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a) In the C-OPTIMISE study, the primary endpoint was met. The primary endpoint was remaining flare-free during the double-blind period. A statistically significant proportion of patients who continued on, either a full or reduced CIMZIA^® maintenance dose, remained flare-free during the double-blind period between week 48 and 96, 83.7% (87/104), and 79.0% (83/105), respectively vs. patients who had CIMZIA^® treatment withdrawn (placebo), 20.2% (21/104), p<0.001 vs. placebo in both groups. In terms of the safety profile results, during the maintenance period (weeks 48 to 96), treatment-emergent adverse events were reported in 57.7% (60/104), 61.0% (64/104), and 54.4% (56/104) of patients randomised to CIMZIA^® 200 mg Q2W, CIMZIA^® 200 mg Q4W, or placebo, respectively.⁵

b) In the RAPID-axSpA study, the primary endpoint was met. The primary endpoint was ASAS20 at week 12. ASAS20 response rates were significantly higher at week 12 for CIMZIA^® 200 mg Q2W (n=111) and CIMZIA^® 400 mg Q4W (n=107) arms vs. placebo (n=107) (57.7% and 63.6%, respectively, vs. 38.3%), p≤0.004. In terms of the safety profile results during the 24-week double-blind period, treatment-emergent adverse events were similar between all CIMZIA^® and placebo groups, mostly mild with 58.6% (65/111) for CIMZIA^® 200 mg Q2W, and 59.8% (64/107) for CIMZIA^® 400 mg Q4W, vs. 48.6% (52/107 for placebo), to moderate, 41.4% (46/111) for CIMZIA^® 200 mg Q2W and 40.2% (43/107) for CIMZIA® 400 mg Q4W, vs. 33.6% (36/107 for placebo) in severity. Treatment-emergent adverse events were generally considered by the investigator as unrelated to study medication.¹⁵

c) In the C-VIEW study, the primary endpoint was met. The primary endpoint was the acute anterior uveitis flare event rate during 96 weeks’ CIMZIA^® treatment vs. 2 years pre-baseline. In C-VIEW, there was a statistically significantly lower poisson-adjusted event rate per 96 weeks in the 96-week treatment-period with CIMZIA® 200 mg Q2W, compared to 2 years pre-baseline (0.3 and 1.9, respectively), p<0.001 (n=89). In terms of the safety profile results, 80.9% (72/89) of patients in the safety set experienced an adverse event during the study; excluding cases of uveitis, iridocyclitis and iritis, 73.0% (65/89) of patients experienced an adverse event.16o

d) In the RAPID-PsA study, the clinical primary endpoint at week 12 was met. The primary endpoint at week 12 was ACR20 response. ACR20 responses at week 12 were significantly greater for CIMZIA® 200 mg Q2W (n=138) and 400 mg Q4W-treated (n=135) patients vs. placebo, 58.0% and 51.9% vs. 24.3%, respectively (p<0.001). Rates of adverse events, serious adverse events, and infections were similar between treatment groups. In terms of safety profile results during the 24-week double-blind period, 68.1% (94/138) of patients who received CIMZIA® 200 mg Q2W, 71.1% (96/135) of patients who received CIMZIA® Q4W, and 67.6% (92/136) of patients who received placebo experienced an adverse event.¹⁷

e) In the RAPID 1 study, both co-primary endpoints were met. The co-primary end points were ACR20 response at week 24 and mean change from baseline in modified total Sharp score at week 52. Firstly, ACR20 response rates at week 24 using nonresponder imputation for the CIMZIA® 200 mg (n=393) and CIMZIA® 400 mg (n=390) groups were 58.8% and 60.8%, respectively, vs. 13.6% for the placebo group (n=199), p<0.001 vs. placebo. Secondly, mean radiographic progression from baseline to week 52 was reduced in patients treated with CIMZIA® 200 mg (n=393) by 0.4 Sharp units and CIMZIA® 400 mg (n=390) by 0.2 Sharp units vs. 2.8 Sharp units by placebo (n=199), (p<0.001 by rank analysis). In terms of the safety profile results, since the mean exposure to study treatment was markedly longer in the two CIMZIA® groups than in the placebo group, adverse events were analysed as the number of patients experiencing an event per 100 patient-years or as the incidence rate per 100 patient-years. The overall rates of treatment-emergent adverse events were 125.9 per 100 patient-years in the placebo group, and 96.6 per 100 patient-years and 94.6 per 100 patient-years in the CIMZIA® 200 mg and 400 mg groups, respectively (treatment-adverse events were reported if they occurred after the first administration of CIMZIA® and up to 12 weeks after administration of the last dose.¹⁸

