Taltz

The solution is clear and colorless to slightly yellow.
Each pre-filled pen contains 80 mg ixekizumab in 1 mL.
Ixekizumab is produced in CHO cells by recombinant DNA technology.
Excipients/Inactive Ingredients: Sodium citrate, Anhydrous citric acid, Sodium chloride, Polysorbate 80, Water for injections.

Pharmacotherapeutic group: Immunosuppressants, interleukin inhibitors. ATC code: L04AC13.
Pharmacology: Pharmacodynamics: Mechanism of action: Ixekizumab is an IgG4 monoclonal antibody that binds with high affinity (<3 pM) and specificity to interleukin 17A (both IL-17A and IL-17A/F). Elevated concentrations of IL-17A have been implicated in the pathogenesis of psoriasis by promoting keratinocyte proliferation and activation, as well as in the pathogenesis of psoriatic arthritis and axial spondyloarthritis by driving inflammation leading to erosive bone damage and pathological new bone formation. Neutralization of IL-17A by ixekizumab inhibits these actions. Ixekizumab does not bind to ligands IL-17B, IL-17C, IL-17D, IL-17E or IL-17F.
In vitro binding assays confirmed that ixekizumab does not bind to human Fcγ receptors I, IIa, and IIIa or to complement component C1q.
Pharmacodynamic effects: Ixekizumab modulates biological responses that are induced or regulated by IL-17A. Based on psoriatic skin biopsy data from a phase I study, there was a dose-related trend towards decreased epidermal thickness, number of proliferating keratinocytes, T cells, and dendritic cells, as well as reductions in local inflammatory markers from baseline to day 43. As a direct consequence treatment with ixekizumab reduces erythema, induration and desquamation present in plaque psoriasis lesions.
Ixekizumab (Taltz) has been shown to lower (within 1 week of treatment) levels of C-reactive protein, which is a marker of the inflammation.
Clinical efficacy and safety: Adult plaque psoriasis: The efficacy and safety of Ixekizumab (Taltz) were assessed in three randomized, double-blind, placebo-controlled phase III studies in adult patients (N=3,866) with moderate to severe plaque psoriasis who were candidates for phototherapy or systemic therapy (UNCOVER-1, UNCOVER-2, and UNCOVER-3).  The efficacy and safety of Ixekizumab (Taltz) were also evaluated versus etanercept (UNCOVER-2 and UNCOVER-3). Patients randomized to Ixekizumab (Taltz) who were sPGA (0,1) responders (static Physicians Global Assessment) at week 12 were re-randomized to receive placebo or Ixekizumab (Taltz) for an additional 48 weeks (UNCOVER-1 and UNCOVER-2); patients randomized to placebo, etanercept or Ixekizumab (Taltz) who were sPGA (0,1) non-responders received Ixekizumab (Taltz) for up to 48 weeks. In addition, long-term efficacy and safety were evaluated in all three studies for up to a total of 5 years in patients who participated through the entire study.
64% of the patients had received prior systemic therapy (biologic, conventional systemic or psoralen and ultraviolet A (PUVA)), 43.5% prior phototherapy, 49.3% prior conventional systemic therapy, and 26.4% prior biologic therapy. 14.9% had received at least one anti-TNF alpha agent, and 8.7% an anti-IL-12/IL-23. 23.4% of patients had a history of psoriatic arthritis at baseline.
In all three studies, the co-primary endpoints were the proportion of patients who achieved a PASI 75 response (Psoriasis Area and Severity Index) and an sPGA of 0 ("clear") or 1 ("minimal") response at week 12 versus placebo. The median baseline PASI score ranged from 17.4 to 18.3; 48.3% to 51.2% of patients had a baseline sPGA score of severe or very severe, and mean baseline itch Numeric Rating Scale (itch NRS) ranged from 6.3 to 7.1.
Clinical response at 12 weeks: UNCOVER-1 randomized 1,296 patients (1:1:1) to receive either placebo or Ixekizumab (Taltz) (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) for 12 weeks.

Click on icon to see table/diagram/image

UNCOVER-2 randomized 1,224 patients (1:2:2:2) to receive either placebo, or Ixekizumab (Taltz) (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) or etanercept 50 mg twice weekly for 12 weeks.  (See Table 2.)

Click on icon to see table/diagram/image

UNCOVER-3 randomized 1,346 patients (1:2:2:2) to receive either placebo, or Ixekizumab (Taltz) (80 mg every two or four weeks [Q2W or Q4W] following a 160 mg starting dose) or etanercept 50 mg twice weekly for 12 weeks. (See Table 3.)

Click on icon to see table/diagram/image

Ixekizumab (Taltz) was associated with a fast onset of efficacy with > 50% reduction in mean PASI by week 2 (Figure 1). The percentage of patients achieving PASI 75 was significantly greater for Ixekizumab (Taltz) compared with placebo and etanercept as early as week 1. Approximately 25% of patients treated with Ixekizumab (Taltz) achieved a PASI score <5 by week 2, more than 55% achieved the PASI score <5 by week 4, and increased to 85% by week 12 (compared to 3%, 14% and 50% for etanercept). Significant improvements in itch severity were seen at week 1 in patients treated with Ixekizumab (Taltz). (See Figure 1.)

Click on icon to see table/diagram/image

The efficacy and safety of Ixekizumab (Taltz) was demonstrated regardless of age, gender, race, body weight, PASI baseline severity, plaques location, concurrent psoriatic arthritis, and previous treatment with a biologic. Ixekizumab (Taltz) was efficacious in systemic treatment-naive, biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure patients.
For patients identified as an sPGA (0,1) non-responder to etanercept at week 12 in UNCOVER-2 (N = 200) and who were switched to Ixekizumab (Taltz) 80 mg Q4W after a 4-week washout period, 73% and 83.5% of patients were able to achieve sPGA (0,1) and PASI 75, respectively, after 12 weeks of treatment with Ixekizumab (Taltz).
In the 2 clinical studies that included an active comparator (UNCOVER-2 and UNCOVER-3), the rate of serious adverse events was 1.9% for both etanercept and for Ixekizumab (Taltz), and the rate of discontinuation due to adverse events was 1.2% for etanercept and 2.0% for Ixekizumab (Taltz). The rate of infections was 21.5% for etanercept and 26.0% for Ixekizumab (Taltz), with 0.4% being serious for etanercept and 0.5% for Ixekizumab (Taltz).
Maintenance of response at week 60 and up to 5 years:  Patients originally randomized to Ixekizumab (Taltz) and who were responders at week 12 (i.e., sPGA score of 0,1) in UNCOVER-1 and UNCOVER-2 were re-randomized to an additional 48 weeks of treatment with placebo or Ixekizumab (Taltz) (80 mg every four or twelve weeks [Q4W or Q12W]).
For sPGA (0,1) responders at week 12 re-randomized to treatment withdrawal (i.e., placebo), the median time to relapse (sPGA≥3) was 164 days in integrated UNCOVER-1 and UNCOVER-2 studies. Among these patients, 71.5% regained at least an sPGA (0,1) response within 12 weeks of restarting treatment with Ixekizumab (Taltz) 80 mg Q4W.  (See Table 4.)

