Canakinumab

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An anti-human IL-1β recombinant antibody that can be expected to modulate the immune response in a wide range of acute and chronic conditions. It is used to treat:

It also appears to be effective in Schnitzler's syndrome[7]

It causes marked and rapid improvement in acute symptoms of the above, not all of whom it may be licensed for. C-reactive protein and serum amyloid A levels are reduced in many of the above conditions.

Contents

Potential

It can be expected to suppress the acute inflammatory response in almost any condition, such as gout so has tended to be tried where other therapies fail and side effect profile might be acceptible. In particular it should not be used when active infection is suspected in the differential diagnosis. It is probably not associated with increased risk of macrophage activation syndrome but risk of malignancy induction less clear. Preliminary evidence from long term studies suggest reductions in cardiovascular disease and cancer incidence which means it may be useful in conditions associated with low degree chronic activation of the acute inflammatory response such as post myocardial infarction[8]. However in the context of current marketing and pricing strategies for the medication and the need to minimise the risk of secondary infection such indications are unlikely to make commercial or cost effective sense.

Cautions

  • Discontinue treatment if patient develops a serious infection.
  • Test for latent tuberculosis
  • Effectively an immunosuppressant
  • Concomitant use with tumour necrosis factor (TNF) inhibitors

Contraindications

  • Active infection
  • Live vaccination
  • Anti-TNF drugs

Side effects

Pharmacology

It binds IL-1β so preventing its interaction with cell surface receptors.

References

  1. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN. Use of canakinumab in the cryopyrin-associated periodic syndrome. The New England journal of medicine. 2009 Jun 4; 360(23):2416-25.(Link to article – subscription may be required.)
  2. Kone-Paut I, Quartier P, Fain O, Grateau G, Pillet P, Le Blay P, Bonnet F, Despert V, Stojanovic KS, Willemin L, Quéré S, Reigneau O, Hachulla E. Real-world experience and impact of canakinumab in cryopyrin-associated periodic syndrome: Results from the French observational study ENVOL. Arthritis care & research. 2016 Sep 16.(Epub ahead of print) (Link to article – subscription may be required.)
  3. Ruperto N, Brunner HI, Quartier P, Constantin T, Wulffraat N, Horneff G, Brik R, McCann L, Kasapcopur O, Rutkowska-Sak L, Schneider R, Berkun Y, Calvo I, Erguven M, Goffin L, Hofer M, Kallinich T, Oliveira SK, Uziel Y, Viola S, Nistala K, Wouters C, Cimaz R, Ferrandiz MA, Flato B, Gamir ML, Kone-Paut I, Grom A, Magnusson B, Ozen S, Sztajnbok F, Lheritier K, Abrams K, Kim D, Martini A, Lovell DJ. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. The New England journal of medicine. 2012 Dec 20; 367(25):2396-406.(Link to article – subscription may be required.)
  4. Barranco C. Therapy: Patients with TRAPS respond to canakinumab. Nature reviews. Rheumatology. 2016 Aug; 12(8):436.(Link to article – subscription may be required.)
  5. Kostjukovits S, Kalliokoski L, Antila K, Korppi M. Treatment of hyperimmunoglobulinemia D syndrome with biologics in children: review of the literature and Finnish experience. European journal of pediatrics. 2015 Jun; 174(6):707-14.(Link to article – subscription may be required.)
  6. Sozeri B, Gulez N, Ergin M, Serdaroglu E. The experience of canakinumab in renal amyloidosis secondary to Familial Mediterranean fever. Molecular and cellular pediatrics. 2016 Dec; 3(1):33.(Link to article – subscription may be required.)
  7. Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, Church MK, Maurer M. Efficacy and safety of canakinumab in Schnitzler's syndrome: a multi-center randomized placebo-controlled study. The Journal of allergy and clinical immunology. 2016 Sep 19.(Epub ahead of print) (Link to article – subscription may be required.)
  8. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. August 27, 2017 DOI: 10.1056/NEJMoa1707914 accessed 28 August 2017