Ixekizumab (Taltz®): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Safety Profile

Section 1: Introduction and Drug Profile

1.1. Overview and Therapeutic Classification

Ixekizumab is a high-affinity, humanized monoclonal antibody that represents a significant advancement in the targeted treatment of several chronic, immune-mediated inflammatory diseases.[1] Marketed under the brand name Taltz®, it is classified as a biologic therapy, specifically an interleukin inhibitor, that functions by selectively targeting and neutralizing the pro-inflammatory cytokine Interleukin-17A (IL-17A).[3] Its development and application are rooted in the growing understanding of the central role of the T helper 17 (Th17) cell pathway in the pathophysiology of conditions such as moderate-to-severe plaque psoriasis, active psoriatic arthritis, active ankylosing spondylitis, and active non-radiographic axial spondyloarthritis.[1]

The precise classification of Ixekizumab as an "Interleukin-17A Antagonist" is a critical distinction that reflects a strategic evolution in the design of biologic drugs. The IL-17 family of cytokines includes several members (IL-17A, B, C, D, E, and F), each with potentially distinct biological roles.[10] Early research identified the IL-17A isoform as the primary pathogenic driver in the targeted inflammatory conditions.[1] Consequently, Ixekizumab was engineered with high specificity to bind and neutralize only IL-17A, including its homodimeric (IL-17A/A) and heterodimeric (IL-17A/F) forms, without interacting with other family members.[10] This targeted approach contrasts with broader immunosuppressive agents, such as conventional disease-modifying antirheumatic drugs (DMARDs) or even first-generation biologics like tumor necrosis factor-alpha (TNF-α) inhibitors, which have a more widespread impact on the immune system. It also differs from other biologics that might target the IL-17 receptor, an action that would block signaling from multiple IL-17 family cytokines.[13] The deliberate design of Ixekizumab to isolate and neutralize the IL-17A-mediated pathway represents a precision-medicine strategy aimed at maximizing therapeutic efficacy while minimizing potential off-target effects that could arise from broader pathway inhibition.

1.2. Drug Identification and Manufacturer

The consistent and accurate identification of a therapeutic agent is paramount in clinical and research settings. Ixekizumab is recognized by a set of unique identifiers that distinguish it across pharmaceutical, chemical, and regulatory domains. These are consolidated in Table 1. The drug was developed and is manufactured by Eli Lilly and Company, a global pharmaceutical firm.[2] During its development phase, it was referred to by the code LY-2439821.[1] Upon its approval, it was designated as a New Molecular Entity (NME), signifying its novel therapeutic action.[14] It does not hold an Orphan Drug Status, which is consistent with its development for indications such as psoriasis and arthritis that affect a substantial patient population.[14]

Identifier	Value
Generic Name	Ixekizumab
Brand Name	Taltz®
DrugBank ID	DB11569
CAS Number	1143503-69-8
Drug Class	Biotech, Monoclonal Antibody, Interleukin-17A Antagonist
Manufacturer	Eli Lilly and Company
Developmental Code	LY-2439821

Section 2: Molecular Biology and Manufacturing

2.1. Chemical Structure and Composition

Ixekizumab is a complex glycoprotein biologic, specifically a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody.[1] The term "humanized" indicates that the antibody's protein sequences, particularly in the constant regions, have been modified to closely resemble human antibodies, a process intended to reduce its immunogenicity in patients.

The fundamental structure of Ixekizumab consists of four polypeptide chains: two identical heavy chains, each comprising 445 amino acids, and two identical light chains, each comprising 219 amino acids.[1] These chains are covalently linked by inter-chain disulfide bridges, forming a characteristic Y-shaped molecule. The total molecular weight of the protein backbone is approximately 146,158 Daltons.[1] The empirical chemical formula for the protein component is

C6492​H10012​N1728​O2028​S46​.[1] As is typical for monoclonal antibodies, Ixekizumab undergoes post-translational modification in the form of glycosylation; both heavy chains are glycosylated at the asparagine residue in position 296.[13]

The molecular engineering of Ixekizumab includes specific modifications designed to optimize its therapeutic function and stability. The choice of the IgG4 subclass is itself a deliberate design feature. Among the human IgG subclasses, IgG4 exhibits the weakest effector functions, meaning it has a very low capacity to trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Since the therapeutic goal of Ixekizumab is to neutralize a soluble cytokine (IL-17A) rather than to destroy a target cell, these effector functions are not only unnecessary but also undesirable, as they could lead to off-target cell killing and increased inflammatory responses. The selection of IgG4 thus creates a "quiet" antibody focused purely on neutralization. Furthermore, to enhance the stability of the IgG4 scaffold, which can be prone to a phenomenon known as Fab-arm exchange, a key amino acid substitution was made. A serine residue in the hinge region of the heavy chain was replaced with a proline.[13] This modification is a well-established engineering strategy that prevents the formation of "half-antibodies" and ensures the structural integrity of the bivalent molecule, leading to a more stable and functionally consistent therapeutic product. An additional modification is the removal of the C-terminal lysine residue from the heavy chains, a common practice in monoclonal antibody manufacturing to increase product homogeneity.[13]

2.2. Biotechnological Production and Formulation

Ixekizumab is manufactured using advanced biotechnological processes. It is produced via recombinant DNA technology in a stable, well-characterized mammalian cell line: Chinese Hamster Ovary (CHO) cells.[1] This process involves introducing the genes encoding the humanized heavy and light chains of Ixekizumab into the CHO cells, which then express and secrete the fully assembled antibody into the cell culture medium. Following the culture phase, the antibody is harvested and subjected to a multi-step purification process using standard bioprocessing technologies, such as protein A chromatography, to ensure high purity and remove host cell proteins and other contaminants.[1]

The global manufacturing is divided between specialized sites. The bulk drug substance is produced at an Eli Lilly S.A. facility in County Cork, Ireland.[15] The final formulated drug product is then manufactured, filled into its delivery devices (syringes and autoinjectors), labeled, and packaged at Eli Lilly and Company's facilities in Indianapolis, Indiana, USA.[15]

The final product is formulated as a sterile, preservative-free, clear, and colorless to slightly yellow solution intended for subcutaneous injection.[17] The solution is buffered to a pH of approximately 5.7 (range 5.3 to 6.1).[17] A significant evolution in the drug's formulation was the introduction of a citrate-free version. The original formulation contained citrate as a buffer, which is known to be associated with injection site pain. The newer, citrate-free formulation was developed to improve the patient experience by significantly reducing this pain.[22] A clinical study demonstrated an 86% reduction in injection site pain with the citrate-free formulation compared to the original, without altering the drug's pharmacokinetic profile or efficacy.[23] The excipients in the current formulation include sucrose as a stabilizer, polysorbate 80 as a surfactant to prevent protein aggregation, and water for injection, with sodium hydroxide potentially used for pH adjustment.[21] The manufacturing process for the final formulation involves the careful mixing of these excipients, multiple filtration steps for bioburden reduction, and aseptic filling into the final delivery devices.[21]

Section 3: Mechanism of Action and Pharmacodynamics

3.1. The Role of the IL-17A Pathway in Pathophysiology

To comprehend the mechanism of Ixekizumab, it is essential to first understand the immunological pathway it targets. Interleukin-17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of lymphocytes and is a potent driver of inflammation.[1] In healthy individuals, IL-17A plays a vital role in host defense, particularly at mucosal and epithelial barriers, by orchestrating immune responses against extracellular bacteria and fungi.[12] However, in a range of autoimmune diseases, this pathway becomes dysregulated and overactive, contributing directly to chronic inflammation and tissue damage.[1]