Click on icon to see table/diagram/image

Ixekizumab (Taltz) was efficacious in the maintenance of response in systemic treatment-naive, biologic-naive, biologic/anti-TNF-exposed and biologic/anti-TNF-failure patients.
Significantly greater improvements at week 12 from baseline compared to placebo and etanercept were demonstrated in nail psoriasis (as measured by the Nail Psoriasis Severity Index [NAPSI]), in scalp psoriasis (as measured by Psoriasis Scalp Severity Index [PSSI]) and in palmoplantar psoriasis (as measured by Psoriasis Palmoplantar Severity Index [PPASI]) and were maintained at week 60 in patients treated with Ixekizumab (Taltz) who were sPGA (0,1) responders at week 12.
Of 591 subjects who received, Ixekizumab (Taltz) Q2W during the Induction Period then Q4W afterward in study UNCOVER 1, UNCOVER 2, and UNCOVER 3,427 subjects completed 5 years of Ixekizumab (Taltz) treatment, among those 101 patients required a dose escalation. Among the patients who completed the Week 264 assessment (N=427), 295 patients (69%), 289 patients (68%) and 205 patients (48%) were observed to have sPGA (0,1), PASI 90 and PASI 100 response, respectively, at Week 264. DLQI were collected after Induction Period in UNCOVER 1 and UNCOVER 2, 113 patients (66%) were observed to have DLQI (0,1) response.
Quality of life/patient-reported outcomes: At week 12 and across studies, Ixekizumab (Taltz) was associated with statistically significant improvement in Health-related Quality of Life as assessed by mean decrease ranges from baseline in the Dermatology Life Quality Index (DLQI) Ixekizumab (Taltz) 80 mg Q2W from -10.2 to -11.1, Ixekizumab (Taltz) 80 mg Q4W from -9.4 to -10.7, etanercept from -7.7 to -8.0 and placebo -1.0 to -2.0). A significantly greater proportion of patients treated with Ixekizumab (Taltz) achieved a DLQI 0 or 1. Across studies, a significantly greater proportion of patients treated with Ixekizumab (Taltz) achieved a reduction of Itch NRS ≥4 points at week 12 (84.6% for Ixekizumab (Taltz) Q2W, 79.2% for Ixekizumab (Taltz) Q4W and 16.5% for placebo) and the benefit was sustained over time up to week 60 in patients treated with Ixekizumab (Taltz) who were sPGA (0 or 1) responders at week 12. There was not any evidence of worsening of depression up to 60-weeks treatment with Ixekizumab (Taltz) as assessed by the Quick Inventory of Depressive Symptomatology Self Report.
Postmarketing direct comparative study: IXORA-S: In a double-blind study Ixekizumab (Taltz) was superior against ustekinumab on the primary study objective PASI 90 response at week 12 (Table 5). Onset of response was superior on PASI 75 as early as week 2 (p <0.001) and on PASI 90 and PASI 100 by week 4 (p <0.001). Superiority of Ixekizumab (Taltz) versus ustekinumab was also demonstrated in the subgroups stratified by weight. (See Table 5.)

Click on icon to see table/diagram/image

IXORA-R: Efficacy and safety of Ixekizumab (Taltz) was also investigated in a 24‑week randomized, double-blind, parallel-group study comparing Ixekizumab (Taltz) to guselkumab, with Ixekizumab (Taltz) being superior as early as week 4 in achieving complete skin clearance and on the primary study objective (PASI 100 at week 12) and non-inferior on PASI 100 at week 24 (Table 6). (See Table 6 and Figure 2).

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Efficacy in genital psoriasis: A randomized, double-blind, placebo-controlled study (IXORA-Q) was conducted in 149 adult subjects (24% females) with moderate to severe genital psoriasis (sPGA of Genitalia score of ≥3), a minimum body surface area (BSA) involvement of 1% (60.4% had a BSA ≥10%) and previous failure of or intolerance to at least one topical therapy for genital psoriasis. Patients had at least moderate plaque psoriasis (defined as sPGA score of ≥3 and being candidates for phototherapy and/or systemic therapy) for at least 6 months.
Subjects randomized to Ixekizumab (Taltz) received an initial dose of 160 mg followed by 80 mg every 2 weeks for 12 weeks. The primary endpoint was the proportion of patients who achieved at least a "0" (clear) or "1" (minimal) response on the sPGA of Genitalia (sPGA of Genitalia 0/1). At week 12, significantly more subjects in the Ixekizumab (Taltz) group than placebo group achieved a sPGA of Genitalia 0/1 and a sPGA 0/1 independent of baseline BSA (baseline BSA 1% - <10% resp. ≥10%: sPGA of Genitalia "0" or "1": Ixekizumab (Taltz) 71%, resp. 75%; placebo: 0%, resp. 13%). A significantly greater proportion of patients treated with Ixekizumab (Taltz) achieved a reduction in the PROs of severity of genital pain, genital itch, impact of genital psoriasis on sexual activity, and Dermatology Quality of Life Index (DLQI). (See Table 7.)

