Cimzia should only be used during pregnancy if clinically needed.¹ Data from more than 500 prospectively collected pregnancies exposed to Cimzia with known pregnancy outcomes, including more than 400 pregnancies exposed during the first trimester, showed no indication of demonstrated malformative effect from Cimzia.¹

However, the available clinical experience is too limited to, with a reasonable certainty, conclude that there is no increased risk associated with Cimzia administration during pregnancy.

Cimzia has a unique structure, it is a novel FC-free, PEGylated, anti-tumour necrosis factor α (anti-TNFα) monoclonal antibody.⁷ The FC region is responsible for facilitating active placental transfer,⁸ therefore, removing the FC region prevents Cimzia form being actively transported across the placental membrane.^10,11,12 Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn.

Studies have demonstrated that Cimzia undergoes none to minimal placenta transfer, due to the lack of an FC region. This means that Cimzia that be used during pregnancy, when clinically needed, and allows for treatment continuity.^1,12,13

Cimzia can also be used during breastfeeding.¹ In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol from plasma to breast milk was observed.⁴ The percentage of the maternal certolizumab pegol dose reaching an infant during a 24-hour period was estimated at 0.04% to 0.30%.⁴ In addition, since certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, the absolute bioavailability is expected to be very low in a breasted infant.¹³

Cimzia is the first and only biologic with an EMA approved label to demonstrate sustained remission at a reduced maintenance does in severe, active axSpA

The C-axSpAnd study was a double-blind placebo-controlled trial to investigate the impact of Cimzia in patients with nr-axSpA with objective signs of inflammation. Patients were randomised 1:1 to receive placebo (n=158) or Cimzia (n=159, 400 mg at weeks 0, 2, and 4, then 200mg every 2 weeks) in addition to non-biological background medication. The study demonstrated improvements in clinical efficacy. Objective signs of inflammation were maintained to week 52 in Cimzia treated to non-radiographic axial spondyloarthritis patients. Adding Cimzia to background medication demonstrated a significant improvement in ASDAS-MI and ASAS40 at week 52 compared to adding placebo in patients with active non-radiographic axSpA. Post hoc analysis indicate that early Cimzia treatment for nr-axial spondyloarthritis (axSpA) may be beneficial to patients.¹

The C-OPTIMISE study compared dose continuation, dose reduction and discontinuation in patients achieving clinical remission with Cimzia. After a 48 week, open label period during which time, all patients received 200mg Cimzia every 2 weeks, the 323 patients achieving sustained remission were randomised (double-blind) to Cimzia 200mg every 2 weeks (n=104), Cimzia 200mg every 4 weeks (n=105) or placebo (n=104), for a further 48 weeks.¹⁴

Figure 1.
Patients free of flares during the maintenance period of C-OPTIMISE. Panel A shows the proportions of patients who did not experience flares following randomisation to CZP full maintenance dose (200mg Q2W), CZP reduced maintenance dose (200mg Q4W) or placebo. Panel B shows a Kaplan-Meier plot of time to flare. Missing values were imputed using non-responder imputation. Flare was defined as ASDAS ≥2.1 at two consecutive visits, or ASDAS ≥3.5 at any visit. CZP, certolizumab pegol; Q2W, every 2 weeks; Q4W, every 4 weeks.
Adapted from: Landewé et al., 2020.

The RAPID-axSpA study randomised 325 patients with 218 (97/325 of which had non-radiographic disease) receiving Cimzia (double-blind and placebo-controlled to week 24, dose-blind to week 48 and open-label to week 204).^15,16,17

Radiographic data was examined for all Cimzia-treated patients with ≥1 mSASSS assessment (X-ray set), including those rerandomised from placebo. 199(63.2%) completed the study to week 204 and 158 patients had valid MRI assessments at baseline and ≥1 other timepoint (MRI set) (n=158).¹⁷

Figure 2.
Study design. RAPID-axSpA trial design to week 24 of an ongoing 204-week trial. axSpA, axial spondyloarthritis; CZP, certolizumab pegol; PBO, Placebo; LD, loading dose; Q2W, every 2 weeks; Q4W, every 4 weeks; sc, subcutaneous.
Adapted from: Landewé et al., 2013.