In conditions like plaque psoriasis, psoriatic arthritis, and axial spondyloarthritis, elevated levels of IL-17A are found in affected tissues (skin, synovium) and in the circulation.[1] Biologically active IL-17A exists primarily as a homodimer (composed of two IL-17A subunits) or as a heterodimer with the closely related IL-17F cytokine.[26] It exerts its effects by binding to a receptor complex, composed of the IL-17RA and IL-17RC subunits, which is expressed on a wide variety of cell types, including keratinocytes in the skin, fibroblasts in the joints, and endothelial cells.[16]

The binding of IL-17A to its receptor initiates a downstream signaling cascade, activating pathways such as NF-κB and MAPK.[16] This signaling leads to the production and release of a host of other pro-inflammatory mediators, including other cytokines (e.g., IL-6, TNF-α), chemokines that recruit neutrophils and other immune cells to the site of inflammation, and matrix metalloproteinases that can degrade tissue.[2] In psoriasis, this cascade drives the hyperproliferation and abnormal differentiation of keratinocytes, resulting in the characteristic erythematous, thickened, and scaly plaques.[13] In psoriatic arthritis and axial spondyloarthritis, it promotes synovitis, enthesitis (inflammation where tendons and ligaments attach to bone), bone erosion, and aberrant new bone formation, leading to joint pain, stiffness, and structural damage.[16]

3.2. Molecular Target Binding and Neutralization

Ixekizumab functions as a direct antagonist of the IL-17A cytokine.[1] It is a high-affinity monoclonal antibody engineered to selectively bind to IL-17A and physically prevent it from interacting with its cell surface receptor.[1] The affinity of this binding interaction is exceptionally high, a key determinant of the drug's potency. The dissociation constant (

KD​), a measure of binding affinity where a lower value indicates a tighter bond, has been quantified to be approximately 1.8 picomolar (pM) for the IL-17A homodimer and less than 3 pM for the IL-17A/F heterodimer.[11] This picomolar-level affinity signifies an extremely stable and durable interaction between the antibody and its target.

This molecular property is fundamental to the drug's clinical profile. The rapid association rate (kon) and extremely slow dissociation rate (koff) that characterize such a high-affinity interaction mean that Ixekizumab can efficiently "scavenge" and neutralize IL-17A from the circulation and inflamed tissues, even at low drug concentrations.[16] This rapid and comprehensive shutdown of the IL-17A signaling pathway is the direct molecular basis for the rapid onset of clinical action observed in trials, where significant improvements in psoriasis symptoms can be seen as early as the first week of treatment, and approximately half of patients achieve a 75% improvement in skin lesions by the fourth week.[2]

The specificity of this interaction is equally critical. Preclinical studies have demonstrated that Ixekizumab binds with high affinity to human and cynomolgus monkey IL-17A but does not cross-react with other members of the human IL-17 cytokine family (IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F) or with rodent IL-17A.[10] This high degree of specificity ensures that the therapeutic effect is confined to the IL-17A axis, which is believed to be the primary pathogenic driver, while leaving the functions of other potentially beneficial IL-17 family members intact. By physically occupying the receptor-binding site on the IL-17A cytokine, Ixekizumab acts as a competitive inhibitor, completely blocking the ability of IL-17A to engage the IL-17RA subunit of its receptor complex.[10]

3.3. Downstream Immunological Effects

The neutralization of IL-17A by Ixekizumab leads to a cascade of downstream immunological effects that collectively result in the amelioration of disease. By preventing IL-17A from signaling through its receptor, Ixekizumab effectively halts the production and release of numerous downstream inflammatory mediators.[2] This disruption of the pro-inflammatory feedback loop leads to a marked reduction in tissue inflammation.

In the skin of patients with psoriasis, this translates to a decrease in the activation and hyperproliferation of keratinocytes, a reduction in the infiltration of neutrophils and other immune cells into the epidermis and dermis, and a normalization of skin architecture.[13] Clinically, this manifests as a rapid reduction in the erythema (redness), induration (thickness), and desquamation (scaling) of psoriatic plaques.

In the joints and axial skeleton of patients with psoriatic arthritis and axial spondyloarthritis, the inhibition of IL-17A signaling leads to a reduction in synovial inflammation and enthesitis. This results in clinically meaningful improvements in joint pain, swelling, and tenderness.[6] Furthermore, by modulating the inflammatory environment that drives both bone erosion and pathological bone formation, Ixekizumab helps to inhibit the progression of structural joint damage. Patients report significant reductions in hallmark symptoms such as inflammatory back pain, morning stiffness, and fatigue, leading to improved physical function and overall quality of life.[6]

Section 4: Pharmacokinetic Profile

The pharmacokinetic (PK) profile of Ixekizumab, which describes its absorption, distribution, metabolism, and elimination (ADME), has been well-characterized and is consistent across all its approved adult indications.[34]

4.1. Absorption

Ixekizumab is administered via subcutaneous injection, from which it is absorbed into the systemic circulation.[5] Following a single 160 mg subcutaneous dose in patients with plaque psoriasis, the drug is absorbed relatively slowly, reaching peak mean serum concentrations (

Cmax​) of 16.2 mcg/mL after approximately 4 to 7 days (Tmax​).[1] The absolute bioavailability, which is the fraction of the administered dose that reaches the systemic circulation, is substantial, ranging from 60% to 81% in various analyses.[2] Studies have shown that the site of injection can influence absorption, with administration into the thigh resulting in higher bioavailability compared to injections in the abdomen or arm.[2]

With the recommended dosing regimens, steady-state concentrations are achieved in a predictable manner. Following the induction regimen for plaque psoriasis (160 mg at week 0, then 80 mg every 2 weeks), steady-state is reached by week 8. After switching to the maintenance regimen of 80 mg every 4 weeks at week 12, a new, lower steady-state is achieved approximately 10 weeks later.[2]

4.2. Distribution

Once absorbed, Ixekizumab distributes primarily within the circulatory and interstitial fluid compartments. The mean volume of distribution at steady-state (Vss​) is approximately 7.11 L.[1] This is a relatively small volume of distribution, which is characteristic of large protein molecules like monoclonal antibodies that do not readily penetrate into deep tissue compartments or cross the blood-brain barrier. This distribution profile is well-suited for its therapeutic purpose, as it ensures the drug is concentrated in the vascular and interstitial spaces where it can effectively bind and neutralize the soluble IL-17A cytokine.[16]

4.3. Metabolism and Elimination

The metabolic pathway of Ixekizumab has not been characterized through specific studies, as is common for monoclonal antibodies.[1] As a humanized IgG4 protein, it is not metabolized by the hepatic cytochrome P450 (CYP) enzyme system that is responsible for the clearance of most small-molecule drugs. Instead, Ixekizumab is presumed to be eliminated through general protein catabolism.[1] This process involves being taken up by cells throughout the body and degraded into its constituent small peptides and amino acids, which are then recycled for new protein synthesis. This is the same pathway by which endogenous immunoglobulins are cleared.

The mean systemic clearance of Ixekizumab is approximately 0.39 L/day.[1] The mean elimination half-life is approximately 13 days.[1] This relatively long half-life supports the intermittent dosing schedules of every 2 or 4 weeks.