Click on icon to see table/diagram/image

Paediatric plaque psoriasis: A randomized, double-blind, multicenter, placebo-controlled trial (IXORA-Peds) enrolled 201 children 6 to less than 18 years of age, with moderate to severe plaque psoriasis (as defined by a sPGA score ≥3, involving ≥10% of the body surface area, and a PASI score ≥12) who were candidates for phototherapy or systemic therapy, or were inadequately controlled on topical therapy.
Patients were randomized to placebo (n=56), etanercept (n=30) or Ixekizumab (Taltz) (n=115) with dosing stratified by weight: <25 kg: 40 mg at Week 0 followed by 20 mg Q4W (n=4); 25 kg to 50 kg: 80 mg at Week 0 followed by 40 mg Q4W (n=50); >50 kg: 160 mg at Week 0 followed by 80 mg Q4W (n=147).
Patients randomized to etanercept (patients with severe psoriasis) received 0.8 mg/kg, not exceeding 50 mg per dose, every week from Week 0 through Week 11.
Response to treatment was assessed after 12 weeks of therapy and was defined by the proportion of patients who achieved the co-primary endpoint of an sPGA score of "0" (clear) or "1" (almost clear) with at least a 2 point improvement from baseline and the proportion of patients that achieved a reduction in PASI score of at least 75% (PASI 75) from baseline.
Other evaluated outcomes at Week 12 included the proportion of patients who achieved PASI 90, PASI 100, sPGA of "0" and an improvement of itch severity as measured by a reduction of at least 4 points on an 11-point itch Numeric Rating Scale.
Patients had a median baseline PASI of 17 score ranging from 12-49. Baseline sPGA score was severe or very severe in 49%. Of all patients, 22% had received prior phototherapy and 32% had received prior conventional systemic therapy for the treatment of psoriasis.
25% of patients (n=43) were below 12 years (14% of patients [n=24] were 6-9 years and 11% of patients [n=19] were 10-11 years); 75% (n=128) were 12 years or above.
The clinical response data are presented in Table 8. (See Table 8 and Figure 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Patients in the ixekizumab treatment group had clinically meaningful higher CDLQI/DLQI (0,1) responses at Week 12 (NRI) compared with placebo. The difference between treatment groups was apparent from as early as Week 4.
There were greater improvements at Week 12 from baseline compared to placebo in nail psoriasis (as measured by the Nail Psoriasis Severity Index [NAPSI=0: Ixekziumab (Taltz) 18% (6/34), placebo 0% (0/12)]), in scalp psoriasis (as measured by Psoriasis Scalp Severity Index [PSSI=0: Ixekizumab (Taltz) 69% (70/102), placebo 16% (8/50)]) and in palmoplantar psoriasis (as measured by Psoriasis Palmoplantar Severity Index [PPASI 75: Ixekizumab (Taltz) 53% (9/17), placebo 11% (1/9)]).
Psoriatic arthritis: Ixekizumab (Taltz) was assessed in two randomized, double-blind, placebo-controlled phase III studies in 780 patients with active psoriatic arthritis (≥3 swollen and ≥3 tender joints). Patients had a diagnosis of psoriatic arthritis (Classification Criteria for Psoriatic Arthritis [CASPAR] criteria) for a median of 5.33 years and had current plaque psoriasis skin lesions (94.0%) or a documented history of plaque psoriasis, with 12.1% of patients with moderate to severe plaque psoriasis at baseline. Over 58.9% and 22.3% of the psoriatic arthritis patients had enthesitis and dactylitis at baseline, respectively. Primary endpoint of both studies was American College of Rheumatology (ACR) 20 response at week 24, followed by a long-term extension period from Week 24 to Week 156 (3 years).
In Psoriatic Arthritis Study 1 (SPIRIT-P1), patients naive to biologic therapy with active psoriatic arthritis were randomized to placebo, adalimumab 40 mg once every 2 weeks (active control reference arm), Ixekizumab (Taltz) 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W). Both Ixekizumab (Taltz) regimens included a 160 mg starting dose. 85.3% of patients in this study had received prior treatment with ≥1 cDMARD. 53% of patients had concomitant use of MTX at a mean weekly dose of 15.8 mg. 67% of patients who had concomitant use of MTX had a dose of 15 mg or greater. Patients with an inadequate response at week 16 received rescue therapy (modification to background therapy). Patients on Ixekizumab (Taltz) Q2W or Q4W remained on their originally assigned dose of Ixekizumab (Taltz). Patients receiving adalimumab or placebo were re-randomized 1:1 to Ixekizumab (Taltz) Q2W or Q4W at week 16 or 24 based on responder status. 243 patients completed the extension period of 3 years on Ixekizumab (Taltz).
Psoriatic Arthritis Study 2 (SPIRIT-P2) enrolled patients who were previously treated with an anti-TNF agent and discontinued the anti-TNF agent for either lack of efficacy or intolerance (anti-TNF-IR patients). Patients were randomized to subcutaneous injections of placebo, Ixekizumab (Taltz) 80 mg once every 2 weeks (Q2W), or 80 mg once every 4 weeks (Q4W). Both Ixekizumab (Taltz) regimens included a 160 mg starting dose. 56% and 35% of patients were inadequate responders to 1 anti-TNF or 2 anti-TNF, respectively. SPIRIT-P2 evaluated 363 patients, of whom 41% had concomitant use of MTX at a mean weekly dose of 16.1 mg. 73.2% of patients who had concomitant use of MTX had a dose of 15 mg or greater. Patients with an inadequate response at week 16 received rescue therapy (modification to background therapy). Patients in Ixekizumab (Taltz) Q2W or Q4W remained on their originally assigned dose of Ixekizumab (Taltz). Patients receiving placebo were re-randomized 1:1 to Ixekizumab (Taltz) Q2W or Q4W at week 16 or 24 based on responder status. 168 patients completed the extension period of 3 years on Ixekizumab (Taltz).
Signs and symptoms: Treatment with Ixekizumab (Taltz) resulted in significant improvement in measures of disease activity compared to placebo at week 24 (see Table 9).

Click on icon to see table/diagram/image

In patients with pre-existing dactylitis or enthesitis, treatment with Ixekizumab (Taltz) Q4W resulted in improvement in dactylitis and enthesitis at week 24 compared to placebo (resolution: 78% vs. 24%; p<0.001, and 39% vs. 21%; p<0.01, respectively).
In patients with ≥3% BSA, the improvement in skin clearance at week 12 as measured by 75% improvement in Psoriasis Area Severity Index (PASI 75), was 67% (94/141) for those treated with the Q4W dosing regimen, and 9% (12/134) for those treated with placebo (p<0.001). The proportion of patients achieving a PASI 75, PASI 90, and PASI 100 response at week 24 was greater with Ixekizumab (Taltz) Q4W compared to placebo (p<0.001). In patients with concomitant moderate to severe psoriasis and psoriatic arthritis, Ixekizumab (Taltz) Q2W dose regimen showed significantly higher response rate for PASI 75, PASI 90 and PASI 100 compared to placebo (p<0.001) and demonstrated clinically meaningful benefit over the Q4W dose regimen.
Treatment responses on Ixekizumab (Taltz) were significantly greater than those on placebo as early as week 1 for ACR 20, week 4 for ACR 50 and week 8 for ACR 70 and persisted through week 24; effects were maintained through 3 years for patients who remained in the study. (See Figure 4.)

