ARTLEGIA
Olokizumab
IL-6 inhibitor for the treatment of rheumatoid arthritis, blocking the cytokine, not the receptors
Olokizumab is an original molecula of the R-Pharm group of companies
About olokizumab
Pharmacological properties:
Olokizumab is a humanized (containing grafted complementarity determining regions (CDRs)) monoclonal antibody of the immunoglobulin (Ig) G4/kappa isotype.
Olokizumab selectively binds to human IL-6 and effectively neutralizes the effects of IL-6 in vivo and in vitro. Obtained data indicate that olokizumab does not significantly bind to other molecules of the IL-6 family and does not affect their functioning, nor does it activate the IL-6 signaling pathway.
Mechanism of action olokizumab
INDICATIONS FOR USE
AND CONTRAINDICATIONS
AND CONTRAINDICATIONS
In patients with a history of serious or opportunistic infections; with concomitant diseases and conditions that are risk factors for developing infections (diabetes, renal failure, use of immunosuppressive drugs, elderly age, etc.).
In patients exposed to tuberculosis. The risk-benefit ratio of the drug should be evaluated before using Olokizumab in such patients.
In patients with a history of diverticulitis or intestinal perforations and other risk factors for intestinal perforation.
In patients with hepatic impairment or hepatic failure.
In patients exposed to tuberculosis. The risk-benefit ratio of the drug should be evaluated before using Olokizumab in such patients.
In patients with a history of diverticulitis or intestinal perforations and other risk factors for intestinal perforation.
In patients with hepatic impairment or hepatic failure.
A history of hypersensitivity to olokizumab or any component of the drug.
Active infectious diseases (including tuberculosis).
Children under 18 years of age.
Hereditary fructose intolerance (the drug contains sorbitol).
Breastfeeding..
Active infectious diseases (including tuberculosis).
Children under 18 years of age.
Hereditary fructose intolerance (the drug contains sorbitol).
Breastfeeding..
Treatment of patients aged 18 years or older with moderate to severe rheumatoid arthritis in combination with methotrexate and who have an inadequate response to methotrexate or tumor necrosis factor inhibitor (TNFi) therapy.
Olokizumab is recommended for patients with moderate to highly active rheumatoid arthritis when methotrexate or TNF-α 1 inhibitors are insufficiently effective
Reliably better efficiency compared with placebo, at least comparable effectiveness with adalimumab in combination with methotrexate
Blockade of the cytokine itself, not the receptor
Studied safety profile corresponding to the IL-6 class corresponding to the IL-61-4 class
Improving the quality of life of patients
Convenient dosing regimen, small injection volume
Clinical trials
CLINICAL EFFICACY DATA
Data on the efficacy and safety of Olokizumab were obtained within the framework of:
- Preclinical studies
- Within the framework of Phase I and II clinical trials
- Three international Phase III clinical trials involving 2,444 patients over 18 years of age with moderate to severe rheumatoid arthritis (CREDO 1, 2, 3)
- An open-label long-term study of patients (CREDO 4) who completed one of the Phase III clinical trials
Multi-center, open-label, Phase III study to assess olokizumab efficacy and safety in patients with moderate to severely active rheumatoid arthritis (CREDO 4), protocol CL04041024; permission of the Russian Ministry of Health No. 670 dd 20/09/2016.
Phase III, randomized, double-blind, placebo-controlled, multi-center study in parallel groups to assess efficacy and safety of olokizumab in patients with moderate to severe rheumatoid arthritis that is not sufficiently controlled with alpha tumor necrosis factor inhibitors (CREDO 3), protocol No. CL04041025; permission of the Russian Ministry of Health No. 389 dd 07/06/2016.
Phase III, randomized, double-blind, multi-center study in parallel groups with placebo and active control for assessment of efficacy and safety of olokizumab in patients with moderate to severe rheumatoid arthritis, which is insufficiently controlled with Methotrexate (CREDO 2), protocol No. CL04041023; permission of the Russian Ministry of Health No. 356 dd 24/05/2016.
Phase III, randomized, double-blind, placebo-controlled, multi-center study in parallel groups to assess efficacy and safety of olokizumab safety in patients with moderate to severe rheumatoid arthritis that is not sufficiently controlled with Methotrexate (CREDO 1), protocol No. CL04041022; permission of the Russian Health Ministry No. 324 dd 13/05/2016.
