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.