This is autoinflammation in RA

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease caused by a combination of genetic and environmental factors which primarily affects the joints.1 RA is estimated to affect 0.5–1% of the worldwide population, although variation in prevalence has been reported across geographies and ethnicities.1 The aim of RA treatment is to achieve remission or minimal disease activity, using a treat to target approach.2,3

European Alliance of Associations for Rheumatology (EULAR) and American Colleague of Rheumatology (ACR) consider methotrexate to be the ‘anchor’ drug in RA, either as monotherapy (first-line DMARD) or in combination with other drugs (glucocorticoids, other csDMARDs, bDMARDs, or tsDMARDs).2,3

of patients treated with b/tsDMARDS meet the EULAR criteria for difficult-to-treat RA in real-world studies4-6

The EULAR definition of difficult-to-treat requires presence of three criteria: failure of ≥2 b/ts DMARDs (different MoA), signs of active/progressive disease, and perception by the rheumatologist and/or patient that disease management has become problematic.

EULAR definition of difficult-to-treat RA7

All three of the following criteria need to be present:

  • Treatment according to EULAR recommendation and failure of ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless contraindicated)
  • Signs suggestive of active/progressive disease, defined as ≥1 of
    • At least moderate disease activity (according to validated composite measures including joint counts, for example, DAS28-ESR>3.2 or CDAI>10).
    • Signs (including acute phase reactants and imaging) and/or symptoms suggestive of active disease (joint related or other).
    • Inability to taper glucocorticoid treatment (below 7.5 mg/day prednisone or equivalent).
    • Rapid radiographic progression (with or without signs of active disease)
    • Well-controlled disease according to above standards, but still having RA symptoms that are causing a reduction in quality of life.
  • The management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient.

Why some RA patients don’t respond to conventional therapies

Though RA is primarily defined as an autoimmune disease, patients with difficult-to- treat RA may have a pronounced autoinflammatory component to their disease. If your patient has tried and failed multiple RA treatments, their disease may be driven by autoinflammation. Interleukin-1 (IL-1) may be a driver of that inflammation.8,9

Adapted from: Figure 1, McGonagle, et al. Mechanistic immunological based classification of rheumatoid arthritis.

Identifying autoinflammation in RA

A few general criteria may provide important context for identifying if any of your patients have predominantly autoinflammatory RA.

efficacy in rheumatoid arthritis (ra)

When may Kineret be the right treatment for patients with RA?

Kineret is a valuable asset for the treatment of refractory RA.13 Kineret blocks the interleukin-1 (IL-1) receptor to help protect against autoinflammatory events.11

The safety and efficacy of anakinra in combination with methotrexate have been demonstrated in 1790 RA patients ≥ 18 years of age with varying degrees of disease severity.11

Kineret is indicated in adults for the treatment of the signs and symptoms of RA in combination with methotrexate, with an inadequate response to methotrexate alone. A clinical response to anakinra generally appears within 2 weeks of initiation of treatment and is sustained with continued administration of anakinra. Maximal clinical response is generally seen within 12 weeks after starting treatment.11

Kineret was studied in patients with active RA
This randimised, double-blind, placebo-controlled trial was conducted on 899 patients with active RA who had been on a stable dose of methotrexate (10-25 mg/ week) for at least 8 weeks. Patients were randomised to Kineret (n=250) or placebo (n=251) in addition to their stable doses of methotrexate. The first 501 patients were evaluated for signs and symptoms of active RA.14

At month 6, ~1 in 4 patients achieved a minimum of ACR50 (23%)* following treatment with Kineret compared to placebo (10%).14

Adapted from: Figure 1 A, Cohen et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate

Radiographic changes improved over the course of 1 year with Kineret
The effect of Kineret on the progression of structural damage was assessed by measuring the change from baseline at month 12 in the Total Modified Sharp Score (TMSS) and its subcomponents, erosion score (ES), and joint space narrowing (JSN) score. Radiographs of hands/wrists and forefeet were obtained at baseline, 6 months, and 12 months and scored by readers who were unaware of treatment group. Differences between placebo and Kineret for change in TMSS, ES, and JSN score were observed at 12 months.14

The disability index of the Health Assessment Questionnaire (HAQ) was administered monthly for the first 6 months and quarterly thereafter during the study.14

Health outcomes were assessed by the Short Form-36 (SF-36) questionnaire. The 1-year data on HAQ in Study 1 showed more improvement with Kineret than placebo. The physical component summary score of SF-36 also showed more improvement with Kineret than placebo but not the mental component summary.14

Adapted from: Table 5, Kineret US Prescribing information

Abbreviations
csDMARD, conventional synthetic disease-modifying antirheumatic drug; bDMARD, biologic disease-modifying antirheumatic drug; tsDMARD, targeted synthetic disease-modifying antirheumatic drug; TNF, tumor necrosis factor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; MTX, methotrexate.