Data on the clinical profile of olokizumab were obtained from the large-scale CREDO clinical trial program, which enrolled 2444 patients from 19 countries worldwide
CREDO RESEARCH PROGRAM
RCT
2444
Primary endpoints
(12 weeks)
(12 weeks)
Secondary endpoints
(12, 24 weeks)
(12, 24 weeks)
CREDO 1
CREDO 2
CREDO 3
428 patients
with insufficient efficiency MTX
1648 patients
with insufficient efficiency of MTX and active (adalimumab) control
368 patients
with insufficient effectiveness of TNFα
ACR20
ACR20
ACR20
ACR50
DAS28<3,2
CDAI≤2,8
HAQ-DI
DAS28<3,2
CDAI≤2,8
HAQ-DI
ACR50
DAS28<3,2
CDAI≤2,8
HAQ-DI
DAS28<3,2
CDAI≤2,8
HAQ-DI
ACR50
DAS28<3,2
CDAI≤2,8
HAQ-DI
DAS28<3,2
CDAI≤2,8
HAQ-DI
patients
2105
375 patients
continued treatment
1429 patients
continued treatment
302 patients
continued treatment
patients
included in CREDO 4
Results for all endpoints were achieved and were statistically significantly superior to placebo, and in CREDO2 were comparable to active control
CREDO 4 – ------ of patients continued therapy
96%
- Long-term (up to 82 weeks of observation) retention of patients on therapy and maintenance of the achieved response according to the main effectiveness indicators
- No new safety signals compared to other IL-6 drugs
- Low immunogenicity of olokizumab throughout the observation period
-------- of patients continued therapy and observation for 126 weeks in the CREDO clinical program
81,2 %
CREDO 1
Both treatment regimens were comparable in effectiveness
Evaluated: ACR 20,50,70, DAS28; HAQ-DI; CDAI; PRO
Efficacy and safety were assessed every 2 weeks
There was no additional therapy for olokizumab (required for placebo)
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy. Treatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens.
3 countries globally (Belarus, Bulgaria, Russian Federation)
3 countries globally (Belarus, Bulgaria, Russian Federation)
DATA ON THE CLINICAL EFFICACY OF OLOKIZUMAB IN CREDO 1
ACR20
Primary endpoints
ACR50
Secondary endpoints
DAS28<3.2
Secondary endpoints
CDAI ≤ 2.8
Secondary endpoints
HAQ-DI
Secondary endpoints
Both regimens (every 2 weeks and every 4 weeks) in patients with inadequate response to methotrexate are significantly better than placebo on all endpoints
CREDO 2
Both treatment regimens were comparable in effectiveness
Evaluated: ACR 20,50,70, DAS28; HAQ-DI; CDAI; PRO
Efficacy and safety were assessed every 2 weeks
No additional therapy was available when taking olokizumab (required when taking placebo)
1 648 patients with ineffective methotrexate and active control (adalimumab)
A Randomized, Double-Blind, Parallel-Group, Placebo- and Active-Controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Methotrexate Therapy. In patients with rheumatoid arthritis who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing an ACR20 response at 12 weeks. Larger and longer trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis.
18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America)
18 countries globally (in US, European Union (EU),United Kingdom (UK), Russian Federation, Asia, Latin America)
CREDO 2 Conclusions:
1
2
Both therapy regimens in patients with inadequate response to methotrexate have an advantage over placebo
The use of olokizumab under any of the regimens was accompanied by the development of clinical and laboratory improvement, which was not inferior to the effects of adalimumab in terms of its severity
Superior to placebo and non-inferior to adalimumab in combination with methotrexate in terms of response time to therapy and its severity
!