4.4. Pharmacokinetics in Special Populations and Dose Linearity

Ixekizumab exhibits linear, or dose-proportional, pharmacokinetics over the clinically relevant dose range.[13] This linearity means that changes in dose result in proportional changes in drug exposure (e.g., doubling the dose doubles the serum concentration), which simplifies dosing and makes the drug's behavior predictable.

The pharmacokinetic properties of large protein therapeutics are often influenced by patient body weight. For Ixekizumab, both clearance and volume of distribution have been shown to increase as body weight increases.[2] This relationship provides the scientific rationale for the weight-based dosing strategy employed for the pediatric population, which is designed to achieve drug exposures and mean trough concentrations that are comparable to those proven effective in adults.[19]

In contrast, population pharmacokinetic analyses have shown that age does not have a clinically significant effect on the clearance of Ixekizumab in adult patients, and therefore, no dose adjustments are required for geriatric patients.[13] Because monoclonal antibodies are cleared via catabolism rather than through renal or hepatic pathways, the PK profile is not expected to be significantly altered by renal or hepatic impairment, and specific studies in these populations have not been conducted.[19] This predictable PK profile, which is largely independent of organ function, represents a significant clinical advantage over many small-molecule drugs that often require complex dose adjustments and have extensive drug-drug interaction profiles mediated by metabolic enzymes.

Section 5: Clinical Efficacy in Approved Indications

The clinical development program for Ixekizumab has been extensive, with multiple large-scale, pivotal Phase III trials establishing its efficacy and safety across a spectrum of immune-mediated inflammatory diseases.

5.1. Plaque Psoriasis (Adult and Pediatric)

The foundational evidence for the efficacy of Ixekizumab in adults with moderate-to-severe plaque psoriasis was established in a robust clinical trial program known as UNCOVER, which included three pivotal, multicenter, randomized, double-blind, placebo-controlled trials: UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), and UNCOVER-3 (NCT01646177).[27] These trials enrolled a total of 3,866 patients who were candidates for systemic therapy or phototherapy.[13] The UNCOVER-2 and UNCOVER-3 trials also included an active comparator arm with etanercept, a widely used TNF-α inhibitor.[34]

The co-primary endpoints in these studies, assessed at week 12, were the proportion of patients achieving at least a 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) and the proportion of patients achieving a static Physician's Global Assessment (sPGA) score of 0 (clear) or 1 (minimal).[34] The results, summarized in Table 2, were remarkable and demonstrated profound efficacy.

The performance of Ixekizumab in these trials, particularly its ability to induce complete skin clearance (PASI 100), represented a significant shift in the therapeutic landscape for psoriasis. Historically, PASI 75 was considered the benchmark for a successful clinical outcome in psoriasis trials. The high rates of PASI 100 achieved with Ixekizumab (35-40% at week 12) helped to establish "completely clear skin" as a realistic and achievable treatment goal, fundamentally altering the expectations of both clinicians and patients.[13] This level of efficacy was sustained long-term; data from the UNCOVER-3 open-label extension showed that at 5 years (264 weeks), 67% of patients maintained a PASI 90 response and 46% maintained a PASI 100 response.[39]

Trial	Treatment Arm	sPGA 0/1 (%)	sPGA 0 (%)	PASI 75 (%)	PASI 90 (%)	PASI 100 (%)
UNCOVER-1	Ixekizumab 80 mg Q2W (N=433)	82	37	89	71	35
	Placebo (N=431)	3	0	4	1	0
UNCOVER-2	Ixekizumab 80 mg Q2W (N=351)	83	42	90	71	40
	Placebo (N=168)	2	1	2	1	1
	Etanercept 50 mg BIW (N=358)	39	7	48	23	7
UNCOVER-3	Ixekizumab 80 mg Q2W (N=385)	81	40	87	68	38
	Placebo (N=193)	7	0	7	3	0
	Etanercept 50 mg BIW (N=382)	42	7	53	26	7
Data from week 12 of pivotal trials. sPGA 0/1: static Physician's Global Assessment of clear or minimal. PASI 75/90/100: Psoriasis Area and Severity Index improvement of 75%/90%/100%. Q2W: every 2 weeks. BIW: twice weekly. 32

The efficacy of Ixekizumab was also established in the pediatric population (ages 6 to <18 years) in the IXORA-PEDS trial (NCT03073200).[45] At week 12, 89% of children and adolescents treated with weight-based dosing of Ixekizumab achieved PASI 75, compared to only 25% of those receiving placebo. Similarly, 81% achieved an sPGA score of 0 or 1, versus 11% for placebo, demonstrating robust efficacy in this younger population.[46]

5.2. Psoriatic Arthritis (PsA)

The efficacy of Ixekizumab for the treatment of active psoriatic arthritis was demonstrated in the SPIRIT clinical trial program, which included two pivotal Phase III studies: SPIRIT-P1 (NCT01695239) in biologic-naïve patients and SPIRIT-P2 (NCT02349295) in patients who had previously had an inadequate response or intolerance to TNF inhibitors (TNFi-experienced).[19] The primary endpoint for both studies was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 24.

In the SPIRIT-P1 trial, which included an active reference arm of adalimumab, Ixekizumab was shown to be highly effective in biologic-naïve patients.[31] In the more difficult-to-treat TNFi-experienced population in SPIRIT-P2, Ixekizumab also demonstrated significant superiority over placebo.[19] Beyond improvements in joint symptoms, Ixekizumab also proved effective in treating other domains of PsA, including skin psoriasis, enthesitis, and dactylitis, and critically, it was shown to inhibit the progression of structural joint damage as measured by the modified Total Sharp Score (mTSS).[19] Key results are summarized in Table 3. The improvements in clinical signs and symptoms were sustained for up to 3 years in the long-term extension of the SPIRIT-P1 study.[49]

Trial / Population	Treatment Arm	ACR20 (%)	ACR50 (%)	ACR70 (%)	Mean Change in mTSS
SPIRIT-P1 (Biologic-Naïve)	Ixekizumab 80 mg Q4W (N=107)	58	40	23	0.18
	Placebo (N=106)	30	15	6	0.51
SPIRIT-P2 (TNFi-Experienced)	Ixekizumab 80 mg Q4W (N=109)	53	35	22	N/A
	Placebo (N=105)	20	5	0	N/A
Data from week 24 of pivotal trials. ACR20/50/70: American College of Rheumatology 20%/50%/70% improvement. mTSS: modified Total Sharp Score. Q4W: every 4 weeks. 19

5.3. Axial Spondyloarthritis (axSpA)

The clinical development of Ixekizumab for axial spondyloarthritis was strategically designed through the COAST program, which comprised three distinct pivotal trials to assess efficacy across the full spectrum of the disease. This segregated approach, with separate trials for different patient populations, allowed for the generation of high-quality, specific evidence for each clinical scenario, providing clear guidance for regulatory agencies and practicing clinicians.

• COAST-V (NCT02696785) evaluated Ixekizumab in biologic-naïve patients with radiographic axSpA (r-axSpA), also known as ankylosing spondylitis (AS).[52]
• COAST-W (NCT02696798) evaluated Ixekizumab in patients with r-axSpA who had an inadequate response or intolerance to TNF inhibitors.[52]
• COAST-X (NCT02757352) evaluated Ixekizumab in biologic-naïve patients with non-radiographic axSpA (nr-axSpA), a form of the disease where definitive structural damage is not yet visible on X-rays.[54]

The primary endpoint for these trials was the proportion of patients achieving an Assessment of SpondyloArthritis international Society 40% (ASAS40) response at week 16. As shown in Table 4, Ixekizumab demonstrated statistically significant efficacy compared to placebo in all three distinct patient populations. The COAST-Y extension study confirmed that these clinical improvements were sustained for up to 3 years with continued treatment.[56] This comprehensive program established Ixekizumab as an effective treatment option for patients across the entire axSpA spectrum, regardless of their prior treatment history or radiographic status.

