Tofacitinib, two suicides were listed in 2012, "ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS". For baricitinib the number of patients tested may still be too low to answer this question.

I have used Otezla® very rarely since I have preferred other drugs, which were approved earlier, because of better knowledge and more experience. I won’t change this attitude. On the other hand, a danger that is known is also a lesser danger. 

Links (some texts in German):
Psoriasis-Netz zu Brodalumab http://www.psoriasis-netz.de/lexikon/brodalumab-siliq 
ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS im Jahr 2012 - http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM302960 http://rheumatologe.blogspot.de/2015/11/brodalumab-at-acr-2015-meeting-in-san.html 
http://rheumatologe.blogspot.de/2013/01/neue-therapien-bei-rheumatoider.html 
http://rheumatologe.blogspot.de/2016/08/protein-kinase-inhibitors-small.html

.

Otezla® und ein erhöhtes Risiko für Selbstmord

Zu Otezla® (Wirkstoff: Apremilast der Firma Celgene) hat es diesen Monat einen „Rote Hand Brief“ gegeben. In einem „Rote Hand Brief“ bekommen alle Ärzte wichtige Mitteilung zu einem Medikament.

In der Zusammenfassung steht nun:„Gelegentliche Fälle von Suizidgedanken und suizidalem Verhalten (mit oder ohne Depression in der Anamnese) wurden in klinischen Studien und nach Markteinführung berichtet (Häufigkeit ≥1/1.000 bis ≤1/100). Fälle von vollendetem Suizid wurden nach Markteinführung bei Patienten, die mit Apremilast behandelt wurden, berichtet.“

Folgende Hintergrundinformationen wurden u.a. gegeben: „Hinweise bezüglich Suizidgedanken und Suizidverhalten: 
- Die nach Markteinführung bis zum 20. März 2016 erhobenen Daten umfassten 65 gemeldete Fälle mit folgender Verteilung: 5 vollendete Suizide, 4 Suizidversuche, 50 Fälle mit Suizidgedanken, 5 Fälle mit Depression und Suizidgedanken sowie 1 Fall mit suizidalem Verhalten. (…)“

Vielleicht verhalte ich mich gegenüber den small molecules zu skeptisch, aber ich habe schon vor Jahren die Meinung vertreten, dass eine Veränderung der Kommunikation innerhalb der Zelle mehr Probleme in Hinsicht auf unerwünschte Arzneimittelwirkungen nach sich ziehen könnte als die Unterbrechung der Kommunikation der Zellen untereinander (z.B. durch Biologika). Für die die bislang in der Rheumatologie eingesetzten Biologika ist mir eine Erhöhung von Suizid und Suizidgedanken nicht bekannt; allerdings hatte sich Amgen aus der Entwicklung von Brodalumab (anti-IL-17R Autoantikörper) zurückgezogen. Brodalumab wird als Siliq in den USA erhältlich sein, eine Einführung in Europa wird für das 1. Quartal 2017 erwartet. Mehr dazu im Psoriasis-Netz. Für Tofacitinib wurden zwei Suizide im Schreiben „ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS” im Jahr 2012 aufgelistet. Für Baricitinib kann die Zahl der getesteten Patienten für diese Frage noch zu gering sein.

Ich habe Otezla® erst sehr selten eingesetzt, da ich andere Medikamente, die früher zugelassen wurden, durch besseres Wissen und mehr Erfahrung bevorzugt habe. Daran wird sich zunächst auch nichts ändern. Andererseits ist eine Gefahr, die bekannt ist, auch eine geringere Gefahr.
Link:
Psoriasis-Netz zu Brodalumab http://www.psoriasis-netz.de/lexikon/brodalumab-siliq 
ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS im Jahr 2012 - http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM302960 http://rheumatologe.blogspot.de/2015/11/brodalumab-at-acr-2015-meeting-in-san.html 
http://rheumatologe.blogspot.de/2013/01/neue-therapien-bei-rheumatoider.html 
http://rheumatologe.blogspot.de/2016/08/protein-kinase-inhibitors-small.html

.

 

Otezla® und die IQWIG Einschätzung

Das Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) hat Otezla® (Wirkstoff: Apremilast der Firma Celgene) keinen Zusatznutzen gegenüber zweckmäßigen Vergleichstherapien zuerkennen können. Was heißt das für Patienten mit Psoriasisarthritis?

Der Gemeinsame Bundesausschuss (GBA) legte für Patienten mit aktiver Psoriasis-Arthritis als zweckmäßige Vergleichstherapien dien Therapie mit einem Tumor-Nekrose-Faktor(TNF)-alpha-Inhibitor (TNFi)wie Adalimumab, Etanercept, Golimumab oder Infliximab, gegebenenfalls auch in Kombination mit Methotrexat (MTX) fest. Die vom Hersteller vorgelegten Dossiers enthielten dazu jedoch keine Daten. Interessanterweise hat der Hersteller auch keine Zusatznutzen beantragt – weder für die Psoriasisarthritis noch für die mittelschwere bis schwere Plaque-Psoriasis.