DATA ON THE CLINICAL EFFICACY OF OLOKIZUMAB IN CREDO 2
ACR20
Primary endpoints
ACR50
Secondary endpoints
DAS28<3.2
Secondary endpoints
CDAI ≤ 2.8
Secondary endpoints
HAQ-DI
Secondary endpoints
Both regimens have an advantage over placebo in patients with insufficient response to methotrexate. Not inferior to adalimumab in combination with methotrexate in terms of response to therapy and its severity
CREDO 3
Both treatment regimens were comparable in effectiveness
Evaluated: ACR 20,50,70, DAS28; HAQ-DI; CDAI; PRO
Efficacy and safety were assessed every 2 weeks
No additional therapy was available when taking olokizumab (required when taking placebo)
368 patients with inadequate response to prior biologic therapy
A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Inadequately Controlled by Tumor Necrosis Factor Alpha (TNF-α) Inhibitor Therapy. Direct inhibition of IL-6 with OKZ resulted in significant improvements in the signs and symptoms of rheumatoid arthritis compared with PBO in TNF-IR patients with a similar safety profile as observed for monoclonal antibodies to the IL-6 receptor.
11 countries globally (in US, EU, Russian Federation, Asia, Latin America, United Kingdom, United States)
11 countries globally (in US, EU, Russian Federation, Asia, Latin America, United Kingdom, United States)
DATA ON THE CLINICAL EFFICACY OF OLOKIZUMAB IN CREDO 3
ACR20
Primary endpoints
DAS28<3.2
Secondary endpoints
CDAI ≤ 2.8
Secondary endpoints
HAQ-DI
Secondary endpoints
Both therapy regimens were statistically more effective than placebo in achieving the primary and first secondary endpoints
When switching from placebo to olokizumab therapy at week 16 of the study, patients achieved a clinically meaningful response
When switching from placebo to olokizumab therapy at week 16 of the study, patients achieved a clinically meaningful response
CREDO 4. Study design
RA patients who completed a 24-week double-blind treatment period in one of three pivotal studies (CREDO-1, CREDO-2, CREDO-3)
A Multicenter, Open-Label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis.
18 countries globally (Argentina, Belarus, Brazil, Bulgaria, Colombia, Czechia, Estonia, Germany, Hungary, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Russian Federation, Taiwan, United Kingdom, United States).
18 countries globally (Argentina, Belarus, Brazil, Bulgaria, Colombia, Czechia, Estonia, Germany, Hungary, Korea, Republic of, Latvia, Lithuania, Mexico, Poland, Russian Federation, Taiwan, United Kingdom, United States).
DATA ON THE CLINICAL EFFICACY OF OLOKIZUMAB IN CREDO 4
ACR20
Primary endpoints
ACR50
Secondary endpoints
DAS28<3.2
Secondary endpoints
When Olokizumab 64 mg every 4 weeks was used, long-term (up to 82 weeks of follow-up) retention of patients on therapy and maintenance of achieved response in key efficacy measures (ACR20, DAS28) were observed
Long-term therapy on olokizumab provides control of rheumatoid arthritis according to CREDO4
2/3
Patients maintained low RA activity for more than 1,5 years
Safety information
Security Profile of IL-6 inhibitors: laboratory parameters
Class of IL-6 inhibitors
Adverse events
Olokizumab (pooled data RCT phase III)
N = 1 582
N = 1 582
Population of patients with RA on the background of MTX
N = 4543
N = 4543
Changes in laboratory parameters
Liver function
Lipids
Neutropenia and thrombocytopenia
Mean absolute neutrophil count at 12 weeks
Decreased in the first 4 weeks and then remained stable
Has not changed
Neutropenia at least once during treatment
4,17 %
1,54 %
Повышение АЛТ
11,4 %
3,9 %
Повышение АСТ
6,9 %
3,3 %
Increased bilirubin levels *
1,52 %
0,22 %
Increased levels of total cholesterol, triglycerides, LDL and/or HDL cholesterol
Hyperlipidemia
6,32 %
2,42 %
Total cholesterol, LDL and HDL cholesterol levels
Increased during the first 4 weeks of therapy and then remained stable
Didn't change
Increased levels of liver transaminases
A simultaneous rise in bilirubin and transaminases above the 3 upper limits of normal was observed in 1 patient in the OKZ q2w group.
