Treatment Efficacy | Rheumatology AS

More insurance plans than ever are offering Taltz as the Preferred IL-17A antagonist across Commercial and Part D.

Difference between ASAS40 and ASAS20

00:00
[Music begins with title and Lilly logo on screen.]
Caption: Raising the bar with ASAS40

00:05
[Frame transitions to Dr. Lisse with his name and title on the bottom left corner of the screen. Dr. Lisse is speaking to camera. At 00:12, camera zooms out to show more of Dr. Lisse.]
Dialogue: Dr. Jeffrey Lisse: Hello, I'm doctor Jeffrey Lisse. I'm a rheumatologist and a medical fellow with Eli Lilly and I'm here today to talk to you about the ASAS response criteria for patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis.
Caption: Jeffrey R. Lisse, MD

00:23
[Frame transitions to the four domains of patient response. Domains appear as red rounded rectangular quadrants each with a text and an icon. Dr. Lisse continues to speak and discusses the four domains.]
Dialogue: Dr. Jeffrey Lisse: What you see in front of you on this slide has the 4 overall domains that we look at to measure this response. It includes the patient's global assessment, their spinal pain, inflammation, and function. These are the overall problems that most patients will complain of when they come in to the physician's office.
Caption: Domains defined¹, Patient global assessment, Spinal pain, Inflammation, Function

00:47
[Frame transitions to a chart comparing the differences between ASAS20 and ASAS40 response. Dr. Lisse describes the graph information.]
Dialogue: Dr. Jeffrey Lisse: The ASAS20 was originally developed as a measure for non-steroidal anti-inflammatory drug, or NSAID, trials. It's used as a regulatory endpoint however, and many clinical trials have used it as their primary endpoint. In order to reach an ASAS20, patients have to have an improvement of at least 20% and at least one unit on a numerical rating scale in 3 out of the 4 domains that I just mentioned to you. The last domain can get worse but it cannot worsen by more than 20% or 1 unit. The ASAS40 is more stringent. Here the patient requires a 40% improvement and 2 units in 3 of the 4 domains, plus the remaining domain cannot worsen at all. So, the ASAS40 is obviously a higher bar than the ASAS20.
Caption: ASAS40 is a higher bar than ASAS20^1,2 The difference between ASAS20 and ASAS40 is more than a 20% vs 40% improvement, ASAS40 Improvement: ≥40% and ≥2 units in 3 of 4 domains^* + Does NOT allow for any worsening^*, ASAS20 Improvement: ≥20% and ≥1 unit in 3 of 4 domains^* + No worsening of ≥20% and ≥1 unit in the remaining domain^*
^*All 4 domains are based on a rating scale of 0-10.

01:47
[Frame transitions to a graph showing ASAS response criteria. Dr. Lisse describes the graph information.]
Dialogue: Dr. Jeffrey Lisse: To give you an example of how this works in a given patient in a clinical trial, here we've got the 4 domains measured. So this patient came into the clinical trial and their global assessment is at a 7 out of 10, the spinal pain and inflammation are 6 out of 10, and function is again at 7 out of 10.
Caption: ASAS response criteria, Assessment of the 4 ASAS core domains^*, Lilly | CIQ, USCIQ-RES-221-QQQ Accessibility Resource (Version 0), Hypothetical patient example, Score at baseline, 10 9 8 7 6 5 4 3 2 1 0, Patient global assessment, Spinal pain, Inflammation, Function
^*All 4 domains are based on a rating scale of 0-10.

02:06
[Title and content of chart is built upon with more data as Dr. Lisse continues to speak to the graph.]
Dialogue: Dr. Jeffrey Lisse: In order to achieve an ASAS40 for example, here are some of the potential measurements for this patient over time. So here we have the patient's global assessment has not changed. Their spinal pain has improved by 50% or 3 units, as has their inflammation. And their function has improved by 40% or 2 units. So 3 of the domains have gotten 40% better, and at least 2 units better, and the remaining domain has not worsened at all. So this patient's achieved an ASAS40.
Caption: Scoring the higher benchmark: ASAS40, Assessment of the 4 ASAS core domains^*, Hypothetical patient example, Score at baseline, ASAS40 score at week 16, 10 9 8 7 6 5 4 3 2 1 0, ASAS40 Improvement at week 16, Patient global assessment 0% 0 units, Spinal pain 50% 3 units, Inflammation 50% 3 units, Function 40% 2 unit
^*All 4 domains are based on a rating scale of 0-10.