Kineret Q&A

How is Kineret administered?
  • Kineret is given in a pre-filled syringe containing 100 mg of anakinra per 0.67 ml (150 mg/ml).1
  • Kineret is given as a subcutaneous injection.1
  • Dosage depends on indication. In children, the dose is determined depending on body weight. Please refer to current SmPC.
How should Kineret be stored?
  • Kineret should be stored in a refrigerator between 2°C and 8°C.1
  • Kineret should not be frozen or shaken.1
  • Kineret should be kept in its original carton and away from light.1

References

  • Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, Kavanaugh A, McInnes IB, Solomon DH, Strand V, Yamamoto K. Rheumatoid arthritis. Nat Rev Dis Primers. 2018 Feb 8;4:18001. doi: 10.1038/nrdp.2018.1. PMID: 29417936.
  • Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, Caporali R, Edwards CJ, Hyrich KL, Pope JE, de Souza S, Stamm TA, Takeuchi T, Verschueren P, Winthrop KL, Balsa A, Bathon JM, Buch MH, Burmester GR, Buttgereit F, Cardiel MH, Chatzidionysiou K, Codreanu C, Cutolo M, den Broeder AA, El Aoufy K, Finckh A, Fonseca JE, Gottenberg JE, Haavardsholm EA, Iagnocco A, Lauper K, Li Z, McInnes IB, Mysler EF, Nash P, Poor G, Ristic GG, Rivellese F, Rubbert-Roth A, Schulze-Koops H, Stoilov N, Strangfeld A, van der Helm-van Mil A, van Duuren E, Vliet Vlieland TPM, Westhovens R, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):3-18. doi: 10.1136/ard-2022-223356. Epub 2022 Nov 10. Erratum in: Ann Rheum Dis. 2023 Mar;82(3):e76. doi: 10.1136/ard-2022-223356corr1. PMID: 36357155.
  • Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021 Jul;73(7):924-939. doi: 10.1002/acr.24596. Epub 2021 Jun 8. PMID: 34101387; PMCID: PMC9273041.
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  • Nagy G, Roodenrijs NMT, Welsing PM, Kedves M, Hamar A, van der Goes MC, Kent A, Bakkers M, Blaas E, Senolt L, Szekanecz Z, Choy E, Dougados M, Jacobs JW, Geenen R, Bijlsma HW, Zink A, Aletaha D, Schoneveld L, van Riel P, Gutermann L, Prior Y, Nikiphorou E, Ferraccioli G, Schett G, Hyrich KL, Mueller-Ladner U, Buch MH, McInnes IB, van der Heijde D, van Laar JM. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35. doi: 10.1136/annrheumdis-2020-217344. Epub 2020 Oct 1. PMID: 33004335; PMCID: PMC7788062.
  • Savic S, Mistry A, Wilson AG, Barcenas-Morales G, Doffinger R, Emery P, McGonagle D. Autoimmune-autoinflammatory rheumatoid arthritis overlaps: a rare but potentially important subgroup of diseases. RMD Open. 2017 Nov 1;3(2):e000550. doi: 10.1136/ rmdopen-2017-000550. PMID: 29177082; PMCID: PMC5687541.
  • McGonagle D, Watad A, Savic S. Mechanistic immunological based classification of rheumatoid arthritis. Autoimmun Rev. 2018 Nov;17(11):1115-1123. doi: 10.1016/j.autrev.2018.06.001. Epub 2018 Sep 11. PMID: 30213700.
  • Vela P. Extra-articular manifestations of rheumatoid arthritis, now. Eur Med J Rheumatol. 2014;1:103-112
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  • Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR, Furst DE, Parks D, Kavanaugh A, O'Dell J, King C, Leong A, Matteson EL, Schousboe JT, Drevlow B, Ginsberg S, Grober J, St Clair EW, Tindall E, Miller AS, McAlindon T. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Jan;68(1):1-26. doi: 10.1002/art.39480. Epub 2015 Nov 6. PMID: 26545940.
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