The immunogenicity potential of olokizumab according to the CREDO program is low and does not raise safety concerns
CREDO 1
5.5% (15 study participants) developed antibodies to the drug
Neutralizing antibodies were absent
CREDO 2
Antibodies to the drug were recorded in 40 patients (4.5%) (in any titer at any time after the initial assessment)
Neutralizing antibodies were detected in only two patients (0.22%)
CREDO 3
In 23 patients (6.9%) antibodies to the drug were detected (in any titer at any time after the initial assessment)
None of the patients had neutralizing antibodies at any time during follow-up
CREDO 4
У 3% и у 4 % пациентов в группе 1р/4 нед и 1р/2 нед соответственно были выявлены АТ к препарату
Только у трёх пациентов выявились нейтрализующие АТ
General safety profile of IL-6 inhibitors
Well tolerated by patients;
safety profile is consistent with the IL-6 inhibitor class
safety profile is consistent with the IL-6 inhibitor class
Class of IL-6 inhibitors
Adverse events by organ system class/preferred term
Olokizumab (pooled data RCT phase III) N = 1 582
Population of patients with RA on the background of MTX N = 454
Infections and infestations
Malignant neoplasms
Gastrointestinal perforation
Increased risk of infections, serious infections and opportunistic infections, including tuberculosis, pneumonia and Herpes Zoster
Total infections
28.2 %
27.53 %
Serious infections
1.3 %
1,32 %
Opportunistic infections
0,6 %
0,22 %
Pneumonia
0,2 %
0,22 %
Pulmonary tuberculosis
0,1 %
0 %
Herpes zoster
0,4 %
0,22 %
The effect of therapy on the risk of malignant neoplasms is low
Neoplasms
0
0
Associated with an increased risk of lower gastrointestinal perforation with concomitant diverticulitis and/or use of NSAIDs
Gastrointestinal perforation
0
0
About rheumatoid arthritis
Key factors about RA
Rheumatic and musculoskeletal diseases (RMDs) comprise over 200 conditions affecting 120 million Europeans
Women are 2 to 3 time more likely to be affected by autoimmune for arthritis as men
RA is the most common autoimmune inflammatory form of arthritis
RA affects approximately 1 in 100 persons worldwide
Arthritis is the leading cause of disability among adults in the US
What is important for the doctor and patient in RA therapy?
Indices used by rheumatologists:
- ACR 20,50,70
- DAS28-CRP(ESR)
- SDAI
- CDAI
- ADL: Activities of daily living Boolean-1, Boolean remission with PGA ≤ 1, TJC ≤ 1, JC ≤ 1, and CRP ≤ 1
- Boolean-2: Boolean remission with PGA ≤ 2, TJC ≤ 1, SJC ≤ 1, and CRP ≤ 1
- Functional impairment according to the HAQ-DI index (from 0 to 3 points)
The current strategy for treating RA is based on the “Treat-to-target” principle
Main goals of pharmacotherapy of rheumatoid arthritis
Achieving remission (or low activity) of the disease*
*reduction of RA activity on the background of treatment during the first 3 months, associated with the development of remission, after 12-24 months
Reducing the risk of comorbid diseases that worsen the quality of life and prognosis in patients
Active prescription of anti-inflammatory therapy from the moment of diagnosis
"window of opportunity" up to 12 months from the diagnosis of RA - "early rheumatoid arthritis"
Frequent and objective monitoring of the patient's condition
at least every 3 months before remission is achieved, every 6 months after remission is achieved, using quantitative methods
Timely change of the treatment regimen
in case of insufficient response to therapy until the goal is achieved
Methodology for determining the DAS28 assessment of RA activity
DAS28
=
0,56√TGC
+
0,28√SJC
+
0,70lnESR
+
0,014PGA
DAS
disease activity score
TGC
tender joint count
SJC
swollen joint count 28 joints: shoulder, elbow, wrist, metacarpal-phalangeal, proximal interphalangeal, knee joints, which are primarily affected by RA and are well accessible for objective examination
ESR
erythrocyte sedimentation rate by the Westergren method
Ln
natural logarithm
PGA
patient global assessment on a 100 millimetre visual analogue scale
Inflammatory activity in RA depending on DAS28 index values:
DAS28 < 2.6
Remission
2.6 < DAS28 < 3.2
Low activity
3.2 < DAS28 < 5.1
Moderate activity
DAS28 > 5.1
High activity
CDAI – Clinical Disease Activity Index
CDAI
=
SJC (from 28)
+
TGC (from 28)
+
PGA
+
EGA
SJC
swollen joint count 28 joints: shoulder, elbow, wrist, metacarpal-phalangeal, proximal interphalangeal, knee joints, which are primarily affected by RA and are well accessible for objective examination