Click on icon to see table/diagram/image

In SPIRIT-P1 and SPIRIT-P2, similar responses for ACR 20/50/70 were seen in patients with psoriatic arthritis regardless of whether they were on concomitant cDMARDs, including MTX treatment, or not.
In SPIRIT-P1 and SPIRIT-P2, improvements were shown in all components of the ACR scores including patient assessment of pain. At week 24 the proportion of patients achieving a modified Psoriatic Arthritis Response Criteria (PsARC) response was greater in the Ixekizumab (Taltz)-treated patients compared to placebo.
In SPIRIT-P1, efficacy was maintained up to week 52 as assessed by ACR 20/50/70, MDA, enthesitis resolution, dactylitis resolution, and PASI 75/90/100 response rates.
The efficacy and safety of Ixekizumab (Taltz) was demonstrated regardless of age, gender, race, disease duration, baseline body weight, baseline psoriasis involvement, baseline CRP, baseline DAS28-CRP, concomitant corticosteroid use, and previous treatment with a biologic. Ixekizumab (Taltz) was efficacious in biologic-naive, biologic-exposed and biologic-failure patients.
In SPIRIT-P1, 63 patients completed 3 years of Q4W ixekizumab treatment. Among the 107 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 54 patients (50%), 41 patients (38%), 29 patients (27%), and 36 patients (34%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.
In SPIRIT-P2, 70 patients completed 3 years of Q4W ixekizumab treatment. Among the 122 patients who were randomized to ixekizumab Q4W (NRI analysis in ITT population), 56 patients (46%), 39 patients (32%), 24 patients (20%) and 33 (27%) were observed to have ACR20, ACR50, ACR70, and MDA response, respectively, at Week 156.
Radiographic response: In SPIRIT-P1, inhibition of progression of structural damage was assessed radiographically and expressed as the change in modified total Sharp Score (mTSS) and its components, the Erosion Score (ES) and the Joint Space Narrowing score (JSN) at weeks 24 and 52, compared to baseline. Week 24 data are presented in Table 10. (See Table 10.)

Click on icon to see table/diagram/image

Radiographic joint damage progression was inhibited by Ixekizumab (Taltz) (Table 10) at week 24, and the percentage of patients with no radiographic joint damage progression (defined as a change from baseline in mTSS of ≤0.5) from randomization to week 24 was 94.8% for Ixekizumab (Taltz) Q2W (p<0.001), 89.0% for Ixekizumab (Taltz) Q4W (p=0.026), 95.8% for adalimumab (p<0.001), all compared to 77.4% for placebo. At week 52, the mean change from baseline in mTSS was 0.27 for placebo/Ixekizumab (Taltz) Q4W, 0.54 for Ixekizumab (Taltz) Q4W/Ixekizumab (Taltz) Q4W, and 0.32 for adalimumab/Ixekizumab (Taltz) Q4W. The percentage of patients with no radiographic joint damage progression from randomization to week 52 was 90.9% for placebo/Ixekizumab (Taltz) Q4W, 85.6% for Ixekizumab (Taltz) Q4W/Ixekizumab (Taltz) Q4W, and 89.4% for adalimumab/Ixekizumab (Taltz) Q4W. Patients had no structural progression from baseline (defined as mTSS ≤0.5) in the treatment arms as follows: Placebo/Ixekizumab (Taltz) Q4W 81.5% (N=22/27), Ixekizumab (Taltz) Q4W/Ixekizumab (Taltz) Q4W 73.6% (N=53/72), and adalimumab/Ixekizumab (Taltz) Q4W 88.2% (N=30/34).
Physical function and health-related quality of life: In both SPIRIT-P1 and SPIRIT-P2, patients treated with Ixekizumab (Taltz) Q2W (p<0.001) and Q4W (p<0.001) showed significant improvement in physical function compared to patients treated with placebo as assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) at week 24, and maintained at Week 52 in SPIRIT-P1.
Ixekizumab (Taltz)-treated patients reported improvements in health-related quality of life as measured by the Physical Component Summary of the Short Form-36 Health Survey (SF-36 PCS) score (p<0.001). There were also improvements demonstrated in fatigue as assessed by Fatigue severity NRS scores (p<0.001).
Post-marketing phase 4, direct comparative study: Efficacy and safety of Ixekizumab (Taltz) was investigated in a multicenter, randomized, open-label, rater-blinded, parallel-group study (SPIRIT-H2H) compared to adalimumab (ADA) in 566 patients with PsA who were naïve to biologic disease-modifying anti-rheumatic drugs (bDMARD). Patients were stratified at baseline based on concomitant cDMARD use and presence of moderate-to-severe psoriasis (PASI≥12, BSA≥10 and sPGA≥3).
Ixekizumab (Taltz) was superior to ADA on the primary study objective: simultaneous achievement of ACR 50 and PASI 100 response at week 24 (Ixekizumab (Taltz) 36.0% vs ADA 27.9%; p=0.036; 95% confidence interval [0.5%, 15.8%]). Ixekizumab (Taltz) also showed non-inferiority (pre-specified margin of -12%) to ADA on ACR 50 (ITT analysis: Ixekizumab (Taltz) 50.5% vs ADA 46.6%; 3.9% difference vs. ADA; 95% confidence interval [-4.3%; 12.1%] ; PPS analysis Ixekizumab (Taltz): 52.3%, ADA: 53.1%, difference: -0.8% [CI: -10.3%; 8.7%]) and superiority on PASI 100 at week 24 (60.1 % with Ixekizumab (Taltz) vs 46.6% with ADA, p=0.001), which were the major secondary endpoints in the study. At Week 52 a higher proportion of patients treated with Ixekizumab (Taltz) versus ADA simultaneously achieved ACR50 and PASI 100 [39% (111/283) versus 26% (74/283)] and PASI 100 [64% (182/283) versus 41% (117/283)]. Ixekizumab (Taltz) and ADA treatment resulted in similar responses for ACR50 [49.8% (141/283) versus 49.8% (141/283)]. Responses to Ixekizumab (Taltz) were consistent when used as monotherapy or with concomitant use of methotrexate.  (See Figure 5.)

