A Comprehensive Pharmacological and Clinical Monograph on Canakinumab (Ilaris®)

I. Introduction and Executive Summary

Canakinumab is a high-affinity, fully human monoclonal antibody of the IgG1/κ isotype subclass, meticulously engineered to selectively target and neutralize the pro-inflammatory cytokine, human interleukin-1β (IL-1β).[1] Marketed by Novartis under the brand name Ilaris®, this biotech therapeutic represents a significant milestone in the field of targeted immunotherapy.[1] Its clinical development and application have established a dual identity for the molecule. Firstly, it serves as an indispensable, transformative therapy for a portfolio of rare and severe autoinflammatory diseases characterized by dysregulated IL-1β production. Secondly, it has functioned as a pivotal investigational agent, providing the first large-scale, proof-of-concept validation for the inflammatory hypothesis of atherosclerosis.[1]

The therapeutic utility of canakinumab is rooted in its highly specific mechanism of action, which interrupts a key inflammatory cascade at its source. This precision is complemented by a favorable pharmacokinetic profile, most notably a long elimination half-life that permits infrequent subcutaneous dosing, a critical factor for adherence and quality of life in patients with chronic conditions.[1] Across its approved indications—spanning a range of Periodic Fever Syndromes, Still's disease, and refractory gout flares—canakinumab has demonstrated robust and sustained efficacy in well-controlled clinical trials. Its safety profile is consistent and predictable, primarily defined by an on-target increased risk of infection, which necessitates careful patient selection and monitoring.[12]

However, the clinical narrative of canakinumab is inextricably linked to its economic profile. The drug's development journey illuminates its value not only as a therapeutic agent but also as a scientific instrument. Its initial success in rare monogenic diseases like Cryopyrin-Associated Periodic Syndromes (CAPS) provided a clear validation of IL-1β as a pathogenic driver.[9] This understanding was then leveraged to investigate its role in more common, complex diseases. The landmark Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) applied this targeted anti-inflammatory strategy to post-myocardial infarction patients, yielding the first definitive evidence that inhibiting inflammation, independent of lipid-lowering, reduces cardiovascular events.[10] This effectively transformed canakinumab into a "molecular probe," using insights from rare genetic disorders to validate a fundamental pathogenic mechanism in one of the world's most prevalent chronic diseases.

This success also exposed a fundamental challenge in modern drug development and healthcare economics: a "price-indication paradox." The high price of canakinumab, established based on its profound value in treating debilitating orphan diseases with no other options, renders it economically unviable for widespread use in a common condition like post-myocardial infarction risk reduction, despite its proven clinical efficacy.[15] This report provides an exhaustive analysis of canakinumab, synthesizing its molecular attributes, pharmacological profile, pivotal clinical data, regulatory history, and its complex position within the global therapeutic and economic landscape.

II. Molecular Profile and Pharmacology

Structural and Physicochemical Properties

Canakinumab is a biologic therapeutic product, classified as a recombinant, fully human monoclonal antibody.[1] It belongs to the IgG1/κ isotype subclass and is categorized pharmacologically as an Interleukin Antagonist and an Immunosuppressive Agent.[1]

The molecule is a large protein with a deglycosylated molecular mass of approximately 145 kDa.[2] It is composed of two identical heavy chains, each comprising 447 or 448 amino acid residues, and two identical light chains of the kappa subtype, each with 214 residues.[2] As is characteristic of IgG1 antibodies, both heavy chains of canakinumab contain a conserved N-linked glycosylation site at asparagine 298 (Asn298), where complex oligosaccharide chains are attached.[1] This glycosylation is critical for maintaining the structural integrity of the Fc region and modulating its effector functions and pharmacokinetic stability.

Canakinumab is produced in a murine Sp2/0-Ag14 cell line and is supplied for clinical use either as a white, preservative-free, lyophilized powder requiring reconstitution with Sterile Water for Injection, or as a sterile, ready-to-use solution.[2] The final formulation contains excipients such as L-histidine (as a buffer), sucrose or mannitol (as stabilizers), and polysorbate 80 (as a surfactant to prevent aggregation), ensuring the stability and solubility of the antibody for subcutaneous administration.[2]

Table 1: Canakinumab Drug Profile Summary

Characteristic	Description
Generic Name	Canakinumab 1
Brand Name	Ilaris® 1
DrugBank ID	DB06168 1
CAS Number	914613-48-2
Drug Class	Monoclonal Antibodies, Antineoplastics; Immunosuppressive Agents; Interleukin Antagonists 1
Mechanism of Action	High-affinity binding and neutralization of human interleukin-1β (IL-1β) 3
Molecular Target	Interleukin-1 beta (IL-1β) 1
Structure	Recombinant human IgG1/κ monoclonal antibody; approx. 145 kDa 2
Formulation	Lyophilized powder for reconstitution or solution for injection 2
Route of Administration	Subcutaneous injection 7

Mechanism of Action

The therapeutic effect of canakinumab is derived from its highly specific and potent antagonism of IL-1β, a key cytokine in the innate immune system that drives inflammatory responses.[3]

Target Specificity and Neutralization

Canakinumab binds with high affinity to the soluble, biologically active form of human IL-1β.[1] The equilibrium dissociation constant (

KD​), a measure of binding affinity, has been determined by surface plasmon resonance to be approximately 60 pM, indicating a very strong and stable interaction.[11] This binding is exquisitely specific; canakinumab does not cross-react with other members of the IL-1 family, such as IL-1α or the endogenous IL-1 receptor antagonist (IL-1ra).[1] This specificity is a critical feature, as it allows for the targeted neutralization of a single pro-inflammatory pathway while preserving the homeostatic and potentially beneficial roles of related molecules.

