Effective Date: 10/01/2010
Title: Cimzia (Certolizumabpegol)
Revision Date: 02/01/2019
CPT Code(s): J0717
will apply to all services performed on or after the above revision date which
will become the new effective date.
services referred to in this policy that were performed before the revision
date, contact customer service for the rules that would apply.
used to treat severe Rheumatoid Arthritis, Crohn’s disease, ankylosing
spondylitis, psoriasis, and psoriatic arthritis.
Cimzia is a
specialty drug and must be obtained through the contracted specialty pharmacy.
covered conditions, Cimzia will be covered only when member does not have active
infection and has been tested for tuberculosis.
Certolizumab Pegol (Cimzia®) is considered medically necessary for members 18
years of age or older with moderately-to-severely active Crohn`s disease as
manifested by any of the following signs/symptoms:
Extra-intestinal manifestations: arthritis or spondylitis; and
For adults 18 years of
age or older with moderately to severely active rheumatoid arthritis (at least 6
swollen and tender joints, at least 45 minutes of morning stiffness, and
elevated ESR or CRP unless patient on corticosteroids)
For adults 18 years of
age or older with active ankylosing spondylitis AND
18 years of age or older with active psoriatic arthritis AND
At least 3
swollen and tender joints
adults 18 years of age or older with moderate-to-severe plaque psoriasis AND
psoriasis has been present for more than 1 year AND
percent or more body surface area (BSA) is affected by plaque psoriasis AND
has a history of failure of at least a 3-month trial of, contraindication, or
intolerance to ALL of the following:
therapy with corticosteroids, Vitamin D analogs (e.g. calcitriol, calcipotriene),
calcineurin inihibtor (e.g. tacrolimus, pimecrolimus), or salicylic acid
combination product AND
Phototherapy of at least 3 months duration with narrow-band UVB (in the office
or at home) used alone or in combination with topical or systemic therapy (See
BI 029 for additional information regarding UV light therapy) This requirement
may be waived in any of the following situations: a) history or presence of
melanoma or other skin cancer, lupus erythematosus, or xeroderma pigmentosum, b)
psoriasis involving areas around the eye where eye protection may cause blockage
of phototherapy to affected area, c) documented systemic disease involving the
joints (meeting specific criteria for psoriatic arthritis), or 4) very severe
plaque thickness or scaling (4 on a scale of 0 to 4) AND
Systemic therapy of at least 3 months duration with methotrexate or other
non-biologic DMARD. This requirement may be waived in any of the following
situations: a) member has chronic hepatic disease, b) member has acquired
immunodeficiency syndrome (AIDS), c) member is pregnant or breast-feeding, or d)
member has anemia, neutropenia, or thrombocytopenia
Used In This BI:
J0718 Injection Certolizumab Pegol, 1mg (code deleted 1-1-14)
J0717 Injection Certolizumab Pegol, 1mg
Cimzia is considered experimental/Investigative for all other uses.
Because there are no
studies supporting concomitant therapy with any two biologics, and because
combinations have resulted in increases in serious infections, only one biologic
will be covered at a time.
(Cimzia®) (UCB, Inc., Smyrna, GA) is the first PEGylated anti- tumor necrosis
factor (TNF)-alpha monoclonal antibody that has a high affinity for human
TNF-alpha and selectively targets TNF-alpha in inflamed tissue. Excess
TNF-alpha production has been implicated in a wide variety of diseases,
including Crohn`s disease, rheumatoid arthritis and other autoimmune diseases.
In April 2008, the U.S.
Food and Drug Administration (FDA) approved Certolizumab pegol for adults with
moderately-to-severely active Crohn`s disease who have not responded to
conventional therapies. The approval of Certolizumab pegol was based on safety
and efficacy data from clinical trials in more than 1,500 patients with Crohn`s
The PEGylated Antibody
Fragment Evaluation in Crohn`s Disease: Safety and Efficacy (Precise) program
enrolled more than 1,300 patients in 4 trials and evaluated the safety and
efficacy of Certolizumab pegol. The Precise 1 and Precise 2 studies were 26-week
trials that evaluated induction and short-term maintenance of remission. Outcome
data from the Precise 3 and Precise 4 studies, designed to evaluate long-term
maintenance of remission, have not yet been published.