02:38
[Title and content of chart is built upon with more data as Dr. Lisse continues to speak to the graph.]
Dialogue: Dr. Jeffrey Lisse: By comparison, these lighter arrows show you what the patient could look like if they achieved just an ASAS20. So in this case the patient's spinal pain and inflammation got 2 units better at 33%. The patient's function got 1 unit better and 20%. So 3 of the units are 20% better and 1 unit better. The 4th domain however, the global assessment, got worse. It did not worsen up to 20%, so this patient would achieve an ASAS20. Clearly this is not adequate for an ASAS40 in this person.
Caption: Scoring ASAS20 vs ASAS40, Assessment of the 4 ASAS core domains^*, Hypothetical patient examples, Score at baseline, ASAS40 score at week 16, ASAS20 score at week 16, 10 9 8 7 6 5 4 3 2 1 0, ASAS40 Improvement at week 16, Patient global assessment -7% 0.5 units, Spinal pain 33% 2 units, Inflammation 33% 2 units, Function 20% 1 unit
^*All 4 domains are based on a rating scale of 0-10.

03:18
[Frame transitions to two rounded rectangles comparing ASAS20 to ASAS40. Dr. Lisse highlights how ASAS40 can raise the bar for patients.]
Dialogue: Dr. Jeffrey Lisse: The ASAS40 can raise the bar and is most likely a more clinically relevant outcome for patients and physicians.
Caption: ASAS40 can raise the bar for your patients^1,2, ASAS40 is a more stringent endpoint, ASAS40, ASAS20, ASAS20 is a less stringent endpoint

03:28
[Frame transitions back to Dr. Lisse. He is speaking to the camera.]
Dialogue: Dr. Jeffrey Lisse: Thank you.

03:30
[Frame transitions to Lilly logo and references.]
Caption: Lilly

References:

Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001;44:1876-1886.
Brandt J, Listing J, Sieper J, Rudwaleit M, van der Heijde D, Braun J. Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ann Rheum Dis. 2004;63:1438-1444.

FOR BIOLOGIC-NAIVE PATIENTS WITH ANKLYOSING SPONDYLITIS

Rapid improvement in back pain, function, and inflammation seen as early as Week 2 in some patients^4,8

COAST-V IMPROVEMENT IN ASAS COMPONENT SCORES THROUGH WEEK 16, MMRM VS PLACEBO^14,15

LSM change fro baseline over time with different treatments

^*P<0.01 vs placebo. Nominal P value: not controlled for type 1 error; therefore, no statistical comparisons can be made.
^†P<0.001 vs placebo.
^‡Mean of BASDAI questions 5 and 6 (morning stiffness duration and morning stiffness severity).

COAST-V was not designed to test the noninferiority or superiority of Taltz to adalimumab. Thus, these data should not be used to compare the efficacy between these products.

ADDITIONAL WEEK 16 ASAS component results

For Patient’s Global Assessment score, change from baseline in Patient’s Global Assessment score at week 16 was -2.5 (baseline 6.9) for patients receiving Taltz, -2.6 (baseline 7.1) for those receiving adalimumab, and -1.4 (baseline 7.1) for placebo.

For Spinal Pain Assessment score, Function score, and Inflammation score, mean baseline was 7.2, 6.1, and 6.5 for patients receiving Taltz; 7.0, 6.1, and 6.6 for those receiving adalimumab; and 7.4, 6.4, and 6.8 for placebo, respectively.

Patient's Global Assessment score range 0-10.

ADDITIONAL WEEK 16 RESULTS FROM COAST-W TRIAL, MMRM^1,3

Among TNFi-experienced patients, change from baseline in inflammation at week 16 was -2.42 (baseline 7.21) for patients receiving Taltz and -0.70 (baseline 7.20) for placebo, and change from baseline in BASFI at week 16 was -1.69 (baseline 7.35) for patients receiving Taltz and -0.64 (baseline 7.01) for placebo, and change from baseline in spinal pain at week 16 was -2.4 (baseline 7.9) for patients receiving Taltz and -1.0 (baseline 7.8) for placebo, and change from baseline in Patient’s Global Assessment score at week 16 was -2.4 (baseline 8.0) for patients receiving Taltz, and -0.7 (baseline 7.8) for placebo.

Primary endpoint=ASAS40 at week 16 (see data below).

Click here for COAST-V and -W trial designs

SELECT IMPORTANT SAFETY INFORMATION
INFLAMMATORY BOWEL DISEASE
Patients treated with Taltz may be at an increased risk of inflammatory bowel disease. In clinical trials, Chron’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the Taltz group that the placebo group, During Taltz treatment, monitor patients for onset or exacerbation of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

Rapid ASAS40 response seen as early as Week 2 in some patients that is sustained through week 52^4,16-8

COAST-V (BIOLOGIC-NAIVE): ASAS40 response rates through week 52, NRI

COAST-V ASAS40 respsonse rates through 52 weeks chart

^*Nominal P value: Taltz P=.003, Humira P=.001 vs placebo. Not controlled for type-I error; therefore, no statistical conclusions can be made. Results at week 2: Taltz=20%; Humira=21%; placebo=5%.
^†P<.0001 vs placebo at week 16.
^‡P=.0053 vs placebo at week 16.
Primary endpoint=ASAS40 at week 16.
NRI of ITT population through weeks 16 and 52.

COAST-V was not designed to test the noninferiority or superiority of Taltz to Humira. Thus, these data should not be used to compare the efficacy between these products.