Trial	Patient Population	Treatment Arm	ASAS40 Response (%)
COAST-V	r-axSpA (Biologic-Naïve)	Ixekizumab 80 mg Q4W (N=81)	48
		Placebo (N=87)	18
COAST-W	r-axSpA (TNFi-Experienced)	Ixekizumab 80 mg Q4W (N=114)	25
		Placebo (N=104)	13
COAST-X	nr-axSpA (Biologic-Naïve)	Ixekizumab 80 mg Q4W (N=96)	35
		Placebo (N=105)	19
Data from week 16 of pivotal trials. ASAS40: Assessment of SpondyloArthritis international Society 40% improvement. r-axSpA: radiographic axial spondyloarthritis. nr-axSpA: non-radiographic axial spondyloarthritis. Q4W: every 4 weeks. 19

Section 6: Comprehensive Safety and Tolerability Analysis

6.1. Overview of the Safety Profile

The safety and tolerability of Ixekizumab have been extensively evaluated in a large clinical development program and through post-marketing surveillance. Integrated safety analyses, encompassing data from 25 randomized clinical trials and over 22,000 patient-years of exposure, have established a consistent and well-characterized safety profile across all approved indications.[60] The majority of treatment-emergent adverse events (TEAEs) are mild to moderate in severity, and the incidence rates of these events have been observed to either decrease or remain stable over time with long-term exposure, with no new or unexpected safety signals identified.[12] Notably, the prescribing information for Ixekizumab does not include a boxed warning, often referred to as a "black box warning," which is the U.S. Food and Drug Administration's most stringent warning for drugs with serious or life-threatening risks.[20]

6.2. Common and Serious Adverse Events

The most frequently observed adverse reactions in clinical trials are summarized in Table 5. Injection site reactions (ISRs) are the most common TEAE, characterized primarily by erythema and pain.[66] These reactions are typically mild to moderate, occur most frequently within the first few weeks of treatment, and rarely lead to discontinuation of the drug.[69] Upper respiratory tract infections, including nasopharyngitis, are also common but are generally not serious.[1]

Adverse Reaction	Ixekizumab 80 mg Q2W (%) (N=1167)	Placebo (%) (N=791)
Injection site reactions	17	3
Upper respiratory tract infections	14	13
Nausea	2	1
Tinea infections	2	<1
Incidence of common adverse reactions occurring in ≥1% of patients in placebo-controlled plaque psoriasis trials through Week 12. 20

The overall rate of serious adverse events (SAEs) is low and comparable to placebo in short-term trials.[42] Serious infections have occurred but are infrequent. In the 12-week placebo-controlled period of the psoriasis trials, the rate of serious infections was 0.4% in both the Ixekizumab and placebo groups.[34]

6.3. Warnings and Precautions

The safety profile of Ixekizumab exhibits a "mechanistic signature," where the adverse events of special interest are a direct and predictable consequence of its targeted inhibition of the IL-17A pathway. This understanding allows for proactive risk management and patient selection.

Infections: As IL-17A is a key cytokine in mucosal immunity and defense against certain pathogens, its inhibition may increase the risk of infections.[4] The overall rate of infections was slightly higher in the Ixekizumab group compared to placebo in clinical trials (e.g., 27% vs. 23% in psoriasis trials).[20] A particular consideration is the increased risk of mucocutaneous candidiasis (fungal infections), which is consistent with the known role of IL-17A in antifungal defense.[12] These infections are typically mild to moderate and respond to standard antifungal treatment without requiring discontinuation of Ixekizumab.[12] Due to the risk of more serious infections, all patients should be evaluated for tuberculosis (TB) infection prior to initiating therapy. Ixekizumab should not be administered to patients with active TB, and treatment for latent TB infection should be initiated before starting the drug.[4]

Hypersensitivity: Serious hypersensitivity reactions, although rare (≤0.1%), have been reported, including cases of anaphylaxis, angioedema, and urticaria.[5] If a serious reaction occurs, Ixekizumab must be discontinued immediately and appropriate medical therapy initiated.[5]

Inflammatory Bowel Disease (IBD): The role of the IL-17 pathway in the gut is complex; while it can be pathogenic, it also contributes to maintaining mucosal barrier integrity. Inhibition of this pathway has been associated with new onset or exacerbation of IBD (Crohn's disease and ulcerative colitis). In clinical trials, these events occurred at a low but greater frequency in the Ixekizumab groups compared to placebo.[5] Therefore, caution is advised when prescribing Ixekizumab to patients with a history of IBD, and they should be monitored closely for signs and symptoms.[5]

Eczematous Eruptions: In the post-marketing setting, cases of severe eczematous eruptions, including atopic dermatitis-like reactions, have been reported. The onset can be variable, and some cases have required hospitalization and discontinuation of treatment.[11]

6.4. Contraindications

The use of Ixekizumab is contraindicated in patients with a history of a previous serious hypersensitivity reaction, such as anaphylaxis, to the active substance or to any of the excipients in the formulation.[5] Additionally, it should not be initiated in patients with any clinically important active infection.[27]

6.5. Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity, which is the development of anti-drug antibodies (ADAs). In a 60-week clinical study, approximately 22% of patients treated with Ixekizumab developed treatment-emergent ADAs (TE-ADAs).[36] The clinical relevance of these antibodies is dependent on their titer and neutralizing capacity. The majority of patients who developed TE-ADAs had low to moderate titers, which had a negligible impact on drug concentrations, efficacy, or safety.[79] However, a small subset of patients (approximately 2.4% of the total population) developed high-titer ADAs. In some of these individuals, high titers were associated with lower drug concentrations and a reduced clinical response.[36] Neutralizing antibodies, which directly interfere with the drug's binding to its target, were detected in approximately 2% of all patients treated with the recommended dosing regimen and were associated with loss of efficacy.[36]

Section 7: Dosing, Administration, and Drug Interactions

7.1. Recommended Dosing Regimens

The dosing of Ixekizumab is specific to the indication and, in the case of pediatric psoriasis, the patient's body weight. The regimens typically involve a higher initial or "loading" dose to rapidly achieve therapeutic concentrations, followed by a lower, less frequent "maintenance" dose. The recommended dosing schedules are detailed in Table 6.