Click on icon to see table/diagram/image

Axial spondyloarthritis: Ixekizumab (Taltz) was assessed in a total of 960 adult patients with axial spondyloarthritis in three randomized placebo-controlled studied (two in radiographic and one in non-radiographic axial spondyloarthritis).
Radiographic axial spondyloarthritis: Ixekizumab (Taltz) was assessed in a total of 657 patients in two randomized, double blind, placebo-controlled studies (COAST-V) and COAST-W) in adult patients who had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 and total back pain ≥4 on a numeric rating scale despite non-steroidal anti-inflammatory drug (NSAID) therapy. Across both studies at baseline, patients had symptoms for a mean of 17 years (median of 16 years). At baseline, approximately 32% of the patient were on a concomitant cDMARD.
COAST-V evaluated 341 biologic-naïve patients, who were treated with either Ixekizumab (Taltz) 80 mg or 160 mg at Week 0 followed by 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), adalimumab 40 mg every 2 weeks, or with placebo. Patients receiving placebo were re-randomized at week 16 to receive Ixekizumab (Taltz) (160 mg starting dose, followed by 80 mg Q2W or Q4W). Patients receiving adalimumab were re randomized at Week 16 to receive Ixekizumab (Taltz) (80 mg Q2W or Q4W).
COAST-W evaluated 316 patients who had prior experience with 1 or 2 TNF-inhibitors (90% were inadequate responders and 10% were intolerant to TNF inhibitors). All patients were treated with Ixekizumab (Taltz) 80 or 160 mg at Week 0 followed by 80 mg Q2W or Q4W, or with placebo. Patients receiving placebo were re-randomized at Week 16 to receive Ixekizumab (Taltz) (160 mg initial dose, followed by 80 mg Q2W or Q4W).
The primary endpoint in both studies was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at week 16.
Clinical Response: In both studies, patients treated with Ixekizumab (Taltz) 80 mg Q2W or 80 mg Q4W demonstrated greater improvements in ASAS40 and ASAS20 responses compared to placebo at week 16 (Table 11). Responses were similar in patients regardless of concomitant therapies. In COAST-W, responses were seen regardless of the number of prior TNF inhibitors. (See Table 11.)

Click on icon to see table/diagram/image

There were improvements in the main components of the ASAS40 response criteria (spinal pain, BASFI, patient global assessment, stiffness) and other measures of disease activity, including CRP, at week 16. (See Figure 6.)

Click on icon to see table/diagram/image

Similar response in ASAS40 was seen in patients regardless of baseline CRP levels, baseline ASDAS scores and MRI spine SPARCC scores. The ASAS40 response was demonstrated regardless of age, gender, race, disease duration, baseline body weight, baseline BASDAI score and prior biologic treatment.
In COAST-V and COAST-W efficacy was maintained up to week 52 as assessed by the endpoints presented in Table 11, including ASAS20, ASAS40, ASDAS, BASDAI, and ASAS HI response rates.
Health-Related Outcomes: Spinal pain showed improvements versus placebo as early as week 1, maintained through week 16 [Ixekizumab (Taltz) vs placebo: COAST-V -3.2 vs -1.7; COAST-W -2.4 vs -1.0]; fatigue and spinal mobility showed improvements versus placebo at Week 16. Improvements in spinal pain, fatigue and spinal mobility were maintained through week 52.
Non-radiographic axial spondyloarthritis: Ixekizumab (Taltz) was assessed in a randomized, double-blind study with a 52-week placebo-controlled period (COAST-X) in 303 adult patients with active axial spondyloarthritis for at least 3 months. Patients must have had objective signs of inflammation indicated by elevated C-reactive protein (CRP) and/or sacroiliitis on magnetic resonance imaging (MRI), and no definitive radiographic evidence of structural damage on sacroiliac joints. Patients had active disease as defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, and spinal pain ≥4 on a 0 to 10 Numerical Rating Scale (NRS), despite non-steroidal anti-inflammatory drug (NSAID) therapy. Patients were treated with either Ixekizumab (Taltz) 80 mg or 160 mg at Week 0, followed by 80 mg every 2 weeks (Q2W) or 80 mg every 4 weeks (Q4W) or with placebo. Dose adjustment and/or initiation of concomitant medications (NSAIDs, cDMARDs, corticosteroids, analgesics) were permitted starting at week 16.
At baseline, patients had symptoms of non-radiographic axSpA for an average of 11 years. Approximately 39% of the patients were on concomitant cDMARD.
The primary endpoint was the percentage of patients achieving an Assessment of Spondyloarthritis International Society 40 (ASAS40) response at week 16.
Clinical Response: Higher proportions of patients treated with Ixekizumab (Taltz) 80 mg Q4W achieved ASAS40 response compared to placebo at Week 16 (Table 12). Responses were similar regardless of concomitant therapies. (See Table 12.)

Click on icon to see table/diagram/image

The improvement in the main components of the ASAS40 response criteria (spinal pain, BASFI, patient global assessment, stiffness) and other measures of disease activity demonstrated significant clinical improvement at week 16. (See Figure 7.)

