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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.

Ревматические заболевания (РЗ) занимают значительное место в структуре общей заболеваемости населения во всех странах мира, в том числе и в России. Известно, что патология опорно-двигательного аппарата стоит в ряду основных причин временной утраты трудоспособности, занимая второе-третье место по дням и случаям нетрудоспособности среди всех регистрируемых официальной статистикой классов болезней, а доля общей инвалидности в связи с РЗ среди всех инвалидов составляет около 10% [1]. Одним из действенных средств привлечения

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BackgroundCurrently a number of risk factors (RF) are considered to be responsible for radiological progression of knee osteoarthritis (OA), nevertheless key predictors of OA progression have not yet been established.ObjectivesTo identify RF predicting radiological progression of knee joint osteoarthritis (OA) in a 5 year multicenter prospective study.MethodsThis study of RF predicting knee OA progression was the first with multicenter prospective design ever conducted in Russia. The study included 344 female patients 40–75 y.o with primary stage I-III knee OA (ACR criteria) from 6 centres. Radiological stage was identified by Kellgren J.- Lawrence J. grading scale. The follow up (FUP) was 5 years. Individual patients’ files described 90 parameters. Instrumental diagnostic methods included plain radiography of knee joints, dual energy X-ray absorptiometry (DEXA) of lumbar spine L1–4, femoral neck and subchondral tibia, ultrasound (US) and MRI examination of knee joints. OA progression was verified based on evolution of radiological stage. At baseline 24 pts (7%) had stage I OA, 227 (66%) – stage II, and 93 (27%) – stage III. Discriminant analysis was applied to verify most reliable RF predicting radiological progression.ResultsRadiological progression was documented in 45% participants during 5 year FUP. The groups with and without progression were comparable in terms of age and disease duration (»<0,05). Pts who progressed suffered more intensive knee pain – 68(52–72) vs 41(30–63) mm, » <0,01, had higher body weight – 82(77–93) vs 72(65–81) kg, » <0,01, had higher rates of knee synovitis (US) 44% vs 26%, »=0,03, (RR=1,67, 95% CI 1,07–2,59) and mid-tibia bone marrow oedema – 60% vs 28%, » <0,01 (RR=2,12, 95% CI 1,34–3,35). The discriminant analysis showed that knee pain, excessive body weight, synovitis and mid-tibia bone marrow oedema (MRI) can be considered as predictors of OA radiological progression. A model capable of predicting OA course in an individual patient with high 88% accuracy, 87.7% sensitivity and 70% specificity has been developed based on identified RF and their coefficients. Area under the ROC-curve 0, 921 (95% CI 0,875–0,966).ConclusionsKnee pain, excessive body weight, synovitis and bone marrow oedema should be considered as key RF predicting knee OA radiological progression.Disclosure of InterestNone declared