Otezla® ist zugelassen und kann verordnet werden. Es wird nur um den Preis gestritten. TNFi kosten im Jahr etwas über 20.000 €, Otezla® wird mit etwa 17.000 € zu veranschlagen sein, allerdings kommt man bei MTX mit unter 1100 € Jahreskosten aus.

Wir haben Patienten, die Otezla® benötigen. Und denen darf das Medikament auch verordnet werden. Aber wir werden selbstverständlich auf die Einschätzung des GBA warten.

Link:

Kein Zusatznutzen für Otezla – was heißt das? http://www.psoriasis-netz.de/medikamente/apremilast-otezla/kein-zusatznutzen-fuer-otezla-was-heisst-das.html

Otezla approved in Europe for the treatment of psoriatic arthritis

Roughly, it has taken a year for Otezla (Apremilast) to be approved in Europe. I’ve written about Otezla before: http://rheumatologe.blogspot.de/2014/03/fda-approval-for-apremilast-otezla-in.html. And I’ve also written on Otezla yesterday (in German) because Celgene supplied me with the fact sheet on Otezla: http://rheumatologe.blogspot.de/2015/02/otezla-bei-psoriasisarthritis.html.

Otezla is available on prescription in rheumatology "as monotherapy or in combination with disease-modifying anti-rheumatic drugs (DMARDs ) for the treatment of active psoriatic arthritis (PsA ) in adult patients who have an inadequate response to previous DMARD therapy or are intolerant to this therapy". EMEA decided to approve the drug according to the PALACE 1-3 studies, which had observed about 1500 patients. More patients achieved a significantly higher ACR20 response in comparison to placebo (after 16 weeks). There was a reduction in the number of swollen and painful joints. Other improvements included dactylitis , enthesitis , quality of life etc.; and not to forget skin involvement of psoriasis. Most frequent adverse events were: diarrhea, nausea, upper respiratory tract infections.

Did I desperately wait for Otezla to be approved? Yes and no. There are not as many patients as in rheumatoid arthritis, which is one factor that there aren’t as many studies as in rheumatoid. There is a lack of DMARDs, what works in rheumatoid doesn’t have to work in psoriatic arthritis. Some rheumatologists too eagerly diagnose psoriatic arthritis, which made me doubt the diagnosis if not made by myself – and I even doubt myself and review the diagnosis. The lack of DMARDs for the treatment of psoriatic arthritis results in a yes for Otezla. But I have to admit that I don’t have a patient, where I would try it right now. How come will you ask. That’s easy to answer. Ustekinumab (Stelara) isn’t on the market so long that I’d seen enough patients to fail, so I'm not in need of a next drug. Actually I’m still working out the place of Stelara under real life conditions.

To sum it up: I’m happy to have the option to prescribe Otezla, but I’m uncertain about when I’ll have to prescribe it.

25.02.2015:
I've looked at the PASI 90 percentages in the ESTEEM 1 and 2 studies - less than 10% of patients on apremilast achieved a PASI 90, which is defenitely less than 45% of patients on ustekinumab, who achieved a PASI 90 (ACCEPT).
The price level is still uncertain in Germany; I've just been told 17,000 € per year. And I've seen around 22,000-23,000 US$ for the US. The price levels are too high for a small molecule.

FDA Approval for Apremilast (Otezla) in Patients with Psoriatic Arthritis (PsA)

The FDA has approved apremilast (Otezla) to treat adult patients with active psoriatic arthritis (PsA). The currently approved DMARDs include biologics like THN-alpha-inhibitors and an IL-12/IL-23 inhibitor (ustekinumab).

The safety and effectiveness of apremilast (Otezla), a phosphodieasterase-4-inhibitor (PDE-4), were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with apremilast (Otezla) showed improvement in signs and symptoms of PsA compared to placebo. Link: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm390091.htm

There has been a study by Arthur Kavanaugh and colleagues (Abstract No. L13) at the 2012 ACR Meeting in Washington: “Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results of a Phase 3, Randomized, Controlled Trial”. Conclusion: “Apremilast significantly improved signs and symptoms of PsA and resulted in statistically and clinically meaningful improvements in physical function. Apremilast was generally well tolerated and no new safety or laboratory signals were detected.” Lets look at some side effects: diarrhea (placebo: 2.4%; apremilast 20 mg BID: 11.3%; and apremilast 30 mg BID, 19.0%), nausea (high dose: 18.5%), headache (10.1%, and 10.7%), and more.

At the 2013 ACR Meeting in San Diego we saw even more studies.

C.J. Edwards and colleagues presented the following study [Abstract No. 311]: “Long-Term (52-Week) Results Of a Phase 3, Randomized, Controlled Trial Of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis and Current Skin Involvement (PALACE 3).” Conclusion: “Over 52 wks, APR continued to demonstrate efficacy in the treatment of PsA and associated psoriasis, including clinically meaningful improvements in signs and symptoms and physical function. APR demonstrated an acceptable safety profile with up to 52 wks of treatment and was generally well tolerated.”