TGC
tender joint count
PGA
Patient Global disease Activity (patient’s self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)
EGA
Evaluator’s Global disease Activity (evaluator’s assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)
Formula for calculating:
PGA and EGA approximating on a scale 1-10 (on a VAS)
PGA and EGA approximating on a scale 1-10 (on a VAS)
Inflammatory activity in RA depending
on CDAI values:
2.8
Remission
2.8 – 10
Low Disease Activity
10 - 22
Moderate Disease Activity
22
High Disease Activity
Evaluation of therapy effectiveness according to CDAI index:
satisfactory effect - CDAI reduction by 7 points,
good effect - CDAI reduction by 15 points
satisfactory effect - CDAI reduction by 7 points,
good effect - CDAI reduction by 15 points
Visual analogue scale (VAS) for pain intensity
Achievement of remission or low disease activity
Patient-reported outcomes (PROs):
- functional impairment according to the HAQ-DI index (from 0 to 3 points)
- overall assessment of disease activity by the patient (PAAD; Patient's Global Assessment of Disease Activity, PtGA) (from 0 to 100 mm) using a visual analogue scale (VAS)
- total pain score according to VAS (from 0 to 100 mm)
- fatigue on the FACIT Fatigue (Functional Assessment of Chronic Illness Therapy) scale (0 to 52 points)
- quality of life according to the EQ-5D questionnaire (European Quality of Life-Five-Dimension Questionnaire)
- physical and mental components of the SF-36, including physical functioning, impact of physical condition on daily role functioning (work, daily duties), pain intensity, general health, vitality, social functioning, affective role functioning, and mental health
Instructions for preparing and injecting the drug
Take the Olokizumab vial or pre-filled syringe out of the refrigerator in advance: wait for approximately 30 minutes for it to warm to room temperature before preparing the injection.
Do not heat up the product.
Do not heat up the product.
Step 1
Wash your hands with warm water and soap, choose a flat, clean surface, carefully inspect the drug vial or pre-filled syringe and do not use it if:
The drug in a pre-filled syringe is ready for use.
Prepare the drug in a vial for use following the instructions
Prepare a 1-2 mL disposable hypodermic syringe, two disposable sterile needles (it is recommended to use an 18G needle to draw the drug from the vial and a 27G needle to perform a subcutaneous injection), 2 sterile alcohol wipes.
- it has been out of the refrigerator for more than 4 hours,
- it contains the wrong medication name,
- the shelf life indicated on the package has expired,
- the vial or pre-filled syringe is cracked, damaged or leaking,
- the solution is cloudy, discolored, or contains flakes or particles.
The drug in a pre-filled syringe is ready for use.
Prepare the drug in a vial for use following the instructions
Prepare a 1-2 mL disposable hypodermic syringe, two disposable sterile needles (it is recommended to use an 18G needle to draw the drug from the vial and a 27G needle to perform a subcutaneous injection), 2 sterile alcohol wipes.
Step 2
Join the capped thicker drawing needle with the syringe. Remove the plastic protective cap from the vial, clean the top of the rubber stopper with a sterile alcohol wipe.
Take the syringe in your right hand, remove the cap from the needle and insert the needle vertically into the center of the vial stopper so that the tip of the needle appears on the other side of the stopper.
Holding the syringe with your right hand, take the vial with your left hand and turn it upside down so that all the liquid collects over the stopper. Pulling the plunger of the syringe down, draw the entire contents of the vial into the syringe.
Pull the needle out of the vial and place the cap back on it. Without removing the cap, replace it with a hypodermic needle. Dispose of the used drawing needle into the sharps container
Take the syringe in your right hand, remove the cap from the needle and insert the needle vertically into the center of the vial stopper so that the tip of the needle appears on the other side of the stopper.
Holding the syringe with your right hand, take the vial with your left hand and turn it upside down so that all the liquid collects over the stopper. Pulling the plunger of the syringe down, draw the entire contents of the vial into the syringe.