By binding to a specific epitope on IL-1β, canakinumab acts as a neutralizing antibody, effectively "masking" the cytokine's receptor-binding domain.[20] This steric hindrance prevents IL-1β from engaging with its cell-surface receptor, the IL-1 receptor type I (IL-1RI). Consequently, the formation of the high-affinity signaling complex, which requires the recruitment of the IL-1 receptor accessory protein (IL-1RAcP), is blocked, and the inflammatory signal is not transduced.[20]

Downstream Signaling Inhibition

The blockade of IL-1RI activation effectively silences the downstream intracellular signaling cascades that are normally initiated by IL-1β. These include two of the most important pathways in inflammation: the Nuclear Factor-kappa B (NF-κB) pathway and the Mitogen-Activated Protein Kinase (MAPK) pathway.[20] NF-κB is a master transcriptional regulator that, upon activation, drives the expression of a wide array of pro-inflammatory genes. By inhibiting this cascade, canakinumab leads to a profound reduction in the production of secondary inflammatory mediators, including other key cytokines like IL-6 and Tumor Necrosis Factor-alpha (TNF-α), as well as various chemokines that recruit immune cells to sites of inflammation.[20] This comprehensive dampening of the inflammatory response is reflected systemically by a rapid and sustained decrease in the levels of acute-phase reactants, such as high-sensitivity C-reactive protein (hsCRP) and Serum Amyloid A (SAA), which serve as reliable pharmacodynamic markers of canakinumab's biological activity.[20]

Pharmacokinetics and Pharmacodynamics

Canakinumab exhibits a pharmacokinetic (PK) profile typical of a human IgG1 monoclonal antibody, characterized by slow absorption, limited distribution, and a long elimination half-life.[11]

• Absorption: Following subcutaneous administration of a 150 mg dose, canakinumab is absorbed slowly from the injection site, with peak serum concentrations (Cmax​) of approximately 16 µg/mL reached after about 7 days (Tmax​).[1] The absolute bioavailability is estimated to be between 66% and 70%, which is consistent with other subcutaneously administered monoclonal antibodies.[1] The incomplete bioavailability is likely due to catabolism by proteolytic enzymes in the lymphatic system during transit from the injection site to systemic circulation.[11] Pharmacokinetic studies have demonstrated that exposure, as measured by the area under the curve (AUC), increases in direct proportion to the administered dose, indicating linear pharmacokinetics.[1]
• Distribution: Canakinumab has a small volume of distribution at steady state (Vss​) of approximately 6.0 L in a typical 70 kg patient.[11] This value is slightly larger than the plasma volume and indicates that the drug is primarily confined to the vascular and interstitial compartments, with minimal penetration into deep tissues, as expected for a large 150 kDa protein.[11]
• Metabolism and Elimination: As a large protein, canakinumab is not eliminated via renal or hepatic pathways in its intact form. Instead, like other endogenous immunoglobulins, it is believed to be cleared through intracellular catabolism.[11] This process involves non-specific fluid-phase or receptor-mediated endocytosis by cells of the reticuloendothelial system, followed by degradation into smaller peptides and amino acids that are then recycled in the body.[11]
• Elimination Half-Life: The most clinically significant pharmacokinetic feature of canakinumab is its long terminal elimination half-life, which averages approximately 26 days.[1] This slow clearance is a key differentiator from other IL-1 inhibitors. For instance, anakinra has a half-life of only 4-6 hours, necessitating daily injections, while rilonacept has a half-life of about one week.[11] The extended half-life of canakinumab is the basis for its convenient dosing schedule of every 4 or 8 weeks, which significantly reduces treatment burden and is a major factor in improving long-term patient adherence, particularly in chronic conditions like CAPS.[1] This pharmacokinetic advantage is a defining element of its clinical utility and competitive positioning.

The highly specific mechanism of canakinumab, targeting only IL-1β, contributes to a predictable safety profile. The primary risk—an increased susceptibility to infections—is a direct, on-target consequence of dampening a key component of the innate immune response.[12] This predictability allows for proactive risk mitigation strategies, such as screening for latent tuberculosis and avoiding the use of live vaccines during treatment, thereby creating a manageable safety framework for clinicians.[13]

III. Regulatory Landscape and Approved Indications

The regulatory history of canakinumab illustrates a strategic, evidence-driven expansion from ultra-rare monogenic diseases to more common inflammatory conditions. This progression, guided by an evolving understanding of the role of IL-1β in various pathologies, has been endorsed by major regulatory bodies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

U.S. Food and Drug Administration (FDA) Approval History

Canakinumab's path to market in the United States began with a focus on diseases with a clear and direct link to IL-1β overproduction.

• June 2009: The FDA granted initial approval for Ilaris® for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare, lifelong autoinflammatory diseases. This approval was granted under the orphan drug pathway, recognizing the high unmet need in this patient population.[9]
• May 2013: The indication was expanded to include active Systemic Juvenile Idiopathic Arthritis (SJIA), a severe form of childhood arthritis with prominent systemic inflammation.[9]
• September 2016: Following the granting of three Breakthrough Therapy Designations, the FDA approved canakinumab for three additional Periodic Fever Syndromes: Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), and Familial Mediterranean Fever (FMF).[9] This marked a significant expansion of its use in hereditary autoinflammatory disorders.
• June 2020: The label was further expanded to include Adult-Onset Still's Disease (AOSD), recognizing it as the adult counterpart to SJIA and part of the same disease continuum.[9]
• August 2023: Canakinumab received approval for the symptomatic treatment of gout flares in a narrowly defined adult population for whom standard therapies are inappropriate. This approval came more than a decade after a 2011 FDA advisory panel voted against its approval for gout, citing an unfavorable risk-benefit profile at the time.[9] The eventual approval was based on additional data clarifying its safety and efficacy in a last-line setting.

European Medicines Agency (EMA) Approved Indications

The EMA's approvals for canakinumab have largely paralleled those of the FDA, with some minor but notable differences in approved populations and disease nomenclature, reflecting distinct regulatory philosophies and healthcare system contexts.[12]

• Periodic Fever Syndromes: Approved for adults, adolescents, and children aged 2 years and older.[22]
• CAPS: The EMA label is more explicit in its inclusion of the most severe phenotype, Neonatal-Onset Multisystem Inflammatory Disease (NOMID), also known as Chronic Infantile Neurological, Cutaneous, Articular Syndrome (CINCA), alongside Muckle-Wells Syndrome (MWS) and severe forms of Familial Cold Autoinflammatory Syndrome (FCAS).[22] This highlights a focus on addressing the highest unmet need in the pediatric population.
• TRAPS, HIDS/MKD, and FMF: Indications are similar to the FDA's. For FMF, the EMA specifies that canakinumab should be given in combination with colchicine, if appropriate.[22]
• Still's Disease: Approved for active Still's disease (AOSD and SJIA) in patients aged 2 years and older who have had an inadequate response to NSAIDs and systemic corticosteroids. It can be used as monotherapy or in combination with methotrexate.[22]
• Gouty Arthritis: Approved for the symptomatic treatment of adult patients with frequent gouty arthritis attacks (defined as at least three attacks in the previous 12 months) for whom standard therapies are contraindicated, not tolerated, or ineffective.[22]

The differences between the FDA and EMA labels, such as the lower age limit for periodic fever syndromes (2 years in the EU vs. 4 years for CAPS in the US) and the more explicit inclusion of NOMID by the EMA, may reflect varying approaches to data extrapolation and risk tolerance in pediatric populations with severe, life-altering diseases.