The Precise 1 trial, a
placebo-controlled phase IIII study, stratified patients (n = 662) according to
baseline levels of C-reactive protein (CRP). Patients were randomly assigned to
receive either 400 mg of Certolizumab pegol or placebo subcutaneously at weeks
0, 2, and 4 and then every 4 weeks. Primary endpoints were the induction of a
response at week 6 and a response at both weeks 6 and 26. Among patients with a
baseline CRP level of at least 10 mg per liter, 37% of patients in the
Certolizumab group had a response at week 6, as compared with 26% in the placebo
group. At both weeks 6 and 26, the corresponding values were 22% and 12%,
respectively. In the overall population, response rates at week 6 were 35% in
the Certolizumab group and 27% in the placebo group; at both weeks 6 and 26, the
response rates were 23% and 16%, respectively. At weeks 6 and 26, the rates of
remission in the two groups did not differ significantly. Serious adverse
events were reported in 10% of patients in the Certolizumab group and 7% of
those in the placebo group; serious infections were reported in 2% and less than
1%, respectively. In the Certolizumab group, antibodies to the drug developed
in 8% of patients, and antinuclear antibodies developed in 2%. The authors
concluded that in patients with moderate-to-severe Crohn`s disease, induction
and maintenance therapy with Certolizumab pegol was associated with a modest
improvement in response rates, as compared with placebo, but with no significant
improvement in remission rates (Sandborn, et al., 2007).
The Precise 2 trial, a
placebo-controlled study, evaluated the efficacy of Certolizumab pegol
maintenance therapy in adults (n = 668) with moderate-to-severe Crohn`s
disease. Certolizumab pegol (400 mg) was administered subcutaneously at weeks
0, 2, and 4 as induction therapy. Patients with a clinical response (defined as
reduction of at least 100 from the baseline score on the Crohn`s Disease
Activity Index [CDAI]) at week 6 were stratified according to their baseline CRP
level and were randomly assigned to receive 400 mg of Certolizumab pegol or
placebo every 4 weeks through week 24, with follow-up through week 26. Among
patients with a response to induction therapy at week 6 (n= 428 or 64%), the
response was maintained through week 26 in 62% of patients with a baseline CRP
level of at least 10 mg per liter (the primary endpoint) who were receiving
Certolizumab pegol (versus 34% of those receiving placebo) and in 63% of
patients in the intention-to-treat population who were receiving Certolizumab
pegol (versus 36% receiving placebo). Among patients with a response to
induction therapy at week 6, remission (defined by a CDAI score of 150) at week
26 was achieved in 48% of patients in the Certolizumab group and 29% of those in
the placebo group. The use of immunosuppressant’s, corticosteroids, and previous
treatment with infliximab were not demonstrated to affect the response rate.
Serious infections, including one case of pulmonary tuberculosis, occurred in 3%
of patients receiving Certolizumab pegol and in less than 1% of patients
receiving placebo. Antinuclear antibodies developed in 8% of the patients in
the Certolizumab group; antibodies against Certolizumab pegol developed in 9% of
all patients who entered the induction phase. The authors concluded that
patients with moderate-to-severe Crohn`s disease who had a response to induction
therapy with 400 mg of Certolizumab pegol were more likely to have a maintained
response and a remission at 26 weeks with continued Certolizumab pegol treatment
than with a switch to placebo.
Certolizumab pegol was
approved by the FDA on April 24, 2009 for adults with moderately-to-severely
active rheumatoid arthritis (RA). It can be administered as combination therapy
with methotrexate (MTX) or as monotherapy. The recommended dose for patients
with moderately-to-severely active RA is 400 mg initially and at weeks 2 and 4,
followed by 200 mg every other week. For maintenance dosing, 400 mg every 4
weeks can be considered. It is self-administer by subcutaneous injection.
According to the prescribing information, Certolizumab pegol should not be used
in combination with biological disease-modifying Antirehumatic drugs (DMARDs) or
other TNF blocker therapies.
The FDA approval is based
on data from 4 multi-center placebo-controlled phase III trials, involving more
than 2,300 patients aged 18 years or older with moderately-to-severely active
RA. Patients who received Certolizumab pegol together with MTX, experienced a
significant reduction in the signs and symptoms of RA at week 24 with some
showing clinical responses within 1 to 2 weeks, compared with MTX alone.
Additionally, radiographic data showed Certolizumab pegol, together with MTX,
inhibited progression of joint damage, with a significantly smaller change from
baseline in modified Total Sharp Score (TSS) at 24 and 52 weeks of treatment,
compared with MTX alone (p < 0.001).
Keystone, et al. (2008) evaluated the safety and efficacy of 2 dosage regimens
of Certolizumab pegol as adjunctive therapy to MTX in patients with active RA
who had an inadequate response to MTX therapy alone. In this 52-week, phase
III, multi-center, randomized, double-blind, placebo-controlled, parallel-group
trial, 982 patients were randomized 2:2:1 to receive treatment with 400 mg of
Certolizumab pegol as an initial dosage and at weeks 2 and 4, with a subsequent
dosage of 200 mg or 400 mg given every 2 weeks, plus MTX, or placebo plus MTX.