Click on icon to see table/diagram/image

Efficacy was maintained up to week 52 as assessed by the endpoints presented in Table 12.
Health-related outcomes: Spinal pain showed improvements versus placebo as early as week 1 and was maintained through week 16 [Ixekizumab (Taltz) vs placebo; COAST-X: -2.4 vs -1.5]. In addition, more patients on Ixekizumab (Taltz) compared with placebo achieved good health status (ASAS HI ≤5) at week 16 and week 52.
Long-term outcomes Axial Spondyloarthritis: Patients who completed one of the three pivotal studies COAST-V/W/X (52 weeks) were offered participation in a long-term extension and randomised withdrawal study (COAST-Y, with 350 and 423 patients enrolled on Ixekizumab (Taltz) Q4W and Q2W, respectively). Among those who achieved remission 157/773 (20.3%) (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3 at least once, and no ASDAS score ≥2.1, at weeks 16 and 20), 155 patients exposed to Ixekizumab (Taltz) up to 76 weeks were randomised at week 24 of the COAST-Y study (Placebo, N=53; Ixekizumab (Taltz) Q4W, N=48; and Ixekizumab (Taltz) Q2W, N=54); of these, 148 (95.5%) completed the week 64 visit (Placebo, N=50; Ixekizumab (Taltz) Q4W, N=47; Ixekizumab (Taltz) Q2W, N=51). The primary endpoint was the proportion of patients in the randomised withdrawal population who did not experience a flare during weeks 24 64 (combined Ixekizumab (Taltz) Q2W and Ixekizumab (Taltz) Q4W groups versus placebo). A significantly larger proportion of patients (NRI) in the combined Ixekizumab (Taltz) groups (83.3% (85/102), p<0.001) and Ixekizumab (Taltz) Q4W (83.3 % (40/48), p=0.003) had no flare during weeks 24 64 compared with those who withdrew from Ixekizumab (Taltz) to placebo (54.7 % (29/53)). Ixekizumab (Taltz) (in both combined Ixekizumab (Taltz) groups and Ixekizumab (Taltz) Q4W group) significantly delayed the time to flare (Log Rank Test p<0.001 and p<0.01, respectively) compared to Placebo.
In patients who received Ixekizumab (Taltz) Q4W continuously (N=157), the ASAS40, ASDAS <2.1 and BASDAI50 responses were maintained to Week 116.
Immunizations: In a study in healthy subjects, no safety concerns were identified of two inactivated vaccines (tetanus and pneumococcal), received after two doses of ixekizumab (160 mg followed by a second dose of 80 mg two weeks later). However, the data concerning immunization were insufficient to conclude on an adequate immune response to these vaccines following administration of Ixekizumab (Taltz).
Pediatric population: The European Medicines Agency has deferred the obligation to submit the results of studies with Ixekizumab (Taltz) in one or more subsets of the pediatric population in the treatment of plaque psoriasis and psoriatic arthritis (see Dosage & Administration for information on pediatric use).
Pharmacokinetics: Absorption: Following a single subcutaneous dose of ixekizumab in patients with psoriasis, mean peak concentrations were achieved within 4 to 7 days, across a dose range of 5 to 160 mg. The mean (SD) maximum plasma concentration (C_max) of ixekizumab, after the 160 mg starting dose, was 19.9 (8.15) µg/mL.
After the 160 mg starting dose, steady state was achieved by week 8 with the 80 mg Q2W dosing regimen. Mean (SD) C_max,ss, and C_trough,ss estimates are 21.5 (9.16) µg/mL, and 5.23 (3.19) µg/mL.
After switching from the 80 mg Q2W dosing regimen to the 80 mg Q4W dosing regimen at week 12, steady state would be achieved after approximately 10 weeks. Mean (SD) C_max,ss, and C_trough,ss estimates are 14.6 (6.04) µg/mL, and 1.87 (1.30) µg/mL.
The average bioavailability of ixekizumab after subcutaneous administration was 54% to 90% across analyses.
Distribution: From population pharmacokinetic analyses, the mean total volume of distribution at steady state was 7.11 L.
Biotransformation: Ixekizumab is a monoclonal antibody and is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous immunoglobulins.
Elimination: In the population PK analysis, mean serum clearance was 0.0161 L/hr. Clearance is independent of dose. The mean elimination half-life, as estimated from population pharmacokinetic analysis, is 13 days in patients with plaque psoriasis.
Linearity/non-linearity: Exposure (AUC) increased proportionally over a dose range of 5 to 160 mg given as a subcutaneous injection.
Pharmacokinetic properties across indications: The pharmacokinetic properties of Ixekizumab (Taltz) were similar across the plaque psoriasis, psoriatic arthritis, radiographic axial spondyloarthritis and non-radiographic spondyloarthritis indications.
Elderly: Of the 4,204 plaque psoriasis patients exposed to Ixekizumab (Taltz) in clinical studies, a total of 301 were 65 years of age or older and 36 patients were 75 years of age or older. Of the 1,118 psoriatic arthritis patients exposed to Ixekizumab (Taltz) in clinical studies, a total of 122 patients were 65 years of age or older and 6 patients were 75 years of age or older.
Based on population pharmacokinetic analysis with a limited number of elderly patients (n=94 for age ≥65 years and n=12 for age ≥75 years), clearance in elderly patients and patients less than 65 years of age was similar.
Renal or hepatic impairment: Specific clinical pharmacology studies to evaluate the effects of renal impairment and hepatic impairment on the PK of ixekizumab have not been conducted. Renal elimination of intact ixekizumab, an IgG MAb, is expected to be low and of minor importance; similarly, IgG MAbs are mainly eliminated via intracellular catabolism and hepatic impairment is not expected to influence clearance of ixekizumab.
Paediatric Population: Paediatric psoriasis patients (age 6 to less than 18 years) were administered ixekizumab at the recommended paediatric dosing regimen for 12 weeks. Patients weighing >50 kg and 25 to 50 kg had a mean ±SD steady-state trough concentration of 3.8 ± 2.2 μg/ml and 3.9 ±2.4 μg/ml, respectively, at Week 12.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazards for humans based on repeat-dose toxicity studies, safety pharmacology evaluations, and reproductive and developmental toxicity studies.
Ixekizumab administration to cynomolgus monkeys for 39 weeks at subcutaneous doses up to 50 mg/kg weekly produced no organ toxicity or undesirable effects on immune function (e.g., T-cell dependent antibody response and NK cell activity). A weekly subcutaneous dose of 50 mg/kg to monkeys is approximately 19 times the 160 mg starting dose of Ixekizumab (Taltz) and in monkeys results in exposure (AUC) that is at least 61-fold higher than the predicted mean steady-state exposure in humans administered the recommended dose regimen.
Non-clinical studies have not been conducted to evaluate the carcinogenic or mutagenic potential of ixekizumab.
No effects on reproductive organs, menstrual cycles or sperm were observed in sexually mature cynomolgus monkeys that received ixekizumab for 13 weeks at a weekly subcutaneous dose of 50 mg/kg.
In developmental toxicity studies, ixekizumab was shown to cross the placenta and was present in the blood of offspring for up to 6 months of age. A higher incidence of postnatal mortality occurred in the offspring of monkeys given ixekizumab compared to concurrent controls. This was related primarily to early delivery or maternal neglect of offspring, common findings in nonhuman primate studies, and considered clinically irrelevant.

Plaque psoriasis: Ixekizumab (Taltz) is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Paediatric plaque psoriasis: Ixekizumab (Taltz) is indicated for the treatment of moderate to severe plaque psoriasis in children from the age of 6 years and adolescents who are candidates for systemic therapy.
Psoriatic arthritis: Ixekizumab (Taltz), alone or in combination with methotrexate, is indicated for the treatment of active psoriatic arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drug (DMARD) therapies (see Pharmacology: Pharmacodynamics under Actions).
Axial spondyloarthritis: Ankylosing spondylitis (radiographic axial spondyloarthritis): Ixekizumab (Taltz) is indicated for the treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy.
Non-radiographic axial spondyloarthritis: Ixekizumab (Taltz) is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).