Indication	Patient Population	Loading Dose (Week 0)	Induction Dose	Maintenance Dose
Plaque Psoriasis	Adults (≥18 years)	160 mg (two 80 mg injections)	80 mg every 2 weeks (Weeks 2-12)	80 mg every 4 weeks
	Pediatrics (>50 kg)	160 mg (two 80 mg injections)	N/A	80 mg every 4 weeks
	Pediatrics (25-50 kg)	80 mg	N/A	40 mg every 4 weeks
	Pediatrics (<25 kg)	40 mg	N/A	20 mg every 4 weeks
Psoriatic Arthritis	Adults (≥18 years)	160 mg (two 80 mg injections)	N/A	80 mg every 4 weeks*
Ankylosing Spondylitis	Adults (≥18 years)	160 mg (two 80 mg injections)	N/A	80 mg every 4 weeks
Non-radiographic Axial Spondyloarthritis	Adults (≥18 years)	N/A	N/A	80 mg every 4 weeks
*For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, the adult plaque psoriasis dosing regimen is recommended. 4

7.2. Administration and Handling

Ixekizumab is intended for subcutaneous injection and is supplied in single-dose pre-filled autoinjectors and pre-filled syringes for ease of use.[5] After receiving proper training from a healthcare professional, patients or their caregivers may administer the injections at home.[71]

The medication should be stored under refrigeration at 2°C to 8°C (36°F to 46°F) in its original carton to protect it from light. It must not be frozen.[4] Prior to injection, the device should be removed from the refrigerator and allowed to warm to room temperature for 30 minutes.[74] The solution should be inspected visually; it should be clear and colorless to slightly yellow and should not be used if it is cloudy, discolored, or contains visible particles.[20]

Recommended injection sites include the front of the thighs, the abdomen (at least one inch away from the navel), or the outer part of the upper arms (which may require assistance from a caregiver).[27] To minimize local skin reactions, injection sites should be rotated with each dose. Injections should not be administered into areas where the skin is tender, bruised, red, hard, or affected by psoriasis plaques, scars, or stretch marks.[4]

7.3. Drug Interactions

Live Vaccines: A significant interaction exists with live vaccines. Because Ixekizumab modulates the immune system, it may diminish the protective immune response to vaccinations and increase the risk of infection from live attenuated pathogens. Therefore, the use of live vaccines is contraindicated or should be avoided in patients being treated with Ixekizumab.[5] It is recommended that patients complete all age-appropriate immunizations according to current guidelines prior to initiating therapy.[28]

Other Immunosuppressive Agents: Co-administration with other immunosuppressive drugs may potentiate the risk of adverse effects, particularly infections. Caution is advised when combining Ixekizumab with agents such as aldesleukin, alefacept, azathioprine, or tofacitinib.[1]

Cytochrome P450 Substrates: Ixekizumab is not metabolized by CYP450 enzymes. However, the levels of these enzymes can be altered by chronic inflammation. Pro-inflammatory cytokines, including IL-17A, can suppress the expression of CYP enzymes. By neutralizing IL-17A and reducing inflammation, Ixekizumab could theoretically reverse this suppression, leading to a normalization of CYP activity. This could potentially decrease the serum concentrations of co-administered drugs that are substrates for these enzymes (e.g., warfarin, cyclosporine).[13] While this was an initial theoretical concern that prompted a post-marketing study recommendation [91], subsequent clinical drug interaction studies have shown no clinically significant changes in the exposure of substrates for CYP1A2, CYP2C9, CYP2C19, or CYP3A4 when co-administered with Ixekizumab.[34]

Section 8: Regulatory and Developmental Landscape

8.1. Regulatory Approval History

Ixekizumab has undergone a phased regulatory approval process, beginning with its initial indication for plaque psoriasis and progressively expanding to include other related inflammatory conditions in both adult and pediatric populations.

U.S. Food and Drug Administration (FDA):

• March 2016: The FDA granted initial approval for the treatment of adults with moderate-to-severe plaque psoriasis.[15]
• December 2017: The indication was expanded to include the treatment of adults with active psoriatic arthritis.[13]
• May 2018: A label update was approved to include specific data on the efficacy of Ixekizumab in treating psoriasis involving the genital area, a first for any psoriasis treatment.[24]
• August 2019: Approval was granted for the treatment of adults with active ankylosing spondylitis (radiographic axial spondyloarthritis).[24]
• March 2020: The plaque psoriasis indication was expanded to include pediatric patients aged 6 years and older.[24]
• June 2020: Ixekizumab became the first IL-17A antagonist to be approved by the FDA for the treatment of adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation.[24]
• August 2022: The availability of the new citrate-free formulation, designed to reduce injection site pain, was announced.[24]

European Medicines Agency (EMA):

• February 2016: The Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the treatment of moderate-to-severe plaque psoriasis in adults.[44]
• April 2016: The European Commission granted marketing authorisation for plaque psoriasis throughout the European Union.[13]
• January 2018: The indication was expanded to include the treatment of active psoriatic arthritis in adults who have had an inadequate response to or are intolerant of one or more DMARDs.[96]
• August 2019: The drug was licensed for the treatment of ankylosing spondylitis.[97]
• June 2020: The label was expanded to include pediatric plaque psoriasis (in children from age 6 with a body weight of at least 25 kg) and non-radiographic axial spondyloarthritis.[19]

8.2. Ongoing Research and Investigational Uses

The established role of IL-17A in a variety of inflammatory processes has prompted the investigation of Ixekizumab for indications beyond its currently approved uses. This ongoing research explores the potential of IL-17A inhibition in a broader range of pathologies.

A particularly novel area of investigation is the potential role of Ixekizumab in treating Major Depressive Disorder (MDD). This research is grounded in the "inflammatory hypothesis of depression," which posits that systemic inflammation, driven by cytokines like IL-17A, can contribute to the development and persistence of depressive symptoms, potentially through effects on neuroinflammatory pathways. A Phase 2 clinical trial (NCT04979910) designed to evaluate the efficacy of targeting IL-17A in patients with treatment-resistant depression has been completed, representing a fascinating bridge between the fields of immunology and neuropsychiatry.[100] The outcome of this research could significantly expand the understanding of depression's biological underpinnings and open new therapeutic avenues.

Other investigational uses include:

• Type 1 Diabetes: A Phase 2 trial, the Ixekizumab Diabetes Intervention Trial (I-DIT, NCT04589325), is actively recruiting patients to explore whether inhibiting IL-17A can intervene in the autoimmune destruction of pancreatic beta cells that characterizes this disease.[101]
• Other Dermatological Conditions: Phase II trials have been conducted to evaluate the potential of Ixekizumab in treating other severe skin diseases, including bullous pemphigoid, pityriasis rubra pilaris, and pyoderma gangrenosum.[14]
• Discontinued Indications: While the IL-17A pathway is implicated in rheumatoid arthritis, the clinical development of Ixekizumab for this indication was discontinued.[1]

Section 9: Conclusion and Expert Synthesis

9.1. Summary of Therapeutic Profile

Ixekizumab (Taltz®) is a precisely engineered, humanized IgG4 monoclonal antibody that functions as a highly specific and potent antagonist of the pro-inflammatory cytokine Interleukin-17A. Its molecular design, which includes an IgG4 backbone and stabilizing modifications, ensures a focus on pure neutralization of its target without engaging undesirable immune effector functions. The drug's extremely high binding affinity for IL-17A is a key pharmacodynamic feature that translates directly into a rapid onset of clinical action and a profound degree of efficacy.

The pharmacokinetic profile of Ixekizumab is characterized by its predictability, with linear kinetics and a long half-life of approximately 13 days that supports intermittent subcutaneous dosing. Its clearance via general protein catabolism obviates the need for dose adjustments based on renal or hepatic function, simplifying its clinical application.

A robust and extensive Phase III clinical development program has unequivocally established its efficacy across a range of autoimmune diseases. In plaque psoriasis, it has set a new benchmark for treatment success by demonstrating the ability to achieve complete skin clearance (PASI 100) in a substantial proportion of patients, with durable responses lasting for at least five years. In psoriatic arthritis and the full spectrum of axial spondyloarthritis, it has proven effective in improving joint and axial symptoms, enhancing physical function, and inhibiting structural damage progression in both biologic-naïve and treatment-experienced populations.