Table 2: Approved Indications and Dosing Summary (FDA & EMA)

Indication	Patient Population (Age/Weight)	FDA-Approved Dose & Frequency 33	EMA-Approved Dose & Frequency 22	Key Clinical Notes
Cryopyrin-Associated Periodic Syndromes (CAPS)	≥4 years (FDA); ≥2 years & ≥7.5 kg (EMA)	>40 kg: 150 mg q8wk. 15-40 kg: 2 mg/kg q8wk (may increase to 3 mg/kg).	>40 kg: 150 mg q8wk. 7.5-40 kg: 2 mg/kg q8wk (may increase to 4 mg/kg).	Dose escalation is based on inadequate clinical response.
TRAPS, HIDS/MKD, FMF	Adult & Pediatric	>40 kg: 150 mg q4wk (may increase to 300 mg q4wk). ≤40 kg: 2 mg/kg q4wk (may increase to 4 mg/kg q4wk).	>40 kg: 150 mg q4wk (may increase to 300 mg q4wk). ≤40 kg: 2 mg/kg q4wk (may increase to 4 mg/kg q4wk).	For FMF, EMA specifies use with colchicine if appropriate.
Still's Disease (SJIA/AOSD)	≥2 years & ≥7.5 kg	4 mg/kg (max 300 mg) q4wk.	4 mg/kg (max 300 mg) q4wk.	Indicated for patients with inadequate response to NSAIDs and corticosteroids.
Gout Flares / Gouty Arthritis	Adults	150 mg as a single dose for a flare. Retreatment ≥12 weeks later.	150 mg as a single dose for a flare. For patients with frequent attacks.	Reserved for patients in whom standard therapies are contraindicated, not tolerated, or ineffective.

IV. Clinical Efficacy and Pivotal Trial Data

The clinical development program for canakinumab has robustly established its efficacy across a spectrum of IL-1β-driven inflammatory diseases. The evidence base is built on a series of well-designed, pivotal clinical trials that led to its regulatory approvals.

Autoinflammatory Periodic Fever Syndromes

Canakinumab has demonstrated profound and sustained efficacy in controlling the signs and symptoms of hereditary periodic fever syndromes.

• Cryopyrin-Associated Periodic Syndromes (CAPS): The efficacy in CAPS is dramatic, reflecting the direct role of IL-1β in this disease's pathogenesis. Data from a pivotal, 24-week, placebo-controlled withdrawal study showed that among patients who initially responded to canakinumab, 0% experienced a disease relapse while continuing treatment, compared to 81% of patients who were switched to placebo.[22] In other supportive studies, 85% of patients treated with canakinumab remained completely free of relapses.[22] This high level of efficacy is observed across all CAPS phenotypes, including FCAS, MWS, and the more severe NOMID, leading to rapid normalization of inflammatory markers and significant improvements in quality of life.[1]
• TRAPS, HIDS/MKD, and FMF: The approval for these conditions was based on the results of the CLUSTER trial, a pivotal Phase III umbrella study involving 181 patients.[22] This trial demonstrated the superiority of canakinumab over placebo in achieving a complete response, defined as resolution of the index flare by day 15 and no new flares over a 16-week period. The response rates were significantly higher in the canakinumab arm across all three cohorts:
• TRAPS: 46% with canakinumab vs. 8% with placebo.[22]
• HIDS/MKD: 35% with canakinumab vs. 6% with placebo.[22]
• FMF (colchicine-resistant): 61% with canakinumab vs. 6% with placebo.[22]

The magnitude of these treatment effects, while substantial, varies across the syndromes. The near-complete response seen in CAPS contrasts with the more modest, though still highly significant, response rates in TRAPS and HIDS/MKD. This likely reflects the underlying pathophysiology; while IL-1β is a critical mediator in all these diseases, its role in TRAPS and HIDS/MKD may be part of a more complex inflammatory network compared to the direct IL-1β overproduction in CAPS. This suggests that some patients with these conditions may have residual disease activity driven by other pathways, potentially requiring alternative or combination therapies.

Still's Disease (SJIA and AOSD)

Canakinumab is a key therapeutic option for Still's disease, a condition characterized by both systemic inflammation and arthritis.

• Systemic Juvenile Idiopathic Arthritis (SJIA): The efficacy in SJIA was established in two pivotal Phase III trials involving patients aged 2 to 19.[32] One trial demonstrated a rapid onset of action, with 84% of patients treated with a single dose of canakinumab achieving an adapted pediatric American College of Rheumatology 30 (ACR30) response by day 15, compared to only 10% of patients receiving placebo.[22] A second trial, which evaluated the maintenance of response, showed that canakinumab reduced the relative risk of a disease flare by 64% compared to placebo.[32] Furthermore, treatment with canakinumab enabled a significant corticosteroid-sparing effect; in one study, nearly half (46%) of patients who were on corticosteroids at baseline were able to discontinue them completely after starting canakinumab.[34]
• Adult-Onset Still's Disease (AOSD): The approval for AOSD was based on the strong evidence in SJIA, the shared pathophysiology between the two conditions, and supportive data from trials in adults.[1] The CONSIDER trial (NCT02204293), a placebo-controlled study in AOSD patients with active arthritis, was terminated early but provided supportive evidence. In the per-protocol analysis, canakinumab-treated patients achieved significantly higher ACR50 (50% vs. 6.7%) and ACR70 (28% vs. 0%) response rates compared to placebo.[36] Real-world evidence from large international registries, such as the AIDA network, has further confirmed that canakinumab is effective in controlling both clinical and laboratory manifestations of Still's disease, regardless of whether it is used as a first-line or subsequent biologic agent.[38]

Refractory Gout Flares

For patients with frequent and severe gout flares who cannot use standard anti-inflammatory treatments, canakinumab offers a potent and targeted alternative. Its efficacy was demonstrated in two randomized, active-controlled, 12-week trials (β-RELIEVED and β-RELIEVED-II) that compared a single 150 mg subcutaneous dose of canakinumab against a 40 mg intramuscular injection of the corticosteroid triamcinolone acetonide (TA).[40]