Co-primary endpoints were the response rate at week 24 according to the American
College of Rheumatology 20% criteria for improvement (ACR20) and the mean change
from baseline in the modified TSS at week 52. At week 24, ACR20 response rates
using non-responder imputation for the Certolizumab pegol 200-mg and 400-mg
groups were 58.8% and 60.8%, respectively, as compared with 13.6% for the
placebo group. Differences in ACR20 response rates versus placebo were
significant at week 1 and were sustained to week 52 (p < 0.001). At week 52,
mean radiographic progression from baseline was reduced in patients treated with
200 mg of Certolizumab pegol (0.4 Sharp units) or 400 mg (0.2 Sharp units) as
compared with that in placebo-treated patients (2.8 Sharp units) (p < 0.001 by
rank analysis). Improvements in all ACR core set of disease activity measures,
including physical function, were observed by week 1 with both Certolizumab
pegol dosage regimens. Most adverse events were mild or moderate. The authors
concluded that 200 mg or 400 mg of Certolizumab pegol plus MTX resulted in a
rapid and sustained reduction in RA signs and symptoms, inhibited the
progression of structural joint damage, and improved physical function as
compared with placebo plus MTX treatment in RA patients with an incomplete
response to MTX.
College of Rheumatology; Model Biologics Policy 2010.
Furst DA, Bharat A, et al. 2012 Update of the 2008 American College of
Rheumatology Recommendations for the Use of Disease-Modifying Antirehumatic
Drugs and Biologic Agents in the Treatment of Rheumatoid Arthritis. Arthritis
Care & research. 2012; 64(5):625-639.
U.S. Food and Drug Administration (FDA). FDA
approves Cimzia to treat Crohn`s disease. FDA News. Rockville, MD; April 22,
2008. Available at: http://www.fda.gov/bbs/topics/NEWS/2008/NEW01821.html. Accessed
May 20, 2008.
Choy EH, Hazleman B, Smith M, et al. Efficacy of a
novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid
arthritis: A phase II double-blinded, randomized, dose-escalating trial.
Rheumatology (Oxford). 2002; 41(10):1133-1137.
National Horizon Scanning Centre (NHSC).
Certolizumab pegol for moderate to severe Crohn`s disease - horizon scanning
review. Birmingham, UK: NHSC; 2004.
National Horizon Scanning Centre (NHSC).
Certolizumab pegol (Cimzia) for rheumatoid arthritis - horizon scanning review.
Birmingham, UK: NHSC; 2005.
Schreiber S, Rutgeerts P, Fedorak RN, et al;
CDP870 Crohn`s Disease Study Group. A randomized, placebo-controlled trial of
Certolizumab pegol (CDP870) for treatment of Crohn`s disease. Gastroenterology.
Sandborn WJ, Feagan BG, Stoinov S, et al; PRECISE
1 Study Investigators. Certolizumab pegol for the treatment of Crohn`s
disease. N Engl J Med. 2007; 357(3):228-238.
Schreiber S, Khaliq-Kareemi M, Lawrance IC, et al;
PRECISE 2 Study Investigators. Maintenance therapy with Certolizumab pegol for
Crohn`s disease. N Engl J Med. 2007; 357(3):239-250.
Behm BW, Bickston SJ. Tumor necrosis factor-alpha
antibody for maintenance of remission in Crohn`s disease. Cochrane Database Syst
Rev. 2008 ;( 1):CD006893.
Rutgeerts P, Schreiber S, Feagan B, et al; CDP870
Crohn`s Disease Study Group. Certolizumab pegol, a monthly subcutaneously
administered Fc-free anti-TNFalpha, improves health-related quality of life in
patients with moderate to severe Crohn`s disease. Int J Colorectal Dis. 2008;
Keystone E, Heijde D, 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;
Smolen J, Landewé RB, Mease P, et al. Efficacy and
safety of Certolizumab pegol plus methotrexate in active rheumatoid arthritis:
The RAPID 2 study. A randomized controlled trial. Ann Rheum Dis. 2009;
R, Vencovsky J, van Vollenhoven RF, Borenstein D, et al. Efficacy and safety of
Certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid
arthritis failing previous disease-modifying Antirehumatic therapy: The
FAST4WARD study. Ann Rheum Dis. 2009; 68(6):805-811.
Cimzia Product Information. UCB, Inc. June 2018.
Application to Products
This policy applies to all health plans administered by QualChoice, both those insured by QualChoice and those that are self-funded by the sponsoring employer, unless there is indication in this policy otherwise or a stated exclusion in your medical plan booklet. Consult the individual plan sponsor Summary Plan Description (SPD) for self-insured plans or the specific Evidence of Coverage (EOC) for those plans insured by QualChoice. In the event of a discrepancy between this policy and a self-insured customer’s SPD or the specific QualChoice EOC, the SPD or EOC, as applicable, will prevail. State and federal mandates will be followed as they apply.
Changes: QualChoice reserves the right to alter, amend, change or supplement benefit interpretations as needed.