Anakinra at the ACR 2012 in Washington

There have been 8 studies at the ACR 2012 in Washington mentioning anakinra (IL-1Ra-Receptor antagonist).

Pascal Zufferey and colleagues presented a study on rotator cuff calcifications (Abstract No. 135): “A Pilot Study of the Efficacy of IL1 Blockade by Anakinra in Acute Calcific Periarthritis of the Rotator Cuff”. Conclusion: This pilot open study suggests that IL-1Ra inhibition may be an interesting therapeutic approach in acute calcific periarthritis, especially in patients who have not responded adequately to NSAIDs.” The debate will be opened if anakinra is better than steroid injection, which has a clear cost advantage.

Mary Bach and colleagues looked at gouty arthritis (Abstract No. 146): “The Treatment of Acute Gouty Arthritis in Complex Hospitalized Patients with Anakinra”. Conclusion: “Anakinra is an effective and safe alternative treatment for acute gouty arthritis in medically complex patients who fail or cannot undergo more conventional therapy.” Up to now I didn’t have a patient, who “cannot undergo a more conventional therapy”. We should focus on how to decide which patients fit into such a categogy.

Other studies looked at TRAPs, FMF, and other fever syndroms as well as juvenile idiopathic arthritis (Abstracts No. 179, 190 [Schnitzler’s Syndrome], 275 [Juvenile Dermatomyositis], 747, 762, 1142, 2021).

Anakinra is mentioned in a poster on relapsing polychondritis (No. 1923). Two patients were treated with anakinra, but the treatment has been inefficient.

Anakinra and pseudo gout (calcium pyrophosphate crystal arthritis) - what has changed since the EULAR 2012? In abstract No. 146 two case reports on pseudo gout and anakinra are mentioned.

Link to the EULAR evaluation: http://rheumatologe.blogspot.de/2012/07/anakinra-and-pseudogout-calcium.html  

Gout and other crystal diseases at the EULAR 2012

Gout and other crystal diseases have been a hot topic at the EULAR meeting 2012 in Berlin.


M. Doherty has given a superb lecture on gout and other crystal diseases. Gout is well understood in pathogeneis and can even be cured. The pathogenesis of calcium pyrophosphate (CPP) or basic calcium phosphate (BCP) crystal associated diseases is less well understood. For acut gout or pseudo-gout (CPP) best practice "is to aspirate and inject the joint with corticosteroid (this is safe, quickly effective and allows confirmation of diagnosis) and then apply ice-packs." Alternatives are: " oral steroid; intramuscular injection of steroid or ACTH; oral colchicine (0.5mg 2-4 times daily); oral NSAID/coxib (with PPI); or IL-1 inhibition using a biologic (e.g. anakinra, canakinumab - though currently not licensed for gout)." I must say, I don´t use intramuscular steroids. Without constructing the prerequisites of a patient, who would be considered for intramuscular steroids, I´d say it´s obsolete. I´ll come back to it later. And I don´t see "many" patients, who would not tolerate low dose colchicine. And M. Doherty mentioned colchicine useful: "Low dose colchicine may be helpful for patients with frequently recurring acute CPP crystal synovitis, with or without OA, but there is no long-term treatment to eliminate CPP crystals." If we can lower urate levels, we can "cure" gout. We can do so with: " allopurinol, febuxostat, sulphinpyrazone and benzbromarone - each has its own advantages and disadvantages." Gout has a lower profile than other forms of arthritis, which is to be addressed. " Successful management requires full patient discussion and explanation concerning gout and its treatment". " The key challenge therefore is to raise the profile of gout and to improve training, interest and knowledge of doctors so they can impart correct information to their patients." All in all time spent on this lecture has been time well spent!



[SP0096] GOUT AND OTHER CRYSTAL DISEASES
M. Doherty. Academic Rheumatology, University of Nottingham, Nottingham, United Kingdom
Citation: Ann Rheum Dis 2012;71(Suppl3):24
Session: How to manage 5




In the next study K. Reiter and colleagues looked at "comparative effectiveness and health economic evaluation of systemic anti-inflammatory therapies for acute gout flares". See for yourself at conclusions and limitations. I see a problem for canakinumab as it is extreme expensive compared to other alternative and moreover it´s off-label.