f) In the FAST4WARD study, the primary endpoint was met. The primary endpoint was ACR20 response at week 24. In FAST4WARD, there were greater ACR20 response rates at week 24, with 45.5% for CIMZIA® 400 mg (n=111) vs. 9.3% for placebo (n=109) (p<0.001). In terms of the safety profile results, treatment-emergent adverse events took place in 75.7% (84/111) of patients who received CIMZIA® 400 mg, and 57.8% (63/109) of patients who received placebo.19

g) In the study 014 study, the primary endpoint was met. The primary endpoint was ACR20 response at week 24. In the study 014 study, there were greater ACR20 response rates with 45.9% for CIMZIA® (n=124), vs. 22.9% for placebo (n=119), (p<0.001). In terms of the safety profile results, 78.2% (97/124) patients experienced an adverse event with CIMZIA® 400 mg, vs. 69.7% (83/119) with placebo.²⁰

h) In the CIMPASI-1 and CIMPASI-2 studies, both co-primary endpoints were met. The co-primary endpoints were week 16 responder rates, defined as PASI75 response, and PGA 0/1 and ≥2-point improvement. Firstly, significantly higher PASI75 responder rates at week 16 were observed for CIMZIA®: in CIMPASI-1, 75.8% for CIMZIA® 400 mg (n=88) and 66.5% for CIMZIA® 200 mg (n=95), vs. 6.5% for placebo (n=51), (p<0.0001 for both); in CIMPASI-2, 82.6% for CIMZIA® 400 mg (n=87) and 81.4% for CIMZIA® 200 mg (n=91), vs. 11.6% for placebo (n=49), (p<0.0001 for both). Secondly, significantly higher PGA 0/1 responder rates at week 16 were observed for CIMZIA®: in CIMPASI-1, 57.9% for CIMZIA® 400 mg (n=88) and 47.0% for CIMZIA® 200 mg (n=95), vs. 4.2% for placebo (n=51), (p<0.0001 for both); in CIMPASI-2, 71.6% for CIMZIA® 400 mg (n=87) and 66.8% for CIMZIA® 200 mg (n=91), vs. 2.0% for placebo (n=49), (p<0.0001 for both). In terms of the safety profile results from baseline to week 16 in CIMPASI-1, 54.7% (52/95) patients experienced an adverse event with CIMZIA® 200 mg and 64.8% (57/88) with CIMZIA® 400 mg, vs. 54.9% (28/51)­ with placebo. From baseline to week 16 in CIMPASI-2, 60.0% (54/90) of patients experienced an adverse event with CIMZIA® 200 mg and 69.0% (60/87) with CIMZIA® 400 mg, vs. 67.3% (33/49)­ with placebo.²¹

i) In the CIMPACT study, the primary endpoint at week 12 was met. The primary endpoint was PASI75 response at week 12. PASI75 responder rates were significantly greater for patients who received CIMZIA® 400 mg (n=167) at 66.7% and CIMZIA® 200 mg (n=165) at 61.3%, vs. 5% for patients who received placebo (n=57), (p<0.0001 vs. placebo for both). In terms of the safety profile results from baseline to week 12, treatment-emergent adverse events were reported in 49.1% (82/167) of patients who received CIMZIA® 400 mg, 47.3% (78/165) of patients who received CIMZIA® 200 mg, and 56.1% (32/57) of patients who received placebo.²²

j) Including the five appendicitis events confirmed as SIEs during the previous safety update in RA.²³

k) Before 2007, a positive TB result on the PPD tuberculin skin test varied (from ≥5 to ≥20 mm) according to geographic region. Since 2007, CIMZIA® recommendations internationally mandate all patients with PPD ≥5 mm receive treatment for latent TB infection. There were no patients with axSpA or PsA enrolled prior to 2007.23

l) Lymphoma cases include two cases of Hodgkin’s disease, one in RA and one in PSO.²³

m) Worsening psoriasis defined as psoriasis reported as an AE in a patient enrolled in a PSO study; new-onset psoriasis defined as psoriasis in a patient enrolled in a non-PSO study.²³

n) Includes serious and non-serious deep vein thrombosis and pulmonary embolism events.²³

o) CIMZIA® is not registered for the treatment of uveitis.¹

ACR: American College of Rheumatology; AE: Adverse event; ASAS: Assessment of SpondyloArthritis International Society; ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: Axial spondyloarthritis; DMARD: Disease-modifying anti-rheumatic drug; mTSS: Modified total Sharp score; MTX: Methotrexate; NMSC: Non-melanoma skin cancer; OLE: Open-label extension; PASI: Psoriasis area and severity index; PGA: Physician's global assessment; PPD: Purified protein derivative; PsA: Psoriatic arthritis; PSO: Plaque psoriasis; PY: Patient year; RCT: Randomised controlled trial; RA: Rheumatoid arthritis; SIE: Serious infectious event; TB: Tuberculosis; Q2W: Every two weeks; Q4W: Every four weeks.

