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Efficacy: Evidence of clinical effectiveness

Common treatments may not control the underlying cause or symptoms of nr-axSpA.60-62

For patients with active disease, despite treatment with NSAIDs and physical therapy, the ACR/SAA/SPARTAN Treatment Guidelines strongly recommend TNFi as the first-line biologic therapy.61*

*Recommendations are from the ACR/SAA/SPARTAN 2019 guidelines. Recommendations for nr-axSpA extrapolated from evidence in AS due to limited literature available for nr-axSpA.

C-axSpAnd:

A landmark study in patients with nr-axSpA

Designed by UCB with guidance from the FDA to address questions about the natural history of disease

FDA requisites11,48,63

UCB nr-axSpA trial design1,64

Clearly identify patients with nr-axSpA

Patients had objective signs of inflammation and a central X-ray/MRI reading

Assess long-term treatment effect and potential occurrence of spontaneous remission

A 52-week, placebo-controlled Phase 3 study

Include adequate representation of patients with various types of signs of inflammation

Patient subpopulations: MRI+/CRP+, MRI+/
CRP-, MRI-/CRP+

Optimize background treatment

Allow NBBM and dose adjustments

C-axSpAnd study design

C-axSpAnd: A 52-week, Phase 3, multicenter, randomized, double-blind, placebo-controlled study in patients with nr-axSpA1,64

The study included 317 subjects ≥18 years of age with adult-onset active axial spondyloarthritis for at least 12 months, but without definitive radiographic evidence of structural damage to sacroiliac joints1,64

ACR: American College of Rheumatology; AS: ankylosing spondylitis; CRP: C-reactive protein; MRI: magnetic resonance imaging; NBBM: non-biologic background medication; nr-axSpA: non-radiographic axial spondyloarthritis; NSAID: nonsteroidal anti-inflammatory drug; SAA: Spondylitis Association of America; SPARTAN: The Spondyloarthritis Research and Treatment Network; TNFi: tumor necrosis factor inhibitor.

 

C-axSpAnd study design

*NBBMs include NSAIDs, SAARDs, corticosteroids, and opioids.64
ASAS: Assessment in SpondyloArthritis international Society; ASDAS-MI: Ankylosing Spondylitis Disease Activity Score-Major Improvement; ASQoL: ankylosing spondylitis quality of life; AU: anterior uveitis; BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; CRP: C-reactive protein; LD: loading dose; MRI: magnetic resonance imaging; NBBM: non-biologic background medication; NSAID: nonsteroidal anti-inflammatory drug; OL: open label; Q2W: every 2 weeks; SIJ-SPARCC: sacroiliac joint Spondyloarthritis Research Consortium of Canada; TNF: tumor necrosis factor; ULN: upper limit of normal.

 

C-axSpAnd study subgroups of nr-axSpA patients

The C-axSpAnd study included subgroups of nr-axSpA patients with different MRI and CRP statuses

ASAS: Assessment in SpondyloArthritis international Society; CRP: C-reactive protein; HLA-B27+: human leukocyte antigen B27 positive;
MRI: magnetic resonance imaging; NBBM: non-biologic background medication; Q2W: every 2 weeks.

 

ASDAS disease activity category distribution

ASDAS disease activity category distribution of CIMZIA + NBBM patients (FAS, OC)5,64-66*

ASDAS disease activity category distribution

ASDAS disease activity category distribution of CIMZIA + NBBM patients (FAS, OC)5,64-66*

Comparison of the distribution of the CIMZIA-treated patients by ASDAS disease activity category at baseline vs. 52 weeks for patients who remained in the double-blind study, using observed case analysis.

*Includes patients who continued on CIMZIA for the full year, in addition to optimized NBBM.64

ASDAS: Ankylosing Spondylitis Disease Activity Score; FAS: full analysis set; NBBM: non-biologic background medication;
OC: observed case.