• Pain Relief: Canakinumab provided superior and rapid pain relief. The mean pain score on a 100 mm visual analogue scale (VAS) at 72 hours was significantly lower in the canakinumab group (25.0 mm) compared to the TA group (35.7 mm).[40]
• Prevention of New Flares: Canakinumab also demonstrated a significant prophylactic effect. Over the 24-week study period (including a 12-week extension), canakinumab reduced the risk of experiencing a new gout flare by 56% compared to TA.[40]

This strong evidence of both acute symptom control and flare prevention was instrumental in securing the eventual FDA approval for this specific, difficult-to-treat patient population.[9]

Real-world clinical experience has underscored the importance of individualized dosing to achieve optimal outcomes. A multi-center observational study revealed that while the overall complete response rate in CAPS was 72%, only 53% of patients achieved this on the standard dose.[41] Dose escalation was required more frequently in children (56%) than in adults (22%), and in patients with more severe phenotypes. Notably, clinical centers that employed a "treat-to-target" strategy—actively adjusting the dose based on clinical and biochemical markers to achieve remission—reported significantly higher complete response rates (94%) than those that did not (50%).[41] This highlights that the dosing regimens from pivotal trials should be viewed as a starting point, with clinicians needing to tailor therapy to the individual patient's disease activity to maximize the therapeutic benefit.

V. The CANTOS Trial: A Paradigm Shift in Cardiovascular Medicine

The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) was a landmark, large-scale clinical trial that fundamentally altered the understanding of atherosclerosis, moving beyond a lipid-centric model to validate inflammation as a direct, modifiable therapeutic target.

Trial Design and Rationale

CANTOS was a randomized, double-blind, placebo-controlled, event-driven trial designed to directly test the inflammatory hypothesis of atherosclerosis.[10] The study enrolled 10,061 patients who had a history of myocardial infarction (MI) and who, despite receiving optimal standard-of-care therapy (including high-intensity statins), had evidence of persistent residual inflammatory risk, defined as a high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or greater.[43] Participants were randomized to receive subcutaneous injections of placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) every three months. The trial's design was critical: by targeting the IL-1β to IL-6 pathway of innate immunity, it could assess the impact of reducing inflammation without affecting LDL cholesterol or other lipid levels, thus isolating the effect of the inflammatory pathway.[10]

Efficacy Endpoints and Key Findings

Patients were followed for a median of 3.7 years.[10]

• Primary Endpoint (MACE): The 150 mg dose of canakinumab met the primary efficacy endpoint, significantly reducing the rate of major adverse cardiovascular events (MACE), a composite of non-fatal MI, non-fatal stroke, or cardiovascular death, by 15% compared to placebo (Hazard Ratio 0.85, 95% Confidence Interval [CI] 0.74–0.98; p=0.021).[42] The 300 mg dose showed a similar, though not statistically significant after multiplicity adjustment, reduction (HR 0.86; p=0.031), while the 50 mg dose was ineffective (HR 0.93; p=0.30).[42]
• Secondary Endpoint (MACE+): The 150 mg and 300 mg doses also significantly reduced the secondary composite endpoint, which included MACE plus hospitalization for unstable angina requiring urgent revascularization, by 17%.[23]
• Biomarker-Guided Efficacy: A crucial, pre-specified analysis revealed that the clinical benefit of canakinumab was almost entirely driven by the degree of inflammatory response. Patients who achieved an on-treatment hsCRP level below 2 mg/L (termed "responders") experienced a highly significant 25% reduction in MACE (p<0.0001) and a 31% reduction in both cardiovascular mortality and all-cause mortality (p<0.001 for both). In stark contrast, patients whose hsCRP remained at or above 2 mg/L ("non-responders") derived no significant clinical benefit.[10] This finding was a powerful demonstration of a personalized medicine approach, indicating that successful hsCRP reduction is a prerequisite for cardiovascular benefit. It effectively transformed the therapeutic question from whether to treat all patients with residual inflammation to a more nuanced strategy: treat, re-measure hsCRP, and only continue therapy in those who demonstrate a robust biological response.

Unexpected Oncology Findings

One of the most striking results from CANTOS was an unexpected and profound effect on cancer mortality. In exploratory analyses, canakinumab treatment was associated with a significant, dose-dependent reduction in the incidence of lung cancer and, most notably, in lung cancer mortality.[12] Patients receiving the 300 mg dose had a

77% reduction in death from lung cancer compared to placebo (HR 0.23, 95% CI 0.10–0.54; p=0.0002).[23] This observation provided the first major clinical evidence in humans that targeting the IL-1β pathway could be a viable strategy in cancer prevention or treatment, likely by altering the pro-tumor inflammatory microenvironment. This serendipitous finding has since launched a new wave of research into the role of IL-1 blockade in immuno-oncology.

Safety Findings

The primary safety concern identified in CANTOS was a small but statistically significant increase in the risk of fatal infection or sepsis. The incidence rate was 0.31 events per 100 person-years in the combined canakinumab groups versus 0.18 in the placebo group (p=0.02).[12] This finding, while concerning, was an anticipated on-target effect of suppressing a key component of the innate immune system. There was no increase in overall mortality, as the reduction in cardiovascular and cancer deaths offset the increase in infection-related deaths.[10]

Table 3: Summary of Pivotal Clinical Trial Efficacy Outcomes

Indication	Trial / Study	Patient Population	Primary Endpoint	Key Result (Canakinumab vs. Control)
CAPS	Lachmann et al., 2009 22	220 adults & children	Proportion of patients with relapse at 24 weeks	0% vs. 81% (Placebo)
TRAPS, HIDS/MKD, FMF	CLUSTER 22	181 adult & pediatric patients	Complete response at Week 16	TRAPS: 46% vs. 8% (Placebo) HIDS/MKD: 35% vs. 6% (Placebo) FMF: 61% vs. 6% (Placebo)
SJIA	Ruperto et al., 2012 22	84 pediatric patients	Adapted pediatric ACR30 response at Day 15	84% vs. 10% (Placebo)
Gout Flares	β-RELIEVED I/II 40	454 adults	Mean pain score (VAS) at 72 hours	25.0 mm vs. 35.7 mm (Triamcinolone)
Atherosclerosis	CANTOS 10	10,061 post-MI patients with hsCRP ≥2 mg/L	MACE (CV death, non-fatal MI, non-fatal stroke)	15% relative risk reduction vs. Placebo (HR 0.85)

VI. Safety, Tolerability, and Risk Management

The safety profile of canakinumab is well-characterized and is primarily dictated by its mechanism of action as a potent inhibitor of IL-1β, a cytokine integral to host defense against pathogens.

