Psoriatic Arthritis Efficacy

ACR results

Powerful joint symptom results in both biologic-naive and TNFi-experienced patients^1-3

^*P≤.001 vs placebo; ^†P <.0001 vs placebo.

Primary endpoint=ACR20 response at week 24.

Inadequate responders (<20% improvement in tender and in swollen joint counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint. Nonresponders imputation (NRI) of intent-to-treat population through week 24.

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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 patients 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 infection resolves.

Radiographic response

Results at week 16

FOR BIOLOGIC NAIVE PATIENTS WITH PSORIATIC ARTHRITIS

Taltz helped stop the progression of structural joint damage at week 16 vs placebo^1-3,7

Primary endpoint=ACR20 response at week 24.

Inhibition of progression of structural damage was assessed radiographically and expressed as the mean change in mTSS and its components, the joint space narrowing score and bone erosion score, at week 16 vs baseline. The mTSS score was modified for psoriatic arthritis by addition of hand distal interphalangeal (DIP) joints.

SPIRIT-P2 (TNFi-experienced) did not include an assessment of radiographic progression.

mTSS=modified Total Sharp Score; MMRM=mixed-effect model of repeated measure.

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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 exacerbation of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

Results at week 52

89% of Taltz patients had almost no progression of structural joint damage^* at week 52^8,9

^*Defined as ≤.5 change from baseline.

^†n=total number of patients in the extension period population.

^‡Nx=number of non-missing changes from baseline in mTSS at week 52.

Patient and site personnel were blinded to study treatment until all patients completed week 24 or discontinued. The open table extension phase of the study has limitations (eg, no placebo comparison, patients remaining in the extension phase many be those with better results).

Patients in the extension period population were all patients administered Taltz on or after Week 24.

The data presented were from post hoc analyses and were not placebo-controlled.

Mean change from baseline in mTSS at week 52 was 0.47 for patients in the extension period on Taltz 80 mg every 4 weeks.

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

Dactylitis

Results at week 24

Taltz showed improvement in patients with preexisting dactylitis^2,3,10

Mean baseline LDI-B was 73.0 for Taltz and 62.7 for placebo.

In SPIRIT-P2 (TNFi-experienced) (Taltz 80 mg every 4 weeks n=28, mean baseline=31.5; placebo n=14, mean baseline=37.3), 75% of Taltz patients had complete resolution of dactylitis at week 24 vs 21% for placebo.

The data presented were from post hoc analyses and were not type-I error-controlled; therefore, treatment differences between Taltz and placebo cannot be regarded as statistically significant.

Inadequate responders (<20% in tender and in swollen join counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

LDI-B=Leads Dactylitis Index-Basic.

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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.

Results at week 156

FOR BIOLOGIC-NAIVE PATIENTS WITH PSORIATIC ARTHRITIS

Complete resolution of dactylitis (LDI-B=0) through year 3

Double-blind and open-label extension periods, ITT population

Patients with dactylitis (LDI-B>0) at baseline
Mean baseline score-73

Primary endpoint=ACR20 response at week 24.

In an mNRI analysis of patients receiving Taltz, 83% of patients achieved LDI-B=0 at week 52, 77% at week 108, and 62% at week 156. mNRI of intent-to-treat (ITT) population through week 156.

mNRI, a preferred method for analyzing long term efficacy, imputes missing data due to study drug (e.g., inadequate response, adverse event, or lack of efficacy), as nonresponse; whereas, missing data due to other reasons (e.g., missed visits, lost to follow-up) is included as a predicted value based on statistical modeling of observed data.

Inadequate responders (<20% improvement in tender and in swollen joint counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

After week 24, patients knew they were taking active treatment, but remained blind to the dose until the last patient completed week 24. The uncontrolled extension period of the study has limitations (e.g., no placebo comparisons, patients remaining in the study may be those with better results).