M. Cutolo and colleagues presented the following study [Abstract No. 317]: “Apremilast, An Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-Term (52-Week) Improvement In Tender and Swollen Joint Counts In Patients With Psoriatic Arthritis: Results From Three Phase 3, Randomized, Controlled Trials.” Conclusion: “Over 52 wks, APR continued to demonstrate efficacy in the treatment of PsA, including clinically meaningful improvements in SJC and TJC. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.”

G. Schett and colleagues presented the following study [Abstract No. 331]: “Apremilast, An Oral Phosphodiesterase 4 Inhibitor, Is Associated With Long-Term (52-Week) Improvement In Physical Function In Patients With Psoriatic Arthritis: Results From Three Phase 3, Randomized, Controlled Trials.” Conclusion: “Over 52 wks, APR continued to demonstrate meaningful clinical response in PsA pts, including measures of physical function. APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks.”

There were some more studies shown at the  ACR 2013 Meeting in San Diego, for long-term safety look at the following study.

A. Kavanaugh and colleagues presented the following study [Abstract No. 310]: “ Long-Term Safety and Tolerability Of Apremilast, An Oral Phosphodiesterase 4 Inhibitor, In Patients With Psoriatic Arthritis: Pooled Safety Analysis Of Three Phase 3, Randomized, Controlled Trials.” Conclusion: “APR demonstrated an acceptable safety profile and was generally well tolerated for up to 52 wks with no new safety concerns identified with long-term exposure. These data do not indicate a need for laboratory monitoring.”

We now must look, which group of patients really benefits from the new drug. We must compare efficacy and costs in everyday life. And we still need some head to head evaluation against established biologics. How about radiographic changes erosions as well as proliferations? Still some work to be done and still a long way to go, but

Welcome Otezla!

There sure are patients waiting for you! And hopefully Otezla will get EMEA approval soon.

Apremilast in Ankylosing Spondylitis

I had been interested in apremilast in psoriatic and rheumatoid athritis. Now, there’s a new development: apremilast is tested for treatment of ankylosing spondylitis. Apremilast is an oral phosphodiesterase 4 inhibitor (PDE-4), which modulates inflammatory mediators.

E. Pathan and colleagues “just” published a study with the title: “Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis”. They concluded: “Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.” But if you look at the result part, you get disenchanted: “Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance.” CRP didn’t change, no difference between verum and placebo groups. The data might also suggest stopping further testing.

The authors argue to conduct a suitably powered study, because of the “current lack of effective oral DMARDs in AS”.

I’m happy that I don’t have to decide as I’m sceptical about apremilast in treating ankylosing spondylitis. Maybe apremilast will be useful against psoriatic arthritis, so it won’t be the last we hear on apremilast, but that’s another story.

Links:

Psoriatic Arthritis: http://rheumatologe.blogspot.de/2012/12/psoriatic-arthritis-at-acr-2012-in.html

Rheumatoid Arthritis and others: http://rheumatologe.blogspot.de/2012/01/efficacy-and-safety-of-apremilast-oral.html

Ankylosing Spondylitis: http://www.ncbi.nlm.nih.gov/pubmed/22984171  

Psoriatic Arthritis at the ACR 2012 in Washington

Non-anti-TNF Biologics in Psoriatic Arthritis at EULAR 2011. http://rheumatologe.blogspot.de/2012/07/non-anti-tnf-biologics-in-psoriatic.html. I hope for new results on new drugs as therapy for psoriatic arthritis still lags behind.

Actually I’ve found only data on one drug: apremilast. Apremilast is a small molecule – a phospodiesterase 4 inhibitor. About a year ago, I’ve mentioned apremilast in ankylosing spondylitis: http://rheumatologe.blogspot.de/2012/01/efficacy-and-safety-of-apremilast-oral.html.

Juergen Rech and colleagues presented (Abstract No 272): “Interim Safety Analysis of a Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy Study of Apremilast (CC10004) in Subjects with Erosive Hand Osteoarthritis.” Conclusion: “ … we conclude that apremilast may also be well tolerated in patients with EHOA [erosive hand arthritis]. Apremilast, if proven to be efficacious in ongoing investigations, will be an interesting treatment option for patients with EHOA.”

There has been a second study by Arthur Kavanaugh and colleagues (Abstract No. L13): “Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results of a Phase 3, Randomized, Controlled Trial”. Conclusion: “Apremilast significantly improved signs and symptoms of PsA and resulted in statistically and clinically meaningful improvements in physical function. Apremilast was generally well tolerated and no new safety or laboratory signals were detected.” Lets look at some side effects: diarrhea (placebo: 2.4%; apremilast 20 mg BID: 11.3%; and apremilast 30 mg BID, 19.0%), nausea (high dose: 18.5%), headache (10.1%, and 10.7%), and more.

There are still some hurdles to be taken by apremilast!

There’s another study of Bremander on smoking. B. I. Bremander and colleagues presented: "Smoking Is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish Population Based Cohort of Patients with Psoriatic Arthritis" (Abstract No. 1828). Conclusion: In this population based PsA cohort, patients who were ever smokers reported worse clinical outcomes compared with never smokers. ..."

I think the message is clear. Stop smoking!

Studies on ustekinumab are here: http://rheumatologe.blogspot.de/2012/12/ustekinumab-at-acr-2012-in-washington.html.

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.