The safety profile is well-characterized and considered manageable. The primary risks, including an increased incidence of mucocutaneous candidiasis and a potential for the onset or exacerbation of inflammatory bowel disease, are direct consequences of its specific mechanism of action. Proactive screening for tuberculosis and avoidance of live vaccines are essential risk mitigation strategies.

9.2. Positioning in the Therapeutic Armamentarium

Based on its comprehensive profile of high efficacy, rapid action, and a well-defined safety profile, Ixekizumab is firmly positioned as a key therapeutic option for its approved indications. For patients with moderate-to-severe plaque psoriasis, it is a valuable first-line biologic therapy, particularly for those in whom complete or near-complete skin clearance is a primary treatment goal. For psoriatic arthritis and axial spondyloarthritis, it serves as an important option for both biologic-naïve patients and those who have had an inadequate response to TNF inhibitors, providing an alternative mechanism of action for a difficult-to-treat population. The development of a citrate-free formulation to improve patient comfort and reduce injection site pain further enhances its utility and potential for long-term adherence.[22]

9.3. Future Directions and Unanswered Questions

The therapeutic journey of Ixekizumab is ongoing. The investigation into novel indications, most notably Major Depressive Disorder and Type 1 Diabetes, highlights the expanding scientific interest in the role of the IL-17A pathway beyond its established role in rheumatologic and dermatologic diseases.[100] The results of these trials are eagerly awaited and could open entirely new fields of application for this class of drugs.

Within its current indications, several questions remain. While long-term safety data are reassuring, continued post-marketing surveillance is necessary to monitor for any very rare adverse events that may only become apparent with even larger patient exposures over longer timeframes. The therapeutic landscape is becoming increasingly crowded with highly effective biologics, including inhibitors of other pathways such as IL-23. Future head-to-head comparative effectiveness trials will be crucial for helping clinicians and health systems better define the optimal sequencing and positioning of these agents in personalized treatment algorithms. Finally, as more patients achieve long-term states of remission or minimal disease activity, research into treatment optimization strategies, such as dose tapering or withdrawal, will become increasingly important to balance sustained efficacy with long-term safety and cost-effectiveness.[102]