LDI-B=Leeds Dactylitis Index-Basic.

mNRI=modified nonresponder imputation.

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

Enthesitis

Results at week 24

Taltz showed improvement in patients with preexisting enthesitis^2,3,10,12

Mean baseline LEI was 2.8 for Taltz and 2.9 for placebo.

In SPIRIT-P2 (TNFi-experienced) in patients with LEI >0 (Taltz 80 mg every 4 weeks n=68, mean baseline=2.9; placebo n=69, mean baseline=2.9), LEI=0 at week 24, a prespecified, error-controlled endpoint, was not statistically significant vs placebo. At week 24, 35% of Taltz patients had LEI=0 vs 22% for placebo.

The data presented from SPIRIT-P1 were from post hoc analyses and were not type-I error-controlled; therefore, treatment differences between Taltz and placebo cannot be regarded as statistically significant. In addition, the mean change from baseline in LEI score at week 12 (prespecified endpoint in SPIRIT-P1) was error-controlled, but was not statistically significant compared to placebo.

Inadequate responders (<20% in tender and in swollen join counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

LEI=Leeds Enthesitis Index.

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SELECT IMPORTANT SAFETY INFORMATION
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 patients 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 infection resolves.

Results at week 156

Complete resolution of enthesitis (LEI=0) through year 3

Double-blind and open-label extension periods, ITT population

Patients with Enthesitis (LEI Score>0) at Baseline
Mean baseline score=2.8

In a modified nonresponder imputation (mNRI) analysis of patients receiving Taltz, 57% of patients achieved LEI=0 at week 52 and 55% at week 108, and 47% at week 156. mNRI of intent-to-treat (ITT) population through week 156.

mNRI, a preferred method for analyzing long term efficacy, imputes missing data due to study drug (e.g., inadequate response, adverse event, or lack of efficacy), as nonresponse; whereas, missing data due to other reasons (e.g., missed visits, lost to follow-up) is included as a predicted value based on statistical modeling of observed data.

Primary endpoint=ACR20 response at week 24.

Inadequate responders (<20% improvement in tender and in swollen joint counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

After week 24, patients knew they were taking active treatment, but remained blind to the dose until the last patient completed week 24. The uncontrolled extension period of the study has limitations (e.g., no placebo comparisons, patients remaining in the study may be those with better results).

LEI=Leeds Enthesitis Index.

mNRI=modified nonresponder imputation.

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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.

Concomitant MTX use

ACR20 response vs placebo with or without concomitant methotrexate^1,14-15

ADDITIONAL WEEK 24 RESULTS FROM SPIRIT-P2 TRIAL

In SPIRIT-P2 (TNFi-experienced) (Taltz 80 mg every 4 weeks n=48; placebo n=40), 50% of Taltz patients achieved ACR20 with concomitant MTX at week 24 vs 18% for placebo. Additionally (Taltz n=74; placebo n=78), 55% of Taltz patients achieved ACR20 without MTX use at week 24 vs 21% for placebo. All patients in SPIRIT-P2 were previously treated with at least 1 cDMARD (methotrexate, sulfasalazine, leflunomide, or hydroxychloroquine)

All patients were allowed to remain on stable background therapy.

Nonresponder imputation (NRI) of intent-to-treat population through week 24.

Inadequate responders (<20% improvement in tender and in swollen joint counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

The data presented were from post hoc analyses and were not type-1 error-controlled; therefore, treatment differences between Taltz and placebo cannot be regarded as statistically significant.

No routine lab monitoring (including liver function tests) is required for treatment with Taltz as monotherapy.

During Taltz treatment, monitor patients for signs and symptoms of infection and for onset or exacerbation of inflammatory bowel disease. During and after treatment with Taltz, monitor patients for active tuberculosis (TB) infection.

MTX=methotrexate.

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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.