[FRI0430] COMPARATIVE EFFECTIVENESS AND HEALTH ECONOMIC EVALUATION OF SYSTEMIC ANTI-INFLAMMATORY THERAPIES FOR ACUTE GOUT FLARES
K. Reiter1, E. Krishnan1, J. Goldhaber-Fiebert2. 1Deapartment of Medicine; 2Health Policy, Stanford University, Palo Alto, United States
Conclusions: When priced as an unbranded product, colchicine is cost effective for the treatment of acute gout flare. In the US, where colchicine is sold as a branded product, systemic corticosteroids provide a more cost effective alternative. At current prices, biologic therapy does not provide additional benefits commensurate with the cost.
Limitations: These results apply to patients with gout who do not have absolute contraindications to any of the treatment options, such as allergies to the drugs, advanced liver or renal disease, or heart failure. Our models did not take into account the drug half-life of parenteral corticosteroids. Our assessment of biologic therapy may not be applicable to non-canakinumab therapies currently in development.


The next studies all come from the same set or nearly the same set of authors. The first is by R. Alten and colleagues, who compared canakimumab to intramuscular triamcinolone. Serious adverse events occurred more often in the group of patients treated with canakinumab (8.5% vs. 3.4%). Look for yourself!


[AB1081] EFFICACY AND SAFETY OF CANAKINUMAB VS TRIAMCINOLONE ACETONIDE IN PERSISTENT OR ELDERLY GOUTY ARTHRITIS PATIENTS
R. Alten1, M. Bloch2, T. Bardin3, A. So4, A. Shpilsky5, J.M. Nebesky6, T. Kiechle6, N. Schlesinger7. 1Charité Univ Medicine, Berlin, Germany; 2Holdsworth House Medical Practice, Sydney, Australia; 3Hôpital Lariboisière, Paris, France; 4CHUV, University of Lausanne, Lausanne, Switzerland; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 6Novartis Pharma AG, Basel, Switzerland; 7Umdnj-Rwjms, NJ, United States
Conclusions: Canakinumab provided superior pain relief and reduced the risk of a new flare vs TA in this subgroup of pts with persistent GA or elderly pts with GA. Thus it may represent a treatment alternative given that these pts are at a higher risk of comorbidities and may have more limitations to currently available treatments.


In the next study N. Schlesinger and colleagues studied the "effect of canakinumab vs triamcinolone acetonide for treatment of gouty arthritis in patients who are unable to use NSAIDs and colchicine or with severe gouty arthritis". I wondered where they recruited 312 of 454 patients, who are unable to use NSAIDs and colchicine, but severity does the trick. The authors conclude that canakinumab "may represent a potential treatment alternative for this subpopulation." That would be a large subgroup if defined like the authors did.

[FRI0369] EFFECT OF CANAKINUMAB VS TRIAMCINOLONE ACETONIDE FOR TREATMENT OF GOUTY ARTHRITIS IN PATIENTS WHO ARE UNABLE TO USE NSAIDS AND COLCHICINE OR WITH SEVERE GOUTY ARTHRITIS - POSTER TOURS
N. Schlesinger1, R. Alten2, T. Bardin3, M. Bloch4, A. Shpilsky5, G. Krammer6, T. Kiechle6, A. So7. 1Umdnj-Rwjms, NJ, United States; 2Charité Univ Medicine, Berlin, Germany; 3Hôpital Lariboisière, Paris, France; 4Holdsworth House Medical Practice, Sydney, Australia; 5Novartis Pharmaceuticals Corporation, East Hanover NJ, United States; 6Novartis Pharma AG, Basel; 7CHUV, Univ of Lausanne, Lausanne, Switzerland
Conclusions: Pts unable to use NSAIDs and colchicine or with severe GA when treated with CAN had significantly reduced risk of new flare and better pain relief compared to pts treated with TA. CAN may represent a potential treatment alternative for this subpopulation.


There have been more studies:


[AB1080] EFFECT OF SERUM URATE LEVEL ON PREVENTION OF FLARE IN ACUTE GOUTY ARTHRITIS PATIENTS WITH CANAKINUMAB
P. Sunkureddi1, N. Schlesinger2, T. Kiechle3, A. Shpilsky4, A. So5. 1Clear Lake Rheumatology Center, Texas; 2Umdnj-Rwjms, New Jersey, United States; 3Novartis Pharma AG, Basel, Switzerland; 4Novartis Pharmaceuticals Corporation, East Hanover NJ, United States; 5CHUV, University of Lausanne, Lausanne, Switzerland
Conclusions: Results of this retrospective exploratory analysis show that baseline SU level was not a predictor of new flares in patients receiving anti-inflammatory therapy for acute GA, suggesting that GA severity may be more closely related to the prevention of flare than the baseline SU level.