Works cited

1. Ixekizumab: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed August 3, 2025, https://go.drugbank.com/drugs/DB11569
2. Taltz Generic Name: Ixekizumab Manufacturer [1]: Eli Lilly and Company Drug Class [1]: Humanized monoclonal antibody - WVU School of Pharmacy, accessed August 3, 2025, https://pharmacy.hsc.wvu.edu/media/2802/taltz-ixekizumab.pdf
3. Ixekizumab - Versus Arthritis, accessed August 3, 2025, https://versusarthritis.org/about-arthritis/treatments/drugs/ixekizumab/
4. Ixekizumab - Arthritis Foundation, accessed August 3, 2025, https://www.arthritis.org/drug-guide/biologics/ixekizumab-(1)
5. Ixekizumab: Uses, Dosage, Side Effects, Warnings - Drugs.com, accessed August 3, 2025, https://www.drugs.com/ixekizumab.html
6. Ankylosing Spondylitis Biologic Medication | Taltz® (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/ankylosing-spondylitis
7. Taltz (Ixekizumab) Injection: Uses & Side Effects - Cleveland Clinic, accessed August 3, 2025, https://my.clevelandclinic.org/health/drugs/19888-ixekizumab-injection
8. my.clevelandclinic.org, accessed August 3, 2025, https://my.clevelandclinic.org/health/drugs/19888-ixekizumab-injection#:~:text=Taltz%C2%AE%20is%20a%20brand,take%20this%20medication%20at%20home.
9. Ixekizumab (Taltz) - American College of Rheumatology, accessed August 3, 2025, https://rheumatology.org/patients/ixekizumab-taltz
10. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A - PMC, accessed August 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4846058/
11. Mechanism of Action | IL-17A & IgG4 | Taltz (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/hcp/moa-il17a-igg4
12. Drug safety evaluation of ixekizumab for psoriasis: a review of the current knowledge - Taylor & Francis Online, accessed August 3, 2025, https://www.tandfonline.com/doi/pdf/10.1080/14740338.2022.2134855
13. Ixekizumab - Wikipedia, accessed August 3, 2025, https://en.wikipedia.org/wiki/Ixekizumab
14. Ixekizumab - Eli Lilly and Company - AdisInsight - Springer, accessed August 3, 2025, https://adisinsight.springer.com/drugs/800029418
15. 125521Orig1s000 | FDA, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125521Orig1s000Approv.pdf
16. What is the mechanism of action of Ixekizumab? - Patsnap Synapse, accessed August 3, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-action-of-ixekizumab
17. Attachment: Product Information: Ixekizumab - Therapeutic Goods Administration (TGA), accessed August 3, 2025, https://www.tga.gov.au/sites/default/files/auspar-ixekizumab-181119-pi.pdf
18. en.wikipedia.org, accessed August 3, 2025, https://en.wikipedia.org/wiki/Ixekizumab#:~:text=and%20prefilled%20syringes.-,Chemistry,the%20asparagine%20in%20position%20296.
19. Taltz, INN-ixekizumab - EMA, accessed August 3, 2025, https://www.ema.europa.eu/en/documents/product-information/taltz-epar-product-information_en.pdf
20. Reference ID: 3906227 This label may not be the latest approved by FDA. For current labeling information, please visit https:// - accessdata.fda.gov, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125521s000lbl.pdf
21. WO2020172002A1 - Therapeutic antibody formulation - Google Patents, accessed August 3, 2025, https://patents.google.com/patent/WO2020172002A1/en
22. Plaque Psoriasis (PsO) Dosing Schedule & Devices | Taltz (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/hcp/dermatology/dosing-schedule
23. What is the approval history and clinical development pathway of Taltz? - Patsnap Synapse, accessed August 3, 2025, https://synapse.patsnap.com/article/what-is-the-approval-history-and-clinical-development-pathway-of-taltz
24. Taltz (ixekizumab) FDA Approval History - Drugs.com, accessed August 3, 2025, https://www.drugs.com/history/taltz.html
25. Taltz - EMA, accessed August 3, 2025, https://www.ema.europa.eu/en/documents/procedural-steps-after/taltz-epar-procedural-steps-taken-scientific-information-after-authorisation-archive_en.pdf
26. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/27143947/
27. Ixekizumab - StatPearls - NCBI Bookshelf, accessed August 3, 2025, https://www.ncbi.nlm.nih.gov/books/NBK431088/
28. Ixekizumab Monograph for Professionals - Drugs.com, accessed August 3, 2025, https://www.drugs.com/monograph/ixekizumab.html
29. Ixekizumab competes with IL-17RA binding to immobilized human... - ResearchGate, accessed August 3, 2025, https://www.researchgate.net/figure/Ixekizumab-competes-with-IL-17RA-binding-to-immobilized-human-IL-17A-Notes-Human-IL-17A_fig2_301538785
30. Anti-Human IL-17A (Ixekizumab) - Leinco Technologies, accessed August 3, 2025, https://www.leinco.com/p/anti-human-il-17a-ixekizumab/
31. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1 - Annals of the Rheumatic Diseases, accessed August 3, 2025, https://ard.bmj.com/content/76/1/79
32. Taltz | European Medicines Agency (EMA), accessed August 3, 2025, https://www.ema.europa.eu/en/medicines/human/EPAR/taltz
33. Ixekizumab Injection: MedlinePlus Drug Information, accessed August 3, 2025, https://medlineplus.gov/druginfo/meds/a616025.html
34. This label may not be the latest approved by FDA. For current ..., accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125521s024lbl.pdf
35. Ixekizumab: A Breakthrough in Dermatologic Treatment - Number Analytics, accessed August 3, 2025, https://www.numberanalytics.com/blog/ixekizumab-dermatologic-pharmacology-guide
36. FDA Approves Taltz - American College of Clinical Pharmacology, accessed August 3, 2025, https://accp1.org/Members/ACCP1/5Publications_and_News/FDA_Approves_Taltz.aspx
37. Population pharmacokinetic and exposure-efficacy analysis of ixekizumab in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS) - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/34378230/
38. Population pharmacokinetic and exposure–efficacy analysis of ixekizumab in paediatric patients with moderate‐to‐severe plaque psoriasis (IXORA‐PEDS) - PubMed Central, accessed August 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9291793/
39. Treatment Efficacy | Dermatology | Taltz (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/hcp/dermatology/efficacy
40. Ixekizumab treatment and the impact on SF-36: results from three pivotal phase III randomised controlled trials in patients with moderate-to-severe plaque psoriasis - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/31655974/
41. Key clinical-trial evidence for ixekizumab - DermNet, accessed August 3, 2025, https://dermnetnz.org/topics/key-clinical-trial-evidence-for-ixekizumab
42. Results - Clinical Review Report: Ixekizumab (Taltz) - NCBI Bookshelf, accessed August 3, 2025, https://www.ncbi.nlm.nih.gov/books/NBK533698/
43. FDA approves new psoriasis drug Taltz, accessed August 3, 2025, https://www.fda.gov/news-events/press-announcements/fda-approves-new-psoriasis-drug-taltz
44. Lilly Receives Positive CHMP Opinion for Ixekizumab for the Treatment of Moderate-to-Severe Plaque Psoriasis, accessed August 3, 2025, https://investor.lilly.com/news-releases/news-release-details/lilly-receives-positive-chmp-opinion-ixekizumab-treatment
45. Study of Ixekizumab (LY2439821) in Children 6 to Less Than 18 Years With Moderate-to-Severe Plaque Psoriasis (Ixora-peds) - ClinicalTrials.gov, accessed August 3, 2025, https://clinicaltrials.gov/study/NCT03073200
46. Lilly Presents Positive Results for Taltz® (ixekizumab) in Pediatric Patients with Moderate to Severe Plaque Psoriasis at the 28th Annual European Academy of Dermatology and Venereology (EADV) Congress, accessed August 3, 2025, https://investor.lilly.com/news-releases/news-release-details/lilly-presents-positive-results-taltzr-ixekizumab-pediatric
47. The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2 - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/37645684/
48. A Study of Ixekizumab in Participants With Active Psoriatic Arthritis | ClinicalTrials.gov, accessed August 3, 2025, https://clinicaltrials.gov/study/NCT01695239?tab=results
49. Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1) | Rheumatology | Oxford Academic, accessed August 3, 2025, https://academic.oup.com/rheumatology/article/59/10/2774/5730209
50. Ixekizumab Shows Promise Treating Psoriatic Arthritis - Pharmacy Times, accessed August 3, 2025, https://www.pharmacytimes.com/view/ixekizumab-shows-promise-treating-psoriatic-arthritis
51. Clinical Trial of Ixekizumab for Psoriatic Arthritis Shows Positive Results, accessed August 3, 2025, https://www.the-rheumatologist.org/article/clinical-trial-ixekizumab-psoriatic-arthritis-shows-positive-results/
52. Taltz® (ixekizumab) Now FDA Approved for Ankylosing Spondylitis (or Radiographic Axial Spondyloarthritis.), accessed August 3, 2025, https://spondylitis.org/research-new/taltz-ixekizumab-now-fda-approved-for%E2%80%AFankylosing-spondylitis-or-radiographic-axial-spondyloarthritis/
53. Ixekizumab Improves Outcomes of Ankylosing Spondylitis - The Rheumatologist, accessed August 3, 2025, https://www.the-rheumatologist.org/article/ixekizumab-improves-outcomes-of-ankylosing-spondylitis/
54. A Study of Ixekizumab (LY2439821) in Participants With Nonradiographic Axial Spondyloarthritis (COAST-X) - ClinicalTrials.gov, accessed August 3, 2025, https://clinicaltrials.gov/study/NCT02757352
55. Ixekizumab for patients with non-radiographic axial spondyloarthritis (COAST-X): a randomised, placebo-controlled trial - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/31813637/