The extended treatment period of the study (weeks 16-52) has limitations (i.e., no placebo comparison, patients remaining in the extension phase may be those more responsive to treatment).

Additional week 16 and 52 results from COAST-W trial^4,19,20

In COAST-W (TNFi-experienced) (Taltz 80 mg every 4 weeks n=114; placebo n=104), 25% of patients receiving Taltz achieved ASAS40 at week 16 vs 13% of patients receiving placebo. At week 52, 34% of patients receiving Taltz achieved ASAS40.

Click here for COAST-V and -W trial designs

SELECT IMPORTANT SAFETY INFORMATION
IMMUNIZATIONS
Prior to initiating Taltz, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avid use of live vaccines inpatients treated with Taltz.

References:

Data on file. Lilly USA, LLC. DOF-IX-US-0304.
Mease P, van der Heidje D, Ritchlin CT, et al; on behalf of SPIRIT-P1 Study Group. 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. Ann Rheum Dis. 2017;76:79-87.
Nash P, Kirkham B, Okada M, et al; on behalf of SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase III trial. Lancet. 2017;389:2317-2327.
Taltz. Prescribing Information. Lilly USA, LLC.
Data on file. Lilly USA, LLC. DOF-IX-US-0013.
Chandran V, van der Heijde D, Fleischmann RM, et al. Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1). Rheumatology. 2020;59:2774-2784.
Data on file. Lilly USA, LLC. DOF-IX-US-0247.
Data on file. Lilly USA, LLC. DOF-IX-US-0308.
Nash P, Kirkham B, Okada M, et al; on behalf of SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase III trial. Lancet. 2017;389:2317-2327. Supplementary appendix.
Data on file. Lilly USA, LLC. DOF-IX-US-0102.
Data on file. Lilly USA, LLC. DOF-IX-US-0012.
Data on file. Lilly USA, LLC. DOF-IX-US-0278.
Orbai A, Gratacós J, Turkiewicz A, et al. Efficacy and Safety of Ixekizumab in Patients with Psoriatic Arthritis and Inadequate Response to TNF Inhibitors: 3-Year Follow-Up (SPIRIT-P2). Rheumatol Ther. 2021;8:199-217. https://doi.org/10.1007/s40744-020-00261-0.
Data on file. Lilly USA, LLC. DOF-IX-US-0158.
Data on file. Lilly USA, LLC. DOF-IX-US-0163.
Van der Heijde D, Cheng-Chung Wei J, Dougados M, et al; COAST-V Study Group. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondyloarthritis…
Data on file. Lilly USA, LLC. DOF-IX-US-0155.
Data on file. Lilly USA, LLC. DOF-IX-US-0157.
Deodhar A, Possubnyy D, Pacheco-Tena C, et al; COAST-W Study Group. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. Arthritis Rheumatol. 2019;71:599-611.
Data on file. Lilly USA, LLC. DOF-IX-US-0162.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

Taltz is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.

WARNINGS AND PRECAUTIONS:

Infections
Taltz may increase the risk of infection. In clinical trials of adult patients with plaque psoriasis, the Taltz group had a higher rate of infections than the placebo group (27% vs 23%). A similar increase in risk of infection was seen in placebo-controlled trials of adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis. Serious infections have occurred. Instruct patient s to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue Taltz until the infect ion resolves.

Pre-Treatment Evaluation for Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with Taltz. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering Taltz. Closely monitor patients receiving Taltz for signs and symptoms of active TB during and after treatment.

Hypersensitivity
Serious hypersensitivity reactions, including angioedema and urticaria (each ≤ 0.1%). occurred in the Taltz group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post marketing use with Taltz. If a serious hypersensitivity reaction occurs, discontinue Taltz immediately and initiate appropriate therapy.

Inflammatory Bowel Disease
Patients treated with Taltz may be at an increased risk of inflammatory bowel disease. In clinical trials, Crohn's disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the Taltz group than the placebo group. During Taltz treatment, monitor patients for onset or exacerbations of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

Immunizations
Prior to initiating therapy with Taltz, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with Taltz.

ADVERSE REACTIONS

Most common adverse reactions (≥1%) associated with Taltz treatment are injection site reactions, upper respiratory tract infections, nausea, and tinea infections. Overall, the safety profiles observed in adult patients with psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and pediatric patients with plaque psoriasis were consistent with the safety profile in adult patients with plaque psoriasis, with the exception of influenza and conjunctivitis in psoriatic arthritis and conjunctivitis, influenza, and urticaria in pediatric psoriasis.

Please see Prescribing Information and Medication Guide. Please see Instructions for Use included with the device.

IX HCP ISI 07MAY2020

INDICATIONS

Taltz is indicated for adults with active psoriatic arthritis (PsA), for adults with active ankylosing spondylitis (AS), and for adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation. Taltz is also indicated for patients aged 6 years or older with moderate-to-severe plaque psoriasis (PsO) who are candidates for systemic therapy or phototherapy.

Taltz is for Today and Tomorrow