[FRI0377] EARLY RESPONSE TO TREATMENT IS A SURROGATE MARKER OF FLARE RECURRENCE IN ACUTE GOUTY ARTHRITIS
A. So1, T. Bardin2, M. Bloch3, A. Shpilsky4, T. Kiechle5, N. Schlesinger6. 1CHUV, University of Lausanne, Lausanne, Switzerland; 2Hôpital Lariboisière, Paris, France; 3Holdsworth House Medical Practice, Sydney, Australia; 4Novartis Pharmaceuticals Corporation, New Jersey, United States; 5Novartis Pharma AG, Basel, Switzerland; 6Umdnj-Rwjms, New Jersey, United States
Conclusions: These results demonstrate that a 50% pain reduction by VAS within 7 days of treatment in acute GA pts is associated with delay of new flare and can be used as a surrogate marker of time to new flare.


[FRI0402] TOPHI SPREAD, ACUTE JOINTS AND FLARE FREQUENCY PREDICT REFLARE IN GOUTY ARTHRITIS: A SPATIO-TEMPORAL MODEL
T. Bardin1, R. Alten2, N. Schlesinger3, A. Shpilsky4, T. Kiechle5, A. So6. 1Hôpital Lariboisière, Paris, France; 2Charité Teaching Hospital–Schlosspark-Klinik, Berlin, Germany; 3Umdnj-Rwjms; 4Novartis Pharmaceuticals Corporation, NJ, United States; 5Novartis Pharma AG, Basel; 6CHUV-University of Lausanne, Lausanne, Switzerland
Conclusions: Based on this spatio-temporal model the number of tophi locations, number of joints affected by acute GA, along with the number of flares is predictive of subsequent reflaring in this population of GA patients. Thus, the phenomenon of repeated acute GA is impacted mainly by the extent of advanced GA, i.e. the degree of systemic disease and frequency of flares, and not by factors immediately preceding an inflammation (CRP, urate level, etc.) thought to be contributing to the reflaring.


[AB1077] THE SPREAD OF TOPHACEOUS DISEASE STRONGLY PREDICTS TIME TO NEW FLARE IN GOUTY ARTHRITIS
N. Schlesinger1, P. Sunkureddi2, R. Alten3, T. Bardin4, A. Shpilsky5, T. Kiechle6, A. So7. 1Umdnj-Rwjms, NJ; 2Clear Lake Rheumatology Center, Texas, United States; 3Charité Teaching Hospital–Schlosspark-Klinik, Berlin, Germany; 4Hôpital Lariboisière, Paris, France; 5Novartis Pharmaceuticals Corporation, NJ, United States; 6Novartis Pharma AG, Basel; 7CHUV, University of Lausanne, Lausanne, Switzerland
Conclusions: Our results suggest that the number of locations to which tophaceous formations have spread throughout the body leading to systemic disease is an indicator of disease severity in GA. This quantitative measure is a strong predictor of delay of new flare (the higher the number of locations the less delay in reflares).


To me it looks like a massive attack to push forward the use of canakinumab in gouty attacks. Let´s stay alerted if our definitions of intolerability of certrain drugs or disease severity change!

Anakinra and Pseudogout (calcium pyrophosphate crystal arthritis) at the EULAR 2012

As the IL-1Ra-Receptor antagonist anakinra hasn’t been a success story in rheumatoid arthritis, the producer has been looking for alternative targets. Calcium pyrophosphate crystal arthritis is one of these targets. I doubt that calcium pyrophosphate crystal arthritis really is an issue. Most patients do fine on NSAIDs, colchicine, oral and/or local corticosteroids. No wonder the study has only n=16.


S. Ottaviani and colleagues looked at the efficacy of anakinra in calcium pyrophosphate crystal arthritis. It is a multi center retrospective study with five centers involved. Only 16 patients were enrolled in the study. Not all patients had a CPP crystal demonstration in synovial fluid, but only X-ray evidence. Anakinra has been effective, but one patient suffered from pyocyanic pneumonitis.


[FRI0400] EFFICACY OF ANAKINRA IN CALCIUM PYROPHOSPHATE CRYSTAL ARTHRITIS
S. Ottaviani1, L. Brunier1, J. Sibilia2, F. Maurier3, K. Dawidowicz1, E. Palazzo1, G. Hayem1, M. Ardizzone4, D. Wendling5, O. Meyer1, P. Dieudé1. 1Rheumatology, Hôpital Bichat, Paris; 2Rheumatology, CHU Strasbourg-Hautepierre, Strabourg; 3Internal Medicine, CH Metz, Metz; 4Rheumatology, CH Mulhouse, Mulhouse; 5Rheumatology, Hôpital Jean Minjoz, Besançon, France
Conclusions: Anakinra is an effective and relatively well-tolerated treatment of refractory CPP arthritis and should be an alternative in individuals having non-response or contra-indication to conventional therapies.


Maybe there will be the one patients with a decade, where I could imagine prescribing anakinra, but still it would be off-label.