This medicinal product is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which it is indicated.
Posology: Plaque psoriasis in adults: The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at week 0, followed by 80 mg (one injection) at weeks 2, 4, 6, 8, 10, and 12, then maintenance dosing of 80 mg (one injection) every 4 weeks (Q4W).
Paediatric plaque psoriasis (age 6 years and above): Efficacy and safety data is not available in children below the age of 6 years (see Pharmacology: Pharmacodynamics under Actions). Available data do not support a posology below a body weight of 25 kg.
The recommended dose given by subcutaneous injection in children is based on the following weight categories: see Table 13.

Click on icon to see table/diagram/image

Paediatric body weights must be recorded and regularly re-checked prior to dosing.
Psoriatic arthritis: The recommended dose is 160 mg by subcutaneous injection (two 80 mg injections) at week 0, followed by 80 mg (one injection) every 4 weeks thereafter. For psoriatic arthritis patients with concomitant moderate to severe plaque psoriasis, the recommended dosing regimen is the same as for plaque psoriasis.
Axial spondyloarthritis (radiographic and non-radiographic): The recommended dose is 160 mg (two 80 mg injections) by subcutaneous injection at week 0, followed by 80 mg every 4 weeks (see Pharmacology: Pharmacodynamics under Actions for further information).
For all indications (plaque psoriasis in adults and children, psoriatic arthritis, axial spondyloarthritis) consideration should be given to discontinuing treatment in patients who have shown no response after 16 to 20 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 20 weeks.
Special Populations: Elderly (≥ 65 years): No dose adjustment is required (see Pharmacology: Pharmacokinetics under Actions).
There is limited information in subjects aged ≥ 75 years.
Renal or hepatic impairment: Ixekizumab (Taltz) has not been studied in these patient populations. No dose recommendations can be made.
Pediatric population: Paediatric plaque psoriasis (below the age of 6 years): There is no relevant use of Ixekizumab (Taltz) in children below the age of 6 years in the treatment of moderate to severe plaque psoriasis.
Paediatric psoriatic arthritis: The safety and efficacy of Ixekizumab (Taltz) in children and adolescents aged 2 to less than 18 years in the treatment of psoriatic arthritis (a category of juvenile idiopathic arthritis) have not yet been established. No data are available. There is no relevant use of Ixekizumab (Taltz) in children below 2 years for the indication of psoriatic arthritis.
Method of administration: Subcutaneous use.
Ixekizumab (Taltz) is for subcutaneous injection. Injection sites may be alternated. If possible, areas of the skin that show psoriasis should be avoided as injection sites. The solution/the pen must not be shaken.
After proper training in subcutaneous injection technique, patients may self-inject Ixekizumab (Taltz) if a healthcare professional determines that it is appropriate. However, the physician should ensure appropriate follow-up of patients. Comprehensive instructions for administration are given in the package leaflet and the user manual.

Doses up to 180 mg have been administered subcutaneously in clinical trials without dose-limiting toxicity. Overdoses up to 240 mg, subcutaneously, as a single administration in clinical trials, have been reported without any serious adverse events. In the event of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.

Serious hypersensitivity to the active substance or to any of the excipients listed in Description.
Clinically important active infections (e.g., active tuberculosis, see Precautions).

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Infections: Treatment with Ixekizumab (Taltz) is associated with an increased rate of infections such as upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infections (see Adverse Reactions).
Ixekizumab (Taltz) should be used with caution in patients with clinically important chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If an infection develops, patients should be carefully monitored and Ixekizumab (Taltz) discontinued if the patient is not responding to standard therapy or if the infection becomes serious. Ixekizumab (Taltz) should not be resumed until the infection resolves.
Ixekizumab (Taltz) must not be given to patients with active tuberculosis (TB). Anti-TB therapy prior to initiation of Ixekizumab (Taltz) in patients with latent TB should be considered.
Hypersensitivity: Serious hypersensitivity reactions, including some cases of anaphylaxis, angioedema, urticaria and, rarely, late (10-14 days following injection) serious hypersensitivity reactions including widespread urticaria, dyspnea and high antibody titers have been reported. If a serious hypersensitivity reaction occurs, administration of Ixekizumab (Taltz) should be discontinued immediately and appropriate therapy initiated.
Inflammatory bowel disease (including Crohn's disease and ulcerative colitis): Cases of new or exacerbations of inflammatory bowel disease have been reported with ixekizumab (see Adverse Reactions). Ixekizumab is not recommended in patients with inflammatory bowel disease. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, ixekizumab should be discontinued and appropriate medical management should be initiated.
Immunizations: Ixekizumab (Taltz) should not be used with live vaccines. No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines (see Pharmacology: Pharmacodynamics under Actions).
Excipients: This medicinal product contains less than 1 mmol sodium (23 mg) per 80 mg dose, that is to say essentially "sodium-free".
Effects on ability to drive and use machines: Ixekizumab (Taltz) has no or negligible influence on the ability to drive and use machines.

Women of childbearing potential: Women of childbearing potential should use an effective method of contraception during treatment and for at least 10 weeks after treatment.
Pregnancy: There is a limited amount of data from the use of ixekizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or post-natal development (see Pharmacology: Toxicology: Preclinical safety data under Actions). As a precautionary measure, it is preferable to avoid the use of Ixekizumab (Taltz) during pregnancy.
Breastfeeding: It is not known whether ixekizumab is excreted in human milk or absorbed systemically after ingestion. However, ixekizumab is excreted at low levels in the milk of cynomolgus monkeys. A decision should be made whether to discontinue breastfeeding or to discontinue Ixekizumab (Taltz) taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility: The effect of ixekizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: The most frequently reported adverse reactions were injection site reactions (15.5%) and upper respiratory tract infections (16.4%) (most frequently nasopharyngitis).
Tabulated list of adverse reactions: Adverse reactions from clinical studies and postmarketing reports (Table 14) are listed by MedDRA system organ class. Within each system organ class, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).
A total of 8,956 patients have been treated with Ixekizumab (Taltz) in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and other autoimmune conditions. Of these, 6,385 patients were exposed to Ixekizumab (Taltz) for at least one year, cumulatively representing 19,833 patient years of exposure and 196 children cumulatively representing 207 patient years of exposure. (See Table 14.)