Pull the needle out of the vial and place the cap back on it. Without removing the cap, replace it with a hypodermic needle. Dispose of the used drawing needle into the sharps container
Important!
Do not perform the injection with the drawing needle as this may cause pain and damage at the injection site.
Do not perform the injection with the drawing needle as this may cause pain and damage at the injection site.
Step 3
Carefully remove the cap from the hypodermic needle. Do not touch it and be careful not to stick yourself with the tip of the needle. Hold the syringe upright and flick it with your finger to make any air bubbles go to the top. Holding the syringe upright, push the plunger slowly up to expel air and excess fluid from the syringe so that the syringe plunger stops at the 0.4 mL mark.
Place the syringe on the carton so that the needle stays on top of the package and does not touch other surfaces.
Select an injection site
Select an injection site on the upper thighs or abdomen, at least 5 cm from the navel. If the injection is performed by a healthcare professional, other sites for subcutaneous injections may be selected. The drug should not be injected into moles, scars, lesions or indurations, areas of redness, skin hypersensitivity reactions.
It is recommended to change the injection site regularly. The new injection site should be at least 2.5 cm from the previous one. You can alternate injection sites between the thighs and abdomen.
Perform the injection
Clean the skin of the selected injection site with a new sterile alcohol wipe. Allow the injection site to dry and do not touch it prior to injection.
Gently squeeze the skin around the injection site with your non-dominant hand (for example, if you are right-handed, use your left hand) and hold it firmly.
Hold the syringe in your dominant hand over the raised area of skin at a 90 degree angle. Insert the needle into the skin with a quick, smooth thrusting motion. If there is a low amount of subcutaneous fat on the abdomen, a 45-degree angle may be used..
Do not move the needle relative to the tissue and push the plunger down slowly until the entire volume of the drug from the syringe is injected under the skin. The plunger should reach the bottom of the syringe. Wait a few seconds before removing the needle. Pull the needle out of the skin at the same angle at which it was inserted. There may be slight bleeding at the injection site. If necessary, place a sterile wipe on the injection site.
Place the syringe on the carton so that the needle stays on top of the package and does not touch other surfaces.
Select an injection site
Select an injection site on the upper thighs or abdomen, at least 5 cm from the navel. If the injection is performed by a healthcare professional, other sites for subcutaneous injections may be selected. The drug should not be injected into moles, scars, lesions or indurations, areas of redness, skin hypersensitivity reactions.
It is recommended to change the injection site regularly. The new injection site should be at least 2.5 cm from the previous one. You can alternate injection sites between the thighs and abdomen.
Perform the injection
Clean the skin of the selected injection site with a new sterile alcohol wipe. Allow the injection site to dry and do not touch it prior to injection.
Gently squeeze the skin around the injection site with your non-dominant hand (for example, if you are right-handed, use your left hand) and hold it firmly.
Hold the syringe in your dominant hand over the raised area of skin at a 90 degree angle. Insert the needle into the skin with a quick, smooth thrusting motion. If there is a low amount of subcutaneous fat on the abdomen, a 45-degree angle may be used..
Do not move the needle relative to the tissue and push the plunger down slowly until the entire volume of the drug from the syringe is injected under the skin. The plunger should reach the bottom of the syringe. Wait a few seconds before removing the needle. Pull the needle out of the skin at the same angle at which it was inserted. There may be slight bleeding at the injection site. If necessary, place a sterile wipe on the injection site.
Remember!
Dispose of used syringes in the sharps container immediately after injection. When the container is full, close it carefully and tightly and discard it in a trash can.
Always use a new syringe, do not reuse syringes.
Dispose of used syringes in the sharps container immediately after injection. When the container is full, close it carefully and tightly and discard it in a trash can.
Always use a new syringe, do not reuse syringes.