RAPID-axSpA is the first long-term, large study to investigate imaging results in AS and nr-axSpA subpopulations when treated with a TNF-inhibitor. Here, Cimzia treatment rapidly improved axSpA inflammation of the spine and sacroiliac (SI) joints as observed using MRI in patients with AS and nr-axSpA. These improvements were maintained to week 204, with similar responses obeserved in both radiographic and non-radiographic axSpA patients.^15,16,17

Figure 3.
Radiographic imaging results of the spine to week 204. AS, ankylosing spondylitis; LS, least squares; mSASSS, modified Stoke Ankylosing Spondylitis Spine Score; nr-axSpA, non-radiographic axial spondylitis.
Adapted from: Van der Heijde et al., 2018.

The RAPID-axSpA study randomised 325 patients with 218 (97 of which had non-radiographic disease) receiving Cimzia (double blind and placebo-controlled to week 24, dose-blind to week 48 and open-label to week 204). In addition to the primary outcome measure of ASAS response other specific patient reported outcomes were also recorded.¹⁸

Figure 4.
Change from baseline (CFB) in fatigue (B). and sleep problems (Medical Outcomes Study Sleep Problems Index || [MOS-SPI] (C). Number of patients for placebo (PBO), certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W), and CZP 400 mb every 4 weeks (Q4W), respectively, are total axial spondyloarthritis (axSpA): 106, 111 and 107; AS: 57, 65, and 56; and non-radiographic (nr) axSpA: 49, 46, and 51. AS = ankylosing spondylitis; * = P < 0.001; ✝ = P < 0.05 CZP groups vs. PBO.¹⁸
Adapted from: Sieper et al., 2015.

At week 24, more Cimzia-treated axSpA patients reported improvements greater or equal to the minimum clinically important difference (MCID) for sleep compared to placebo. At week 24, the proportion of patients achieving greater or equal to the MCID for Cimzia 200mg every 2 weeks and Cimzia 400mg every 4 weeks versus placebo was 57.7% and 61.7% versus 22.4% (P>0.001).¹⁸

Figure 5.
Change from baseline (CFB) in total back pain (numeric rating scale [NRS]) (A) NRS.* = P < 0.001; ✝ = P < 0.05 CZP groups vs. PBO.
Adapted from: Sieper et al., 2015.

At week 24, more Cimzia-treated axSpA patients reported improvements greater or equal to the minimum clinically important difference (MCID) for total back pain compared to placebo. At week 24, the proportion of patients achieving greater or equal to the MCID for Cimzia 200mg every 2 weeks and Cimzia 400mg every 4 weeks versus placebo was 80.2% and 77.6% versus 35.8% (P>0.001).¹⁶

Cimzia significantly reduced acute anterior uveitis flares in axSpA

The C-VIEW study recruited 89 patients with a diagnosis of axSpA and a previous history of acute anterior uveitis (AAU). These patients were treated with Cimzia and the incidence of uveitis flares before and after treatment were recorded and compared.¹⁹

Cimzia reduced the incidence of AAU by 87%. AAU incidence rate per 100 PY decreased from 146.6 (95% CI 121.5 to 175.3) to 18.7 per 100 PY (95% CI 10.5 to 30.9).¹⁹

Cimzia promotes total resolution of enthesitis

The RAPID-axSpA study randomised 325 patients with 218 (97/325 of which had non-radiographic disease (nr-axSpA)) receiving Cimzia (double-blind and placebo-controlled to week 24, dose-blind to week 48 and open label to week 204).^15,16,17

One of the secondary endpoints reported was the total resolution of enthesitis.²⁰

Figure 6.
RAPID-axSpA total resolution of enthesitis by subpopulation to week 204. Efficacy in clinical and patient-reported outcomes (certolizumab pegol-randomized group, doses combined).
Adapted from: Van der Heijde et al., 2017.

At 4 years, total resolution of enthesitis was seen in²⁰:

• 66% of AS (n=58) and 61% of nr-axSpA (n=46) patients with recorded enthesitis at baseline
• 71% of AS (n=17) and 78% of nr-axSpA (n=18) patients with recorded heel enthesitis at baseline

Adverse reactions in clinical trials and post-marketing¹

For more detailed adverse reactions information, see the safety profile page.
Common* adverse reactions based primarily on experience from the placebo-controlled clinical trials and post-marketing cases at least possibly related to Cimzia are listed below.

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