Click on icon to see table/diagram/image

Description of selected adverse reactions: Injection site reactions: The most frequent injection site reactions observed were erythema and pain. These reactions were predominantly mild to moderate in severity and did not lead to discontinuation of Ixekizumab (Taltz).
In the adult plaque psoriasis studies, injection site reactions were more common in subjects with a body weight <60 Kg compared with the group with a body weight ≥60 Kg (25% vs. 14% for the combined Q2W and Q4W groups). In the psoriatic arthritis studies, injection site reactions were more common in subjects with a body weight <100 Kg compared with the group with a body weight ≥100 Kg (24% vs. 13% for the combined Q2W and Q4W groups). In the axial spondyloarthritis studies, injection site reactions were similar in subjects with a body weight <100 kg compared with the group with a body weight ≥100 kg (14% vs. 9% for the combined Q2W and Q4W groups). The increased frequency of injection site reactions in the combined Q2W and Q4W groups did not result in an increase in discontinuations in either the plaque psoriasis, the psoriatic arthritis or the axial spondyloarthritis studies.
Infections: In the placebo-controlled period of the phase III clinical studies in plaque psoriasis in adults, infections were reported in 27.2% of patients treated with Ixekizumab (Taltz) for up to 12 weeks compared with 22.9% of patients treated with placebo.
The majority of infections were non-serious and mild to moderate in severity, most of which did not necessitate treatment discontinuation. Serious infections occurred in 13 (0.6%) of patients treated with Ixekizumab (Taltz) and in 3 (0.4%) of patients treated with placebo (see Precautions). Over the entire treatment period infections were reported in 52.8% of patients treated with Taltz (46.9 per 100 patient years). Serious infections were reported in 1.6% of patients treated with Ixekizumab (Taltz) (1.5 per 100 patient years).
Infection rates observed in psoriatic arthritis and axial spondyloarthritis clinical studies were similar to those observed in the plaque psoriasis studies with the exception of the frequencies of the adverse reactions of influenza and conjunctivitis which were common in patients with psoriatic arthritis.
Laboratory assessment of neutropenia and thrombocytopenia: In plaque psoriasis studies, 9% of patients receiving Ixekizumab (Taltz) developed neutropenia. In most cases, the blood neutrophil count was ≥1,000 cells/mm³. Such levels of neutropenia may persist, fluctuate or be transient. 0.1% of patients receiving Ixekizumab (Taltz) developed a neutrophil count <1,000 cells/mm³. In general, neutropenia did not require discontinuation of Ixekizumab (Taltz). 3% of patients exposed to Ixekizumab (Taltz) had a shift from a normal baseline platelet value to <150,000 platelet cells/mm³ to ≥75,000 cells/mm³. Thrombocytopenia may persist, fluctuate or be transient.
The frequency of neutropenia and thrombocytopenia in psoriatic arthritis and axial spondyloarthritis clinical studies is similar to that observed in the plaque psoriasis studies.
Immunogenicity: Approximately 9-17% of adult plaque psoriasis patients treated with Ixekizumab (Taltz) at the recommended dosing regimen developed anti-drug antibodies, the majority of which were low titers and not associated with reduced clinical response up to 60 weeks of treatment. However, approximately 1% of patients treated with Ixekizumab (Taltz) had confirmed neutralizing antibodies associated with low drug concentrations and reduced clinical response.
In psoriatic arthritis patients treated with Ixekizumab (Taltz) at the recommended dosing regimen up to 52 weeks, approximately 11% developed anti-drug antibodies, the majority of which were low titer, and approximately 8% had confirmed neutralizing antibodies. No apparent association between the presence of neutralizing antibodies and impact on drug concentration or efficacy was observed.
In paediatric psoriasis patients treated with Ixekizumab (Taltz) at the recommended dosing regimen up to 12 weeks, 21 patients (18%) developed anti-drug antibodies, approximately half were low titer and 5 patients (4%) had confirmed neutralizing antibodies associated with low drug concentrations. There was no association with clinical response or adverse events.
In radiographic axial spondyloarthritis patients treated with Ixekizumab (Taltz) at the recommended dosing regimen up to 16 weeks, 5.2% developed anti-drug antibodies, the majority of which were low titer, and 1.5% (3 patients) had neutralizing antibodies (NAb). In these 3 patients, NAb-positive samples had low ixekizumab concentrations and none of these patients achieved an ASAS40 response. In non-radiographic axial spondyloarthritis patients treated with Ixekizumab (Taltz) at the recommended dosing regimen for up to 52 weeks, 8.9% developed anti-drug antibodies, all of which were low titer; no patient had neutralizing antibodies; and no apparent association between the presence of anti-drug antibodies and drug concentration, efficacy, or safety was observed.
Across all indications, an association between immunogenicity and treatment emergent adverse events has not been clearly established.
Paediatric population: The safety profile observed in children with plaque psoriasis treated with Ixekizumab (Taltz) every 4 weeks is consistent with the safety profile in adult patients with plaque psoriasis with the exception of the frequencies of conjunctivitis, influenza, and urticaria which were common. Inflammatory bowel disease was also more frequent in paediatric patients, although it was still uncommon. In the paediatric clinical study, Crohn's disease occurred in 0.9% of patients in the Ixekizumab (Taltz) group and 0% of patients in the placebo group during the 12 week, placebo-controlled period. Crohn's disease occurred in a total of 4 Ixekizumab (Taltz) treated subjects (2.0%) during the combined placebo-controlled and maintenance periods of the paediatric clinical study.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

In plaque psoriasis studies, the safety of Ixekizumab (Taltz) in combination with other immunomodulatory agents or phototherapy has not been evaluated.
In population pharmacokinetic analyses, clearance of ixekizumab was not affected by concomitant administration of oral corticosteroids, NSAIDs, sulfasalazine, or methotrexate.
Cytochrome P450 substrates: Results from an interaction study in patients with moderate-to-severe psoriasis determined that 12 weeks of administration of Ixekizumab with substances metabolized by CYP3A4 (i.e., midazolam), CYP2C9 (i.e., warfarin), CYP2C19 (i.e., omeprazole), CYP1A2 (i.e., caffeine) or CYP2D6 (i.e., dextromethorphan) does not have a clinically significant impact on the pharmacokinetics of these substances.

Incompatibilities: Not applicable.
Special precautions for disposal and other handling: The instructions for using the pen, included with the package leaflet, must be followed carefully.
The prefilled pen is for single use only.
Ixekizumab (Taltz) should not be used if particles appear or if the solution is cloudy and/or distinctly brown.
Ixekizumab (Taltz) that has been frozen must not be used.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator (2°C-8°C). Do not freeze. Do not use if frozen. Do not shake. Store in the original package in order to protect from light.
Ixekizumab (Taltz) may be stored unrefrigerated for up to 5 days at a temperature not above 30°C.
Shelf life: 2 years.

Immunosuppressants

L04AC13 - ixekizumab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.

Rx