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OLOKIZUMAB
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Josef S. Smolen, Eugen Feist, Saeed Fatenejad, Sergey A. Grishin, Elena V. Korneva, Evgeniy L. Nasonov, Mikhail Y. Samsonov, and Roy M. Fleischmann. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med . 2022; 387:715-726. DOI: 10.1056/NEJMoa2201302
Mahmoud MA.Olokizumab’s effectiveness and safety in patients with rheumatoid arthritis: A systematic review and meta-analysis of randomized controlled trials.Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. &2022 Elsevier Inc.DOI: org/10.1016/j.jocd.2022.12.003
Mikhaylenko, D.S., Kuznetsova, E.B., Musatova, V.V., Bure, I.V., Deryagina, T.A., Alekseeva, E.A., Tarasov, V.V., Zamyatnin, A.A., Jr., Nemtsova, M.V.Genetic and Clinical Factors Associated with Olokizumab Treatment in Russian Patients with Rheumatoid Arthritis.J.Pers. Med. 2022, 12, 641. DOI: rg/10.3390/jpm12040641
Eugen Feist and Evgeny Nasonov.Interleukin 6 Inhibition in Rheumatoid Arthritis: Highlight on Olokizumab.touchREVIEWS in RMD.2023;2(1).Online published
Young Ho Lee, Gwan Gyu Song.Comparison of the efficacy and safety of tocilizumab, sarilumab, and olokizumab in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials.Zeitschrift für Rheumatologie.2023 Published online.DOI: org/10.1007/s00393-022-01315-0
Young Ho Lee · Gwan Gyu Song.Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials.Zeitschrift für Rheumatologie.Published online 2 June, 2023.DOI: org/10.1007/s00393-023-01367-w
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- Virgin Islands include British Virgin Islands and United States Virgin Islands
Instructions for medical use of the medicinal product Artlegia, registration certificate LP- 006218 dated 21.05.2020, updated on 19.02.2024.
- Instructions for the medical use of the drug Artlegia, registration certificate LP- 006218 dated 21.05.2020, updated on 19.02.2024.
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Clinical Guidelines 2021 Rheumatoid Arthritis. www.cr.minzdrav.gov.ru/... Accessed March 18, 2022.
Clinical Guidelines 2021 Rheumatoid Arthritis. www.cr.minzdrav.gov.ru/... Accessed March 18, 2022.
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- Clinical Guidelines 2021 Rheumatoid Arthritis. www.cr.minzdrav.gov.ru/... Accessed March 18, 2022.
- Nasonov EL, Olyunin YuA, Lila AM. Rheumatoid arthritis: the problems of remission and therapy resistance. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2018;56(3):363-271 (In Russ.) doi: 10.14412/1995-4484-2018-263-271
- Clinical Guidelines 2021 Rheumatoid Arthritis. www.cr.minzdrav.gov.ru/... Accessed March 18, 2022.
- Nasonov EL, Olyunin YuA, Lila AM. Rheumatoid arthritis: the problems of remission and therapy resistance. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2018;56(3):363-271 (In Russ.) doi: 10.14412/1995-4484-2018-263-271
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Instructions for medical use of the medicinal product Artlegia, registration certificate LP- 006218 dated 21.05.2020, updated on 19.02.2024.
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- Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
- Electronic resource: https://clinicaltrials.gov/... Access date 19.02.2024.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Electronic resource: https://clinicaltrials.gov/... Access date 19.02.2024.
- Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
- Electronic resource: https://clinicaltrials.gov/.... Access date 19.02.2024.
- Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
- Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Electronic resource: https://clinicaltrials.gov/.... Access date 19.02.2024.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Electronic resource: https://clinicaltrials.gov/.... Access date 19.02.2024.
- Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3.)
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.
- Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, Samsonov M, Smolen JS, Fleischmann RM. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Dec;81(12):1661-1668. doi: 10.1136/ard-2022-222630. Epub 2022 Sep 15.
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Electronic resource: https://clinicaltrials.gov/.... Access date 19.02.2024.
Electronic resource: https://clinicaltrials.gov/.... Access date 19.02.2024.
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- Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, Maslyanskiy AL, Samsonov M, Stoilov R, Zonova EV, Genovese M. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022 Apr;81(4):469-479. doi: 10.1136/annrheumdis-2021-219876. Epub 2021 Aug 3. (
- Electronic resource: https://clinicaltrials.gov/... . Access date 19.02.2024.
- Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, Samsonov MY, Fleischmann RM; CREDO2 Group. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2022 Aug 25;387(8):715-726. doi: 10.1056/NEJMoa2201302.