C-OPTIMISE: A phase 3b trial in 736 adult patients living with early active axSpA who received open-label CIMIZIA® 200 mg Q2W in a 48-week induction phase (after a loading dose period, where patients received CIMZIA® 400 mg at week 0, week 2, and week 4) before being randomised to receive a maintenance dose in a 48-week placebo-controlled period if they had achieved sustained remission (sustained remission was defined as ASDAS inactive disease (ASDAS-ID: ASDAS <1.3) at week 32 or week 36, and at week 48 (with ASDAS <2.1 for week 32 and week 36)). The primary endpoint was the percentage of patients remaining flare-free during the maintenance period (a flare was defined as ASDAS ≥2.1 (high disease activity) at two consecutive visits, or ASDAS >3.5 (very high disease activity) at any visit).⁵

RAPID-axSpA: A phase 3 trial in 325 adult patients living with active axSpA who were randomised 1:1:1 to receive placebo, or, CIMZIA® 400 mg at week 0, week 2, and week 4 (loading dose) followed by either CIMZIA® 200 mg Q2W or CIMZIA® 400 mg Q4W for the remainder of the 24-week double-blind period, followed by a dose-blind period where patients received CIMZIA® 200 mg Q2W or CIMZIA® 400 mg from week 24 to week 48, followed by an open-label period from week 48 to week 204. The primary endpoint was ASAS20 at week 12.¹⁵

C-VIEW: A 104-week phase 4 study in 89 adult patients living with active axSpA who received CIMZIA® 200 mg Q2W (after a loading dose period). The primary endpoint was the acute anterior uveitis flare event rate during 96 weeks’ CIMZIA® treatment vs. 2 years pre-baseline.16
RAPID-PSA: A 24-week phase 3 trial in 409 adult patients living with active PsA who may have previously received an anti-TNF and were randomised 1:1:1 to receive placebo, or, CIMZIA® 400 mg at week 0, week 2, and week 4 (loading dose) followed by either CIMZIA® 200 mg Q2W or CIMZIA® 400 mg Q4W. The primary endpoints were ACR20 at week 12 and change in mTSS at week 24 vs. baseline.¹⁷
RAPID 1: A 52-week phase 3 trial in 982 adult patients living with active RA who were randomised 2:2:1 to receive CIMZIA® 200 mg Q2W plus MTX (after a loading dose period), or CIMZIA® 400 mg Q2W (after a loading dose period), or placebo plus MTX. Primary endpoints were ACR20 at week 24 and change in mTSS at week 52 vs. baseline.¹⁸

FAST4WARD: A 24-week phase 3 trial in 220 adult patients living with active RA who had previously failed ≥1 DMARD and were randomised 1:1 to receive CIMZIA® 400 mg Q4W or placebo. The primary endpoint was ACR20 at week 24.19
Study 014: A 24-week phase 3 study in 247 adult patients living with active RA who were randomised 1:1 to receive CIMZIA® 400 mg Q4W or placebo. The primary endpoint was ACR20 at week 24.²⁰

CIMPASI 1 & 2: Two 48-week phase 3 studies in 461 adult patients (234 and 227, respectively) living with moderate-to-severe chronic PSO who were randomised 2:2:1 to receive CIMZIA® 400 mg Q2W, or CIMZIA® 200 mg Q2W, or placebo, with those patients randomised to CIMZIA® 200 mg Q2W receiving a loading dose of CIMZIA® 400 mg at week 0, week 2, and week 4. At week 16, patients who achieved PASI50 continued treatment through week 48. The coprimary endpoints were PASI75 and a PGA 0/1 with ≥2 improvement at week 16.²¹

CIMPACT: A phase 3 study in 559 adult patients living with moderate-to-severe chronic PSO who were randomised 3:3:1:3 to receive CIMZIA® 400 mg Q2W or CIMZIA® 200 mg Q2W (after loading doses of CIMZIA® 400 mg at week 0, week 2, and week 4) or placebo for 16 weeks, or etanercept 50 mg twice weekly for 12 weeks. Patients who achieved PASI75 at week 16 vs. baseline were rerandomised to CIMZIA® or placebo for 32 weeks. The primary endpoint was PASI75 at week 12 vs. placebo.²²

1. CIMZIA® Summary of Product Characteristics, July 2022. Last accessed 22/12/2022. Access the CIMZIA® SmPC

2. Mariette X, Förger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018 Feb;77(2):228-233.

3. Clowse ME, Förger F, Hwang C, et al. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017 Nov;76(11):1890-1896.

4. Rusman T, van Vollenhoven RF, van der Horst-Bruinsma IE. Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky. Curr Rheumatol Rep. 2018 May 12;20(6):35.

