Selection and switching of genetically engineered biological agents in treatment of juvenile arthritis
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01.05.2018 |
Zholobova E.
Ignatova A.
Seylanova N.
Golubeva A.
Shpitonkova O.
Afonina E.
Nikolaeva M.
Chebysheva S.
Meleshkina A.
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Pediatriya - Zhurnal im G.N. Speranskogo |
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0 |
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© 2018, Pediatria Ltd.. All rights reserved. Therapy with genetically engineered biological preparations (GEBP) significantly improved the prognosis and quality of life of patients with juvenile idiopathic arthritis (JIA). However, primary or secondary in efficiency, the development of undesirable phenomena require switching to another GEBP. Objective of the research – to determine optimal GEBP preparations when selecting and switching therapy based on the analysis of prescribed GEBP in real practice, depending on the clinical version of the JIA and the presence of uveitis. Materials and methods: the study included 322 patients with JIA on GEBP therapy, observed in the Pediatric Rheumatology Department of Children's Clinical Hospital of the I.M. Sechenov First Moscow State Medical University from Jan. 1, 2015 to Dec. 31, 2017. Retrospective, continuous observational clinical study. Of 322 patients, 70 (21,74%) had systemic JIA, 155 patients (48,14%) had polyarterial seronegative for rheumatoid factor (RF–) variant of JIA, 9 patients (2,8%) – polyarticular seropositive for rheumatoid factor RF+) variant of JIA, 55 patients (17,08%) – oligoarticular (persistent and spreading) variant of JIA, 26 patients (8,07%) – enthesitis (juvenile spondylitis), 7 patients (2,17%) – psoriatic variant of JIA. Results: as the first biological preparation were prescribed: etanercept to 177 (54,97%) patients; adalimumab to 51 (15,84%); tocilizumab to 44 (13,66%); abatacept to 39 (12,11%); infliximab to 11 (3,42%) patients. Transition to the second line of biological therapy was performed in 51 patients (in 15,8% of cases), on the third line of therapy in 13 patients (in 4,04% of cases), on the fourth line in 3 patients (in 0,93% of cases). As the second-line GEBP adelimumab was prescribed in 22 cases (43,14%), tocilizumab in 13 (25,49%), etanercept in 11 (21,57%), abatacept in 5 (9,8%). GEBP inefficiency was the reason for switching to the second line in 32 cases (9,9%). Of these, secondary inefficiency in 22 cases (6,8%); primary inefficiency – in 4 (1,3%), low efficiency – in 6 (1,9%), development/exacerbation of uveitis – in 7 patients (2,2%), in 6 cases (1,9%) due to insufficient compliance, drug shortage in the community, etc. Adverse effects caused switching in 5 patients (1,6%), incl. in 4 children – infusion reactions, in one – tuberculosis. Analysis of GEBP choice depending on the disease form and the presence of uveitis, was performed in 3 groups. Group 1 (n=70) consisted of patients with systemic JIA. Group 2 (n=53) included patients with articular form of JIA and concomitant uveitis. Group 3 (n=199) included patients with articular form of JIA without concomitant uveitis. Patients with systemic JIA as the first-line GEBP tocilizumab was prescribed significantly more often – to 38 patients out of 70 (54,29±5,96%) than etanercept – to 19 patients (27,14±10,19%) (t=2, 3, p<0,05), and other drugs in total (infliximab, abatacept, adalimumab) – to 13 (18,57±10,88%) (t=2,9, p<0,05). Switching to GEBP second line in this group was performed in 20 patients (28,57%). Tocilizumab was the final choice drug (after 3 years of follow-up) at the time of samples collection in 50 patients (71,43%) with systemic JIA. In patients with articular forms of JIA and concomitant uveitis as the first-line GEBP, adalimumab was prescribed significantly more often – in 34 of 53 cases (64,15±8,23%) than other drugs (abatacept, etanercept, infliximab) in total – 19 of 53 cases (35,85±11,01%) (t=2,06, p<0,05). Adalimumab was the drug final choice at the time of sample collection for 43 (81,13%) patients with JIA and uveitis. Most patients with articular form without uveitis received etanercept as first-line GEBP, 150 of 199 (75,38±3,54%), and etanercept prescription frequency was significantly higher than that of other drugs (abatacept, adalimumab, tocilizumab, infliximab) in total – 49 of 199 (24,62±6,19%) (t=7,1, p<0,01). In this group, the switching frequency was the smallest and amounted only 8,54%. The number of patients who received etanercept at the end of the study actually remained unchanged – 148 patients (74,37%).
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Switching to a second TNF-α inhibitor in a patient with severe juvenile polyarthritis: A clinical case
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01.01.2018 |
Denisova R.
Alexeeva E.
Dvoryakovskaya T.
Soloshenko M.
Mamutova A.
Isayeva K.
Fetisova A.
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Voprosy Sovremennoi Pediatrii - Current Pediatrics |
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© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Insufficient efficacy or intolerance of the first TNF-α inhibitor in patients with juvenile idiopathic arthritis (JIA) is an indication for the appointment of a second inhibitor. Golimumab is a new TNF-α inhibitor registered for treating JIA under pediatric indications. Clinical Case Description. At an early age, the patient had an onset of polyarticular JIA. Due to the aggressive and rapidly progressive course, failure of therapy with nonsteroidal anti-inflammatory drugs, methotrexate and glucocorticosteroids for intra-articular administration, infliximab was prescribed to the patient, with a positive effect. Subsequently, the patient developed a secondary resistance to infliximab, inflammatory changes in the joints relapsed; thus, a second TNF-α inhibitor (golimumab) was prescribed. In the course of therapy, pain and signs of arthritis in the patient were reversed, and the range of motion in the affected joints increased. After one year of therapy, JIA remission was ascertained. At the same time, the child was not administered oral glucocorticosteroids. The duration of remission of the joint syndrome was 5 years. Adverse events were not serious and did not constitute a basis for drug discontinuation. Conclusion. Switching to a second TNF-α inhibitor (golimumab) was effective in a patient with a secondary resistance to the first TNF-α inhibitor.
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