56. Long-Term Safety and Efficacy of Ixekizumab in Patients With Axial Spondyloarthritis: 3-year Data From the COAST Program | The Journal of Rheumatology, accessed August 3, 2025, https://www.jrheum.org/content/50/8/1020
57. Efficacy and safety of ixekizumab treatment in patients with axial spondyloarthritis: 2-year results from COAST - PubMed Central, accessed August 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9301795/
58. Lilly Receives U.S. FDA Approval for Taltz® (ixekizumab) for the Treatment of Active Ankylosing Spondylitis (Radiographic Axial Spondyloarthritis), accessed August 3, 2025, https://investor.lilly.com/news-releases/news-release-details/lilly-receives-us-fda-approval-taltzr-ixekizumab-treatment
59. Ixekizumab (Taltz®) shows promise in treating non-radiographic axial spondyloarthritis - Spondylitis Association of America, accessed August 3, 2025, https://spondylitis.org/research-new/ixekizumab-taltz-shows-promise-in-treating-non-radiographic-axial-spondyloarthritis/
60. Safety of ixekizumab in patients with psoriatic arthritis: data from four clinical trials with over 2000 patient-years of exposure | Annals of the Rheumatic Diseases, accessed August 3, 2025, https://ard.bmj.com/content/81/7/944
61. Ixekizumab Demonstrates Consistent Safety Profile in Long-Term Analysis - HCPLive, accessed August 3, 2025, https://www.hcplive.com/view/ixekizumab-demonstrates-consistent-safety-profile-in-long-term-analysis
62. Long-term safety of Ixekizumab in adults with psoriasis, psoriatic arthritis, or axial spondyloarthritis: a post-hoc analysis of final safety data from 25 randomized clinical trials - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/38347650/
63. Safety Data | Dermatology | Taltz (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/hcp/dermatology/safety
64. taltz.lilly.com, accessed August 3, 2025, https://taltz.lilly.com/hcp/rheumatology/safety#:~:text=No%20boxed%20warnings%20or%20routine%20lab%20monitoring%20required.&text=During%20Taltz%20treatment%2C%20monitor%20patients,exacerbation%20of%20inflammatory%20bowel%20disease.
65. Safety Data | Rheumatology PsA | Taltz (ixekizumab) - Eli Lilly, accessed August 3, 2025, https://taltz.lilly.com/hcp/rheumatology/safety
66. Label: TALTZ- ixekizumab injection, solution - DailyMed, accessed August 3, 2025, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ac96658a-d7dc-4c7c-8928-2adcdf4318b2
67. Biologic Injection Medication | PsO, PsA & axSpA | Taltz® (ixekizumab), accessed August 3, 2025, https://taltz.lilly.com/
68. Taltz (ixekizumab): Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD, accessed August 3, 2025, https://www.webmd.com/drugs/2/drug-171403/taltz-autoinjector-subcutaneous/details
69. Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials - JDDonline, accessed August 3, 2025, https://jddonline.com/articles/safety-and-tolerability-of-ixekizumab-integrated-analysis-of-injection-site-reactions-from-11-clinic-S1545961618P0200X
70. TALTZ (ixekizumab) injection, for subcutaneous use - accessdata.fda.gov, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125521s032lbl.pdf
71. TALTZ (ixekizumab) injection, for subcutaneous use - accessdata.fda.gov, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125521s004lbl.pdf
72. Lilly's Taltz® (ixekizumab) Receives the First U.S. FDA Approval for Label Update to Include Data for Psoriasis Involving the Genital Area, accessed August 3, 2025, https://investor.lilly.com/news-releases/news-release-details/lillys-taltzr-ixekizumab-receives-first-us-fda-approval-label
73. Ixekizumab (subcutaneous route) - Side effects & dosage - Mayo Clinic, accessed August 3, 2025, https://www.mayoclinic.org/drugs-supplements/ixekizumab-subcutaneous-route/description/drg-20311588
74. TALTZ (ixekizumab) injection, for subcutaneous use - This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125521s020lbl.pdf
75. Ixekizumab Side Effects: Common, Severe, Long Term - Drugs.com, accessed August 3, 2025, https://www.drugs.com/sfx/ixekizumab-side-effects.html
76. Taltz® (Ixekizumab) Summary of Risk Management Plan (RMP) - Swissmedic, accessed August 3, 2025, https://www.swissmedic.ch/dam/swissmedic/en/dokumente/marktueberwachung/rmp/ixekizumab_taltzrmpsummary.pdf.download.pdf/ixekizumab_taltzrmpsummary.pdf
77. Taltz interactions: Other drugs, alcohol, vaccines, and more - Medical News Today, accessed August 3, 2025, https://www.medicalnewstoday.com/articles/drugs-taltz-interactions
78. Taltz Injection: Uses, Side Effects & more - Drugs.com, accessed August 3, 2025, https://www.drugs.com/taltz.html
79. Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate-to-Severe Plaque Psoriasis - ResearchGate, accessed August 3, 2025, https://www.researchgate.net/publication/325026589_Ixekizumab_Pharmacokinetics_Anti-Drug_Antibodies_and_Efficacy_through_60_Weeks_of_Treatment_of_Moderate-to-Severe_Plaque_Psoriasis
80. Ixekizumab Pharmacokinetics, Anti-Drug Antibodies, and Efficacy through 60 Weeks of Treatment of Moderate to Severe Plaque Psoriasis - PubMed, accessed August 3, 2025, https://pubmed.ncbi.nlm.nih.gov/29751001/
81. Taltz (ixekizumab) dosing, indications, interactions, adverse effects, and more, accessed August 3, 2025, https://reference.medscape.com/drug/taltz-ixekizumab-1000058
82. Taltz Dosage Guide - Drugs.com, accessed August 3, 2025, https://www.drugs.com/dosage/taltz.html
83. Ixekizumab Dosage Guide + Max Dose, Adjustments - Drugs.com, accessed August 3, 2025, https://www.drugs.com/dosage/ixekizumab.html
84. Taltz's (Ixekizumab) Dosage: What to Know - Healthgrades Health Library, accessed August 3, 2025, https://resources.healthgrades.com/drugs/taltz-dosage
85. Common Dosage Recommendations for Taltz - GoodRx, accessed August 3, 2025, https://www.goodrx.com/taltz/dosage
86. TALTZ® ixekizumab injection, for subcutaneous use - This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatfda, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125521s016lbl.pdf
87. Ixekizumab: Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed August 3, 2025, https://www.rxlist.com/ixekizumab/generic-drug.htm
88. Taltz Interactions: Alcohol, Medications, and Others - Healthline, accessed August 3, 2025, https://www.healthline.com/health/drugs/taltz-interactions
89. Taltz Interactions Checker - Drugs.com, accessed August 3, 2025, https://www.drugs.com/drug-interactions/ixekizumab,taltz.html
90. Taltz (ixekizumab) Side Effects, Warnings, and Drug Interactions - MedicineNet, accessed August 3, 2025, https://www.medicinenet.com/taltz_ixekizumab_warnings_drug_interactions/side-effects.htm
91. 125521Orig1s000 - accessdata.fda.gov, accessed August 3, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125521Orig1s000ClinPharmR.pdf
92. Taltz FDA Approved for Ankylosing Spondylitis (Radiographic Axial SpA) | RheumNow, accessed August 3, 2025, https://rheumnow.com/content/taltz-fda-approved-ankylosing-spondylitis-radiographic-axial-spa
93. FDA Approves Ixekizumab for Non-Radiographic Axial Spondyloarthritis - HCPLive, accessed August 3, 2025, https://www.hcplive.com/view/fda-ixekizumab-non-radiographic-axial-spondyloarthritis
94. Eli Lilly Drug Ixekizumab Receives Expanded Approval for Non-Radiographic Axial Spondyloarthritis | Docwire News, accessed August 3, 2025, https://www.docwirenews.com/post/eli-lilly-drug-ixekizumab-receives-expanded-approval-for-non-radiographic-axial-spondyloarthritis
95. Ixekizumab: Second mAb approved in 2016 - The Antibody Society, accessed August 3, 2025, https://www.antibodysociety.org/ab-news/ixekizumab-second-mab-approved-2016/
96. EU Approves Marketing for Ixekizumab in Adults with PsA - The Rheumatologist, accessed August 3, 2025, https://www.the-rheumatologist.org/article/eu-approves-marketing-ixekizumab-adults-psa/
97. Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data - PMC, accessed August 3, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC7170548/
98. Courtesy translation – only the German version is legally binding. Ixekizumab (New Therapeutic Indication: Plaque Psoriasis in, accessed August 3, 2025, https://www.g-ba.de/downloads/91-1455-569/2021-03-10_Resolution_Ixekizumab_D-570_ENG.pdf
99. This medicinal product is subject to additional monitoring. This will allow quick identification of - Taltz, INN-ixekizumab, accessed August 3, 2025, https://ec.europa.eu/health/documents/community-register/2020/20200602148236/anx_148236_en.pdf
100. Major Depressive Disorder (MDD) Completed Phase 2 Trials for Ixekizumab (DB11569), accessed August 3, 2025, https://go.drugbank.com/indications/DBCOND0030181/clinical_trials/DB11569?phase=2&status=completed
101. Diabetes Type I Recruiting Phase 2 Trials for Ixekizumab (DB11569) | DrugBank Online, accessed August 3, 2025, https://go.drugbank.com/indications/DBCOND0060837/clinical_trials/DB11569?phase=2&status=recruiting
102. Arthritis, Psoriatic Recruiting Phase 3 Trials for Ixekizumab (DB11569) | DrugBank Online, accessed August 3, 2025, https://go.drugbank.com/indications/DBCOND0000314/clinical_trials/DB11569?phase=3&status=recruiting
103. Continued Ixekizumab Therapy Proved More Effective Than Withdrawal in Patients With Psoriatic Arthritis - HCPLive, accessed August 3, 2025, https://www.hcplive.com/view/continued-ixekizumab-therapy-proved-more-effective-than-withdrawal-in-patients-with-psoriatic-arthritis