5. Landewé RB, van der Heijde D, Dougados M, et al. Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction. Ann Rheum Dis. 2020 Jul;79(7):920-928.

6. van der Heijde D, Baraliakos X, Hermann KA et al. Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial. Ann Rheum Dis. 2018 May;77(5):699-705.

7. van der Heijde D, Dougados M, Landewé R, et al. Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA. Rheumatology (Oxford). 2017 Sep 1;56(9):1498-1509.

8. van der Horst-Bruinsma I, van Bentum R, Verbraak FD, et al. The impact of certolizumab pegol treatment on the incidence of anterior uveitis flares in patients with axial spondyloarthritis: 48-week interim results from C-VIEW. RMD Open. 2020 Apr;6(1):e001161.

9. Sieper J, Kivitz A, van Tubergen A, et al. Impact of Certolizumab Pegol on Patient-Reported Outcomes in Patients With Axial Spondyloarthritis. Arthritis Care Res (Hoboken). 2015 Oct;67(10):1475-80.

10. van der Heijde D, Deodhar A, FitzGerald O, et al. 4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis. RMD Open. 2018 Mar 14;4(1):e000582.

11. Walsh JA, Gottlieb AB, Hoepken B, et al. Efficacy of certolizumab pegol with and without concomitant use of disease-modifying anti-rheumatic drugs over 4 years in psoriatic arthritis patients: results from the RAPID-PsA randomized controlled trial. Clin Rheumatol. 2018 Dec;37(12):3285-3296.

12. Keystone E, Landewé R, van Vollenhoven R, et al. Long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the RAPID 1 trial and open-label extension. Ann Rheum Dis. 2014 Dec;73(12):2094-100.

13. Fleischmann R, van Vollenhoven RF, Vencovský J, et al. Long-Term Maintenance of Certolizumab Pegol Safety and Efficacy, in Combination with Methotrexate and as Monotherapy, in Rheumatoid Arthritis Patients. Rheumatol Ther. 2017 Jun;4(1):57-69.

14. Gordon KB, Warren RB, Gottlieb AB, et al. Long-term efficacy of certolizumab pegol for the treatment of plaque psoriasis: 3-year results from two randomized phase III trials (CIMPASI-1 and CIMPASI-2). Br J Dermatol. 2021 Apr;184(4):652-662.

15. Landewé R, Braun J, Deodhar A, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis. 2014 Jan;73(1):39-47.

16. van der Horst-Bruinsma IE, van Bentum RE, Verbraak FD, et al. Reduction of anterior uveitis flares in patients with axial spondyloarthritis on certolizumab pegol treatment: final 2-year results from the multicenter phase IV C-VIEW study. Ther Adv Musculoskelet Dis. 2021 Mar 29;13:1759720X211003803.

17. Mease PJ, Fleischmann R, Deodhar AA, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014 Jan;73(1):48-55.

18. Keystone E, Heijde Dv, Mason D Jr et al. Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2008 Nov;58(11):3319-29.

19. Fleischmann R, Vencovsky J, van Vollenhoven RF, et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis. 2009 Jun;68(6):805-11.

20. Choy E, McKenna F, Vencovsky J, et al. Certolizumab pegol plus MTX administered every 4 weeks is effective in patients with RA who are partial responders to MTX. Rheumatology (Oxford). 2012 Jul;51(7):1226-34.

21. Gottlieb AB, Blauvelt A, Thaçi D, L et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol. 2018 Aug;79(2):302-314.e6.

22. Lebwohl M, Blauvelt A, Paul C, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks of a phase 3, multicenter, randomized, double-blind, etanercept- and placebo-controlled study (CIMPACT). J Am Acad Dermatol. 2018 Aug;79(2):266-276.e5.

23. Curtis JR, Mariette X, Gaujoux-Viala C, et al. Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn's disease: a pooled analysis of 11 317 patients across clinical trials. RMD Open. 2019 May 31;5(1):e000942.