Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

Netakimab (NTK) is a humanized anti-interleukin-17A monoclonal antibody. To date, the drug has been approved to treat ankylosing spondylitis (AS), psoriatic arthritis, and plaque psoriasis. The paper gives the data obtained during 52-week follow-up of AS patients in the phase III ASTERA study.Objective: to study the efficacy and safety of NTK when used long in patients with active AS.Patients and methods. The investigation enrolled 228 patients with active AS, in whom nonsteroidal anti-inflammatory drugs or biological agents were ineffective. The patients were randomized in a 1:1 ratio to receive NTK 120 mg or placebo. The drug was administered subcutaneously at weeks 0, 1, 2, and then once every 2 weeks. Patients who received placebo and achieved a 20% improvement according to the ASAS criteria (ASAS20) were excluded from the study at week 16. At this week, patients who took placebo and did not achieve an ASAS20 response were switched to subcutaneous NTK at 120 mg dose once every two weeks. The follow-up period was 52 weeks.Results and discussion. Patients with active AS who received NTK were more likely to respond to treatment than those who took placebo. The proportion of people who achieved 40% improvement (ASAS40) during treatment with NTK increased throughout the follow-up period and amounted to 80.7% at week 52. Positive changes were achieved in all used clinical and laboratory parameters of AS activity. There was also a decrease in inflammatory changes, as shown by magnetic resonance imaging (MRI). The adverse events (AEs) were mainly laboratory abnormalities and upper respiratory tract infections. Treatment-related AEs were recorded in no more than one third of patients and they were mild to moderate. Severe AEs were singular.Conclusion. Response to NTK therapy generates in the first weeks of drug use and increases throughout a year. The safety profile of NTK when used long is generally favorable.

BackgroundEfficacy and safety of netakimab (NTK), a humanized anti-IL17A antibody, was established in phase 2 clinical trials in patients (pts) with radiographic axial spondyloarthritis (r-axSpA)1 and psoriasis2.ObjectivesThe abstract presents 16-week data from ongoing ASTERA study (NCT03447704) in pts with active r-axSpA.MethodsASTERA is a phase 3 international double-blind placebo (PBO)-controlled study. 228 adult pts with r-axSpA, active (BASDAI ≥ 4) despite the standard NSAIDs, were randomly assigned (1:1) to receive 120 mg NTK or PBO SC at Week (Wk) 0,1,2 and then q2w through Wk 16. After Wk 16 all pts will start to receive NTK up to Wk 52. Primary endpoint was ASAS40 rate at Wk 16.ResultsThe mean age at baseline was 39.14±9.9 years, the mean symptoms duration was 4.3±4.5 years. 76.8% of pts were naïve to biological treatment. At Wk 16 ASAS40 rate was higher in NTK arm compared to PBO: 40.35% versus (vs.) 2.63% pts (95% CI for the difference in ASAS40 rate was [27.37%; 48.07%] (p<0.0001, Figure 1). Efficacy of NTK was also proved by comparison of secondary endpoints (Figure 2); improvement in BASDAI, MASES, BASFI became significant from Wk 4 and remained during the study (no data presented). Most reported adverse events (AE) and treatment-related AEs (TRAE) were mild/moderate (Table 1). The most frequent AEs were anemia, neutropenia, ALT increase. One serious AE (SAE), not related to the treatment (bone fracture), was reported in NTK arm.ConclusionNTK at a dose 120 mg is well-tolerated drug with favorable safety profile that leads to decline in r-axSpA activity, function improvement and axial mobility in 16 Wks.References[1] Mazurov V, et al. Ann Rheum Dis 2018;77:A64. 2Samtsov A, et al. Vestn Dermatol Venerol 2017;0(5):52-63.Table 1Safety data % of patients with NTK (n = 114) PBO (n = 114) p-value AE/SAE 33.3% (38) 25.4% (29)0.245TRAE17.5% (20)14.0% (16)0.586SAE0.9% (1)01.0Grade 3-4 AEs2.6% (3)3.5% (4)1.0Grade 3-4 TRAEs1.8% (2)1.8% (2)1.0Local reactions1.8% (2)0.9% (1)1.0Figure 1Figure 2Disclosure of InterestsInna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: paiment from Pfizer, Novartis, Abbvie, Biocad, Selgene, MSD, Sanofy does not exceed 10 000 euros, V Mazurov Grant/research support from: JSC BIOCAD, Shandor Erdes Grant/research support from: JSC BIOCAD, Speakers bureau: JSC BIOCAD, Tatiana Dubinina: None declared, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Elena Ilivanova Grant/research support from: JSC BIOCAD, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Aleksander Kastanayan Grant/research support from: JSC BIOCAD, Tatyana Povarova Grant/research support from: JSC BIOCAD, Elena Zhugrova Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Pavel Shesternya Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Olga Antipova Grant/research support from: JSC BIOCAD, Elena Smolyarchuk Grant/research support from: JSC BIOCAD, Oksana Tciupa Grant/research suppo...

Netakimab (NTK) is a humanized monoclonal antibody targeting interleukin-17A.Objective. The main objective of BCD-085-5/ASTERA study was to prove superiority of NTK over placebo and assess its’ safety in patients with active AS.Subjects and methods. BCD-085-5/ASTERA was a double-blind, multicenter, randomized, placebo-controlled, phase III study, which included 228 adult patients with active AS, persisting despite active treatment with NSAIDs. AS was considered active at BASDAI score ≥ 4.0. Patients were blindly randomized (1:1) to receive subcutaneous injections of NTK (120 mg) or placebo at weeks 0, 1, 2 and then every other week up to week 14. Starting from week 16 all patients from NTK group and patients from placebo group not achieving ASAS20 were switched to open label 120 mg NTK s/c once every two weeks. The total duration of treatment with NTK was 3 years.Results. Higher proportion of patients had ASAS40 response at week 16 (primary endpoint) in NTK arm compared to placebo (40,4 vs 2,6%, р <0,0001, 95% CI [27,4%; 48,1%]). Spinal pain subsided and laboratory inflammation markers decreased within one week after the first NTK injection. NTK safety profile was comparable to that of placebo. The most common for NTK adverse events were neutropenia (7,0%) and ALT increase (6,1%).Conclusion. Subcutaneous NTK at 120 mg dose demonstrated superior efficacy vs placebo, with fast onset of response and favorable safety profile when used in patients with ankylosing spondylitis.

О р и г и н а л ь н ы е и с с л е д о в а н и я 1 ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия; 2 Кафедра пропедевтики внутренних болезней ГБОУ ВПО «Кемеровская государственная медицинская академия» Минздрава России, Кемерово, Россия; 3 Кафедра пропедевтики ГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России,