 

ASDAS-Major Improvement responders

CIMZIA-treated patients experienced early improvement in disease activity with greater improvement at Week 521

ASDAS-Major Improvement responders (FAS, NRI)1,5*

 

  • Utilization and dose adjustment of non-biologic background medication (NBBM) (including NSAIDs, SAARDs, corticosteroids, and opioids) were permitted at any time1
  • ASDAS is a validated, highly discriminatory composite index to assess patient disease activity in axSpA through objective evidence of systemic inflammation and patient-reported outcomes

*ASDAS-MI defined as a change from baseline of ≥2.0 in the ASDAS and/or reaching the lowest possible ASDAS value. The same patients may not have responded at each time point.5

ASDAS: Ankylosing Spondylitis Disease Activity Score; FAS: full analysis set; NBBM: non-biologic background medication; NRI: nonresponder imputation; NSAID: nonsteroidal anti-inflammatory drug; Q2W: every 2 weeks; SAARD: slow-acting anti-rheumatic drug.

 

ASAS40 responders

CIMZIA demonstrated rapid and durable improvements in
disease activity in patients with nr-axSpA

ASAS40 responders (FAS, NRI)1,5*

 

  • ASAS criteria measure improvements in pain, function, morning stiffness, and patients’ overall assessment of disease activity. ASAS40 is an improvement of ≥40% and ≥2 units in three domains on a scale of 10.5

*The same patients may not have responded at all time points.
ASAS: Assessment in SpondyloArthritis international Society; FAS: full analysis set; NBBM: non-biologic background medication; NRI: nonresponder imputation; Q2W: every 2 weeks.

 

Total spinal pain and nocturnal spinal pain

CIMZIA reduced spinal pain and inflammation
in patients with nr-axSpA1,5

 

  • Baseline mean total spine score (NRS) was 7.0 for CIMZIA + NBBM patients and 6.9 for placebo + NBBM patients1

 

 

 

 

*Efficacy variables not included in hierarchy or adjusted for multiplicity; therefore, P values were considered nominal.

Nominal P value.

FAS: full analysis set; MCID: minimal clinically important difference; NBBM: non-biologic background medication; nr-axSpA: non-radiographic axial spondyloarthritis; NRS: numerical rating scale; OC: observed case.

 

CRP

CRP

CRP (FAS, OC)5*

 

  • Baseline CRP was 15.79 mg/L for CIMZIA + NBBM patients and 15.84 mg/L for placebo + NBBM patients5
  • The upper limit of normal for CRP was defined as 10 mg/L65

 

 

 

 

 

*Efficacy variables not included in hierarchy or adjusted for multiplicity; therefore, P values were considered nominal.

CRP: C-reactive protein; FAS: full analysis set; NBBM: non-biologic background medication; OC: observed case.

 

Disease activity, physical disability, and enthesitis

CIMZIA reduced disease activity, physical disability, and
enthesitis by over 40% at Week 12 in patients with nr-axSpA5

Disease activity1

Study: C-axSpAnd

Significant BASDAI reduction at Week 12 (FAS, reference-based multiple imputation)5*

Physical disability1

Study: C-axSpAnd

Significant BASFI reduction at Week 12 (FAS, reference-based multiple imputation)5

Enthesitis65

Study: C-axSpAnd

Enthesitis (MASES) reduction at Week 12 (FAS, LOCF)5†

*BASDAI is composed of patient-reported outcomes.

In patients with a baseline MASES score >0. Nominal P value; efficacy variable not in hierarchy, not adjusted for multiplicity.65

Percentage change from baseline.

§P<0.001.

IINominal P value.

BASDAI: Bath Ankylosing Spondylitis Disease Activity Index; BASFI: Bath Ankylosing Spondylitis Functional Index; FAS: full analysis set; LOCF: last observation carried forward; MASES: Maastricht Ankylosing Spondylitis Enthesitis Score; NBBM: non-biologic background medication; nr-axSpA: non-radiographic axial spondyloarthritis.