Overall Safety Profile and Common Adverse Reactions

Canakinumab is generally well-tolerated in its approved patient populations. However, its immunosuppressive nature leads to a predictable increase in the risk of infections.[12] The most frequently reported adverse drug reactions (defined as >10% in at least one patient population) include infections of the upper respiratory tract (nasopharyngitis, rhinitis, pharyngitis), bronchitis, and gastroenteritis. Other common adverse events include abdominal pain, nausea, diarrhea, headache, vertigo, musculoskeletal pain, and mild-to-moderate injection site reactions.[12]

Serious Adverse Reactions and Risk Management

The prescribing information for canakinumab contains important warnings and precautions that guide its safe use.

• Serious Infections: The most significant risk associated with canakinumab therapy is an increased incidence of serious infections.[21] Physicians must exercise caution when administering the drug to patients with active infections, a history of recurring infections, or underlying conditions that may predispose them to infection (e.g., diabetes). Treatment with canakinumab should not be initiated during an active infection requiring medical intervention, and it should be discontinued if a patient develops a serious infection. While most infections are of the upper respiratory tract and respond to standard therapy, isolated cases of opportunistic infections (e.g., aspergillosis, atypical mycobacterial infections, cytomegalovirus) have been reported.[14]
• Tuberculosis (TB) Screening: Due to the role of IL-1 in granuloma formation and control of mycobacterial infections, all patients must be evaluated for both active and latent tuberculosis infection prior to initiating therapy. Patients testing positive for latent TB should be treated with standard medical practice before canakinumab therapy is started.[27]
• Immunosuppression and Malignancy: As with other immunosuppressants, treatment with canakinumab may increase the risk of malignancies.[12] This theoretical risk is balanced by the unexpected findings from the CANTOS trial, which demonstrated a significant reduction in lung cancer incidence and mortality, suggesting a complex role for IL-1β in tumor biology.[12]
• Macrophage Activation Syndrome (MAS): MAS is a severe, life-threatening complication of systemic inflammatory conditions, particularly Still's disease. It is characterized by uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to a cytokine storm. While clinical trial data do not suggest that canakinumab increases the incidence of MAS, clinicians must remain vigilant for its signs and symptoms (e.g., persistent fever, cytopenias, hepatosplenomegaly, hyperferritinemia), as a flare of the underlying disease can be a trigger.[12]
• Neutropenia and Leukopenia: Transient neutropenia and leukopenia have been observed in patients treated with IL-1 inhibitors. It is recommended that white blood cell (WBC) counts, including neutrophil counts, be assessed prior to initiating treatment, again after 1 to 2 months, and periodically thereafter during chronic therapy.[31]
• Hypersensitivity Reactions: Serious hypersensitivity reactions are a potential risk. Canakinumab is contraindicated in patients with a known history of hypersensitivity to the active substance or any of its excipients.[27]

Drug Interactions and Vaccinations

• Concomitant Immunosuppressants: Co-administration of canakinumab with TNF inhibitors is not recommended, as this combination has been associated with a significantly increased risk of serious infections.[21] Similarly, concurrent use with other IL-1 blockers (anakinra, rilonacept) should be avoided.[27]
• Vaccinations: Live vaccines should not be given concurrently with canakinumab therapy due to the potential for a blunted immune response and risk of infection from the vaccine strain. It is recommended that patients receive all age-appropriate vaccinations according to current immunization guidelines prior to initiating treatment with canakinumab.[6]

VII. Investigational and Off-Label Applications

Beyond its approved indications, the potent anti-inflammatory effects of canakinumab have made it a subject of investigation for a wide range of other diseases and a valuable option for off-label use in refractory cases.

Investigational Pipeline and Discontinued Trials

Canakinumab's development history includes exploration in several major diseases, with varying outcomes.

• Rheumatoid Arthritis (RA): Novartis initially developed canakinumab for RA, but despite showing some efficacy, the program was discontinued after the completion of Phase 2 trials in 2009. The competitive landscape and risk-benefit profile likely did not support further development for this indication.[12]
• Type 1 Diabetes: A Phase 2 trial (NCT00947427) investigated whether canakinumab could preserve beta-cell function in newly diagnosed patients. While the trial was completed, the results did not lead to an approved indication, and a systematic review concluded that canakinumab had negative results in this setting.[49]
• Myelofibrosis: A Phase 2 clinical trial (NCT05467800) is actively recruiting patients with myelofibrosis. This investigation is based on the rationale that chronic inflammation driven by the NLRP3 inflammasome and IL-1β contributes to the pathogenesis of myeloproliferative neoplasms, and that targeting this pathway may improve symptoms and disease outcomes.[51]
• Other Conditions: Canakinumab has also been studied in chronic obstructive pulmonary disease (COPD) and schizophrenia, though these have not resulted in approvals.[12] A biosimilar version of canakinumab, GNR-086, is currently in a Phase 3 trial for AOSD, signaling the future entry of generic competition.[52]

Off-Label Use in Pediatric Autoinflammatory Diseases

In pediatric rheumatology, where conducting large-scale randomized trials can be challenging, off-label use of approved biologics is common for rare and severe diseases that have failed standard therapy. Canakinumab has been used in this capacity for numerous conditions, with case reports and small series providing valuable real-world evidence.[53]

• Monogenic Autoinflammatory Diseases: Canakinumab has shown promise in several monogenic disorders beyond its approved indications. Successful outcomes have been reported in patients with Majeed Syndrome, Blau Syndrome (pediatric granulomatous arthritis), and some cases of Deficiency of IL-1 Receptor Antagonist (DIRA), although results in DIRA have been inconsistent.[53]
• Polygenic and Complex Diseases: Off-label use has extended to more complex, polygenic diseases. Encouraging responses have been observed in refractory cases of pediatric Behçet's Syndrome, particularly for severe uveitis, and in some patients with idiopathic recurrent pericarditis.[53]
• Conditions with Limited or Ineffective Response: The evidence is not universally positive. Canakinumab was reported to be ineffective in a case of PFAPA syndrome and a case of Castleman Disease. Furthermore, a Phase 2a trial in Sickle Cell Anemia did not meet its primary endpoint of pain reduction, although it did show a reduction in inflammatory markers and disease-related flares, suggesting some biological activity.[53]

The pattern of off-label use is not arbitrary but follows a path of scientific rationale. Clinicians have applied canakinumab to diseases that share key pathogenic features with its approved indications, effectively using the drug to probe the role of IL-1β in these conditions. Each successful case report serves as a real-world validation of the underlying hypothesis, often paving the way for more formal clinical investigations and expanding the collective understanding of the spectrum of IL-1β-driven diseases.