Psoriatic Arthritis skin data

Results at week 12

Treatment with Taltz resulted in an improvement in psoriatic skin lesions^1-3,16

In SPIRIT-P1, among patients with sPGA ≥3 at baseline (Taltz 80 mg every 4 weeks n=52; placebo n=41), 75% of patients taking Taltz achieved sPGA 0,1 at week 12 vs 7% who received placebo. Additionally, 31% of patients receiving Taltz achieved sPGA 0 at week 12 vs 2% for placebo.

ADDITIONAL WEEK 12 RESULTS FROM SPIRIT-P2 TRIAL

In SPIRIT-P2 (TNFi-experienced, ≥3% BSA) (Taltz 80 mg every 4 weeks n=68, placebo n=67), 57% of patients receiving Taltz achieved PASI 75 at week 12 vs 10% for placebo. Additionally, 38% and 19% of patients receiving Taltz achieved PASI 90 and PASI 100, respectively, at week 12 vs 6% and 6% for placebo. Among patients with sPGA ≥3 at baseline (Taltz 80 mg every 4 weeks n=60, placebo n=55), 63% of patients taking Taltz achieved sPGA 0,1 at week 12 vs 4% of patients who received placebo. Additionally, 23% of patients receiving Taltz achieved sPGA 0 vs 2% for placebo.

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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 exacerbation of inflammatory bowel disease and if IBD occurs, discontinue Taltz and initiate appropriate medical management.

Results at week 156

Taltz maintained response in skin clearance through year 3^1,17

In an mNRI analysis of patients receiving Taltz, PASI 75 results were 80% at week 52, 69% at week 108, and 64% at week 156. PASI 90 results were 67% at week 52, 61% at week 108, and 51% at week 156. PASI 100 results were 56% at week 52, 47% at week 108, and 44% at week 156.

mNRI analysis imputes missing data due to study drug (e.g., inadequate response, adverse event, or lack of efficacy) as nonresponse; whereas missing data due to other reasons (e.g., missed visits, lost to follow-up) is included as a predicted value based on statistical modeling of observed data.

Inadequate responders (<20% improvement in tender and in swollen joint counts) at week 16 were analyzed as nonresponders after week 16 until the primary endpoint.

After week 24, patients knew they were taking active treatment, but remained blind to the dose until the last patient completed week 24. The uncontrolled extension period of the study has limitations (e.g., no placebo comparisons, patients remaining in the study may be those with better results).

BSA=body surface area; mNRI=modified nonresponder imputation; PASI=Psoriasis Area and Severity Index.

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

References: 1. Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020. 2. 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 3 trial. Lancet. 2017;389:2317-2327. 3. Mease PJ, van der Heijde 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. 4. Data on file. Lilly USA, LLC. DOF-IX-US-0013. 5. Data on file. Lilly USA, LLC. DOF-IX-US-0015. 6. Genovese MC, Combe B, Kremer J, et al. Safety and efficacy of ixekizumab in patients with PsA and previous inadequate response to TNF inhibitors: week 52 results from SPIRIT-P2. Rheumatology. 2018. doi:10.1093/rheumatology/key182. 7. Data on file. Lilly USA, LLC. TAL20171026B. 8. Data on file. Lilly USA, LLC. DOF-IX-US-0017. 9. van der Heijde D, Gladman DD, Kishimoto M, et al. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: 52-week results from a phase III study (SPIRIT-P1). J Rheumatol. 2018;45:367-377. 10. 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 3 trial. Lancet. 2017;389:2317-2327. Supplementary appendix. 11. Data on file. Lilly USA, LLC. TAL04022018A. 12. Data on file. Lilly USA, LLC. TAL20171002A. 13. Data on file. Lilly USA, LLC. TAL04022018B. 14. Data on file. Lilly USA, LLC. TAL20170919A. 15. Data on file. Lilly USA, LLC. TAL20171026A. 16. Data on file. Lilly USA, LLC. TAL20171127A. 17. Data on file. Lilly USA, LLC. DOF-IX-US-0012.