VIII. Comparative and Economic Analysis

Canakinumab's position in the therapeutic landscape is defined not only by its clinical efficacy but also by its comparison to alternative treatments and its significant cost.

Therapeutic Positioning vs. Other IL-1 Inhibitors

Three IL-1 inhibitors are approved for clinical use: canakinumab, anakinra, and rilonacept. While all target the IL-1 pathway, they have distinct molecular structures and pharmacokinetic profiles that influence their clinical application.

• Anakinra (Kineret®): A recombinant form of the human IL-1 receptor antagonist (IL-1Ra), anakinra competitively blocks the IL-1RI receptor from binding both IL-1α and IL-1β. Its key feature is a very short half-life of 4-6 hours, which necessitates daily subcutaneous injections. This high dosing frequency can be a significant burden and is associated with a high rate of injection site reactions (ISRs), a common reason for treatment discontinuation.[25] However, the short half-life can be advantageous in situations requiring rapid cessation of immunosuppression, such as in the event of a serious infection.[57]
• Rilonacept (Arcalyst®): A dimeric fusion protein consisting of the ligand-binding domains of the IL-1RI and IL-1RAcP linked to the Fc portion of human IgG1. It acts as a soluble "decoy receptor" or "trap" that binds and neutralizes both IL-1α and IL-1β. It has an intermediate half-life of approximately one week, allowing for weekly injections.[27]

Canakinumab's primary advantages over these agents are its long half-life (~26 days), which allows for dosing every 4 to 8 weeks, and a significantly lower incidence of ISRs. This profile enhances patient convenience and adherence, making it a preferred option for long-term management of chronic diseases.[56] In a comparative observational study in Muckle-Wells Syndrome (MWS), canakinumab was associated with a higher rate of persistent disease remission (93%) compared to anakinra (75%).[50] A real-world study in FMF patients found that canakinumab had a more favorable long-term safety profile, with no severe adverse events leading to discontinuation, whereas several patients on anakinra discontinued due to severe side effects, including anaphylaxis and neutropenia.[25]

Table 4: Comparative Profile of IL-1 Inhibitors

Feature	Canakinumab (Ilaris®)	Anakinra (Kineret®)	Rilonacept (Arcalyst®)
Molecular Target	IL-1β 1	IL-1 Receptor (blocks IL-1α & β) 59	IL-1α & IL-1β (trap) 58
Half-Life	~26 days 1	4–6 hours 11	~7 days 11
Dosing Frequency	Every 4–8 weeks 8	Daily 25	Weekly 58
Approved for CAPS	Yes 2	Yes (NOMID in US; all in EU) 60	Yes 60
Injection Site Reactions	Low incidence 56	High incidence, common reason for discontinuation 25	Frequent 58
Key Clinical Advantage	Long-term convenience and adherence 56	Rapid on/off effect, useful in acute settings 57	Intermediate option between daily and monthly dosing

Health Economic Evaluation

The high acquisition cost of canakinumab is a major factor limiting its use, particularly for indications outside of rare diseases.

• Cardiovascular Risk Reduction: Following the CANTOS trial, multiple health economic analyses concluded that canakinumab is not cost-effective for the secondary prevention of cardiovascular events at its current price.
• A U.S.-based analysis estimated an incremental cost-effectiveness ratio (ICER) of $6.4 million per quality-adjusted life-year (QALY) gained. To meet a conventional willingness-to-pay threshold of $100,000 per QALY, the drug's price would need to be reduced by over 98% (to less than $1150 per year).[16]
• A similar analysis from the Canadian healthcare perspective found an ICER of $535,365 per QALY, concluding that a 91% price reduction would be required for it to be considered cost-effective.[18]
• Rare Diseases: Formal cost-effectiveness studies for canakinumab in its orphan indications like CAPS and other periodic fever syndromes are limited. However, the high price is generally considered more justifiable in this context due to the severity of the diseases, the profound clinical benefit (often life-transforming), the small patient populations, and the lack of effective alternative treatments.[62] The value proposition is therefore substantially different and more favorable in the rare disease setting.

The economic analysis of the CANTOS trial serves as a critical case study in the challenges of pharmaceutical pricing. The failure of canakinumab to be adopted for cardiovascular disease was not due to a lack of clinical efficacy, but rather a failure of a pricing model that could not adapt to different value propositions across vastly different diseases. The price, set based on its high value in a small population with a rare disease, was untenable when applied to a very large population with a common disease where the absolute benefit is more modest and effective, inexpensive therapies already exist. This highlights a structural challenge for the pharmaceutical industry and public health systems: how to implement indication-specific pricing to ensure that innovative medicines can be accessed by all patient populations who stand to benefit.

IX. Conclusion and Future Perspectives

Canakinumab has established itself as a cornerstone therapeutic agent in the management of a specific subset of inflammatory diseases. Its journey from a targeted therapy for ultra-rare genetic syndromes to a proof-of-concept molecule in one of the most common chronic diseases of mankind is a testament to the power of translational medicine. It is a highly effective and specific IL-1β inhibitor that has revolutionized the treatment of CAPS, TRAPS, HIDS/MKD, FMF, and Still's disease, offering sustained disease control and a manageable safety profile. Its favorable long-acting pharmacokinetic profile provides a distinct clinical advantage over other IL-1 inhibitors, enhancing patient adherence and quality of life.

The impact of canakinumab extends far beyond its approved indications. The CANTOS trial was a watershed moment, providing definitive validation of the inflammatory hypothesis of atherosclerosis and fundamentally changing the direction of cardiovascular research. The unexpected findings related to lung cancer have similarly opened a new and promising frontier in immuno-oncology, demonstrating how large-scale clinical trials can yield transformative insights that cross therapeutic areas.

The future of canakinumab and the field of anti-inflammatory therapy it has helped to shape will likely be defined by several key trends:

• Biosimilar Competition: The development of canakinumab biosimilars is already underway.[52] The eventual market entry of these agents will increase competition, which is expected to drive down costs and improve patient access. This could potentially alter the economic calculus for its use, though it is unlikely to become a first-line agent for cardiovascular disease without drastic price reductions.
• Expansion to New Indications: Research continues to explore the role of IL-1β in other diseases. Ongoing trials in conditions like myelofibrosis may yet expand canakinumab's therapeutic reach, particularly in diseases where inflammation is a key component of the pathology.[51]
• The Rise of Personalized, Biomarker-Guided Therapy: Perhaps the most enduring legacy of the canakinumab story, particularly from the CANTOS trial, is the validation of a biomarker-driven approach. The finding that clinical benefit was restricted to patients who achieved a significant on-treatment reduction in hsCRP is a powerful lesson.[10] Future development and clinical use of potent anti-inflammatory agents will increasingly rely on identifying the right patient through baseline biomarkers and confirming therapeutic response to justify the cost and risk of long-term treatment.

In conclusion, canakinumab is more than just a successful drug; it is a molecule that has both transformed patients' lives and advanced fundamental scientific understanding. Its story encapsulates the triumphs of targeted drug design, the complexities of clinical development, the challenges of modern healthcare economics, and the exciting future of personalized anti-inflammatory medicine.

Works cited

1. Canakinumab: Uses, Interactions, Mechanism of Action | DrugBank ..., accessed July 21, 2025, https://go.drugbank.com/drugs/DB06168
2. Ilaris (Canakinumab Injection): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed July 21, 2025, https://www.rxlist.com/ilaris-drug.htm
3. Canakinumab - PMC - PubMed Central, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2828573/
4. canakinumab - E-lactancia, accessed July 21, 2025, https://e-lactancia.org/media/papers/Canakinumab-DS-Novartis_2021.pdf
5. go.drugbank.com, accessed July 21, 2025, https://go.drugbank.com/drugs/DB06168#:~:text=Canakinumab%20is%20marketed%20under%20the,of%20age%20and%20older%20to
6. Canakinumab (subcutaneous route) - Side effects & uses - Mayo Clinic, accessed July 21, 2025, https://www.mayoclinic.org/drugs-supplements/canakinumab-subcutaneous-route/description/drg-20073102
7. Ilaris (Canakinumab) Injection: Uses & Side Effects - Cleveland Clinic, accessed July 21, 2025, https://my.clevelandclinic.org/health/drugs/20297-canakinumab-injection
8. Ilaris (canakinumab) dosing, indications, interactions, adverse effects, and more, accessed July 21, 2025, https://reference.medscape.com/drug/ilaris-canakinumab-999214
9. Ilaris (canakinumab) FDA Approval History - Drugs.com, accessed July 21, 2025, https://www.drugs.com/history/ilaris.html
10. Antiinflammatory Therapy in Clinical Care: The CANTOS Trial and Beyond - Frontiers, accessed July 21, 2025, https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2018.00062/full
11. Pharmacokinetic and Pharmacodynamic Properties of ..., accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3584253/
12. Canakinumab - Wikipedia, accessed July 21, 2025, https://en.wikipedia.org/wiki/Canakinumab
13. Canakinumab (Ilaris) - American College of Rheumatology, accessed July 21, 2025, https://rheumatology.org/patients/canakinumab-ilaris
14. Canakinumab (Ilaris®) RMP Summary - Swissmedic, accessed July 21, 2025, https://www.swissmedic.ch/dam/swissmedic/de/dokumente/marktueberwachung/rmp/canakinumab_ilaris_rmp-summary.pdf.download.pdf/Canakinumab_Ilaris_EU_RMP_Summary_v1.0.pdf
15. FDA Approves Canakinumab to Treat Gout Flares - The Rheumatologist, accessed July 21, 2025, https://www.the-rheumatologist.org/article/fda-approves-canakinumab-to-treat-gout-flares/
16. pubmed.ncbi.nlm.nih.gov, accessed July 21, 2025, https://pubmed.ncbi.nlm.nih.gov/30649147/#:~:text=Results%3A%20Adding%20canakinumab%20to%20standard,%246.4%20million%20per%20QALY%20gained.
17. Cost-effectiveness of Canakinumab for Prevention of Recurrent Cardiovascular Events - PubMed, accessed July 21, 2025, https://pubmed.ncbi.nlm.nih.gov/30649147/
18. Cost-Effectiveness of Canakinumab From a Canadian Perspective for Recurrent Cardiovascular Events - PMC, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9123368/
19. Canakinumab Injection: MedlinePlus Drug Information, accessed July 21, 2025, https://medlineplus.gov/druginfo/meds/a622024.html
20. What is the mechanism of action of Canakinumab? - Patsnap Synapse, accessed July 21, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-action-of-canakinumab
21. ILARIS® (canakinumab) for injection, for ... - accessdata.fda.gov, accessed July 21, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/BLA125319_858687lbl.pdf
22. Ilaris | European Medicines Agency (EMA), accessed July 21, 2025, https://www.ema.europa.eu/en/medicines/human/EPAR/ilaris
23. CANTOS results show that inhibiting inflammation reduces CV events and possibly lung cancer rates - - PACE-CME, accessed July 21, 2025, https://pace-cme.org/news/2454922/
24. The Pharmacology of IL-1 Inhibitors: A Deep Dive, accessed July 21, 2025, https://www.numberanalytics.com/blog/pharmacology-il-1-inhibitors-deep-dive
25. Long-term safety and efficacy of anakinra and canakinumab in ..., accessed July 21, 2025, https://www.researchgate.net/publication/353221936_Long-term_safety_and_efficacy_of_anakinra_and_canakinumab_in_patients_with_familial_Mediterranean_fever_a_single-centre_real-life_study_with_101_patients
26. Reasons for canakinumab initiation among patients with periodic fever syndromes: a retrospective medical chart review from the United States - PMC, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8439059/
27. Autoinflammatory Disease Treatment | ILARIS® (canakinumab), accessed July 21, 2025, https://www.ilaris.com/
28. Novartis receives three FDA Breakthrough Therapy Designations for Ilaris to treat rare types of Periodic Fever Syndromes, accessed July 21, 2025, https://www.novartis.com/us-en/news/media-releases/novartis-receives-three-fda-breakthrough-therapy-designations-ilaris-treat-rare-types-periodic-fever-syndromes
29. Novartis receives three FDA Breakthrough Therapy Designations for Ilaris to treat rare types of Periodic Fever Syndromes, accessed July 21, 2025, https://novartis.gcs-web.com/novartis-receives-three-fda-breakthrough-therapy-designations-for-canakinumab
30. Novartis receives positive CHMP recommendation for Ilaris® to treat rare diseases in adults and children called Periodic Fever Syndromes, accessed July 21, 2025, https://www.novartis.com/news/media-releases/novartis-receives-positive-chmp-recommendation-ilaris-treat-rare-diseases-adults-and-children-called-periodic-fever-syndromes
31. TRANSPARENCY COMMITTEE, accessed July 21, 2025, https://www.has-sante.fr/jcms/c_1765463/fr/ilaris-version-anglaise-ct13360
32. European Commission Approves Canakinumab in SJIA - Medscape, accessed July 21, 2025, https://www.medscape.com/viewarticle/810353
33. ILARIS® (canakinumab) - This label may not be the latest approved ..., accessed July 21, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125319s107lbl.pdf
34. Treatment Results | AOSD | ILARIS® (canakinumab), accessed July 21, 2025, https://www.ilaris.com/aosd/aosd-results
35. Development and Role in Therapy of Canakinumab in Adult-Onset Still's Disease - PMC, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6160871/
36. Canakinumab for Treatment of Adult-Onset Still's Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial - PMC - PubMed Central, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7392486/
37. Canakinumab for Treatment of Adult-Onset Still's Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial, accessed July 21, 2025, https://ard.bmj.com/content/79/8/1090
38. Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease - Frontiers, accessed July 21, 2025, https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1256243/full
39. (PDF) Efficacy of canakinumab in patients with Still's disease across different lines of biologic therapy: real-life data from the International AIDA Network Registry for Still's Disease - ResearchGate, accessed July 21, 2025, https://www.researchgate.net/publication/376468602_Efficacy_of_canakinumab_in_patients_with_Still's_disease_across_different_lines_of_biologic_therapy_real-life_data_from_the_International_AIDA_Network_Registry_for_Still's_Disease
40. Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions - PubMed, accessed July 21, 2025, https://pubmed.ncbi.nlm.nih.gov/22586173/
41. Real-life effectiveness of canakinumab in cryopyrin-associated periodic syndrome | Rheumatology | Oxford Academic, accessed July 21, 2025, https://academic.oup.com/rheumatology/article/55/4/689/1833374
42. CANTOS Study Shows Reducing Inflammation Cuts Cardiovascular Disease, Lung Cancer Risk | DAIC - Diagnostic and Interventional Cardiology, accessed July 21, 2025, https://www.dicardiology.com/content/cantos-study-shows-reducing-inflammation-cuts-cardiovascular-disease-lung-cancer-risk
43. Canakinumab Effects on Erythropoiesis, Cardiovascular Risk, and Clonal Hematopoiesis: Proteogenomic Analysis of the Cantos Randomized Clinical Trial | Blood | American Society of Hematology, accessed July 21, 2025, https://ashpublications.org/blood/article/140/Supplement%201/2236/491924/Canakinumab-Effects-on-Erythropoiesis
44. Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade | JACC: Advances, accessed July 21, 2025, https://www.jacc.org/doi/10.1016/j.jacadv.2024.101583
45. Canakinumab Anti-Inflammatory Thrombosis Outcomes Study ..., accessed July 21, 2025, https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2017/08/26/08/35/CANTOS
46. Ilaris, INN-canakinumab, accessed July 21, 2025, https://ec.europa.eu/health/documents/community-register/2017/20170322137164/anx_137164_en.pdf
47. What the Experts Are Saying | Still's Disease | ILARIS® (canakinumab) | HCP, accessed July 21, 2025, https://www.ilarishcp.com/stills-disease/hear-from-an-expert/
48. Canakinumab Completed Phase 2 Trials for Rheumatoid Arthritis Treatment - DrugBank, accessed July 21, 2025, https://go.drugbank.com/drugs/DB06168/clinical_trials?conditions=DBCOND0027961&phase=2&purpose=treatment&status=completed
49. Type One Diabetes Completed Phase 2 Trials for Canakinumab (DB06168) - DrugBank, accessed July 21, 2025, https://go.drugbank.com/indications/DBCOND0076728/clinical_trials/DB06168?phase=2&status=completed
50. Systematic Review of Safety and Efficacy of IL-1-Targeted Biologics ..., accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9296857/
51. Canakinumab Recruiting Phase 2 Trials for Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) / PV-MF / Primary Myelofibrosis (PMF) / ET-MF / Post Polycythemia Vera Myelofibrosis Treatment - DrugBank, accessed July 21, 2025, https://go.drugbank.com/drugs/DB06168/clinical_trials?conditions=DBCOND0150201%2CDBCOND0062303%2CDBCOND0069581%2CDBCOND0044387%2CDBCOND0150203&phase=2&purpose=treatment&status=recruiting
52. Adult-Onset Still´s Disease Recruiting Phase 3 Trials for Canakinumab (DB06168), accessed July 21, 2025, https://go.drugbank.com/indications/DBCOND0071378/clinical_trials/DB06168?phase=3&status=recruiting
53. Off-label use of canakinumab in pediatric rheumatology and rare ..., accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9622922/
54. Off-label use of canakinumab in pediatric rheumatology and rare diseases - PubMed, accessed July 21, 2025, https://pubmed.ncbi.nlm.nih.gov/36330067/
55. Off-label use of anti-IL-1 drugs in rheumatic diseases - ResearchGate, accessed July 21, 2025, https://www.researchgate.net/publication/350919207_Off-label_use_of_anti-IL-1_drugs_in_rheumatic_diseases
56. Critical appraisal of canakinumab in the treatment of adults and children with cryopyrin-associated periodic syndrome (CAPS) - PubMed Central, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC2880341/
57. The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease - PubMed Central, accessed July 21, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC8999740/
58. Review IL-1 inhibition in familial Mediterranean fever: clinical ..., accessed July 21, 2025, https://www.clinexprheumatol.org/article.asp?a=19011
59. Efficacy and safety of anakinra and canakinumab in PSTPIP1-associated inflammatory diseases: a comprehensive scoping review - Frontiers, accessed July 21, 2025, https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1339337/full
60. Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome | RMD Open, accessed July 21, 2025, https://rmdopen.bmj.com/content/6/2/e001227
61. Cost-effectiveness of Canakinumab for Prevention of Recurrent Cardiovascular Events | Request PDF - ResearchGate, accessed July 21, 2025, https://www.researchgate.net/publication/330433738_Cost-effectiveness_of_Canakinumab_for_Prevention_of_Recurrent_Cardiovascular_Events
62. Canakinumab for Atherosclerotic Cardiovascular Disease: Effectiveness and Value - ICER, accessed July 21, 2025, https://icer.org/wp-content/uploads/2020/10/ICER_ASCVD_Revised_Scope_083018.pdf
63. Institute for Clinical and Economic Review to Assess Canakinumab for Atherosclerosis, accessed July 21, 2025, https://icer.org/news-insights/press-releases/atherosclerosis-topic/