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The criteria for diagnosis and classification of spondyloarthritides (SpAs) have undergone significant changes over the past 10 years. The emergence of new diagnostic methods and availability of new information on the prognosis of the disease outcome made it possible to distinguish a separate group of SpAs—axial SpA. Axial SpA is distinguished as a separate disease due to its high social significance, and special mechanisms of its development. The development of medicinal products for the treatment of axial SpA has some specific features, which requires preparation of specific recommendations for conducting clinical trials of such products. The aim of the study was to elaborate a methodological approach to clinical research and evaluation of efficacy and safety of medicinal products for systemic treatment of axial SpA. The study took into account the requirements/recommendations of the European Medicines Agency for planning clinical trials of medicinal products for the treatment of axial SpA, in order to streamline evaluation of national and foreign clinical trial results. The paper identifies the main stages of clinical trials, and proposes criteria for assessing product efficacy at each stage. It defines methods and tools for assessing clinical trial endpoints, which are necessary for evaluation of treatment effects. The paper describes specific aspects of clinical trial designs and their duration, and identifies the objectives of exploratory and confirmatory clinical trials. It also reviews treatment goals and treatment outcome evaluation. The study results could be used in elaboration of recommendations for clinical research of new medicinal products for axial SpA.

The currently used methods for evaluating the progression of structural damages in early axial spondyloarthritis (axSpA) are little suitable to real practice since they require specially trained radiologists and increase a patient's exposure to radiation due to the need for radiography of three regions of the axial skeleton. In addition, the first radiological bone changes in the sacroiliac joints (SIJ) appear only many years after the onset of the disease, the overlying spine areas are involved in the pathological process. Objective: to develop a method for evaluating the radiographic progression of sacroiliitis (SI) in early axSpA for real clinical practice. Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort (ESAC) formed at the V.A. Nasonova Research Institute of Rheumatology. The current ESAC comprised 164 patients; the analysis included 68 patients who had been followed up for at least 2 years and had plain pelvic bone films at the inclusion in the cohort and at 2-year follow-up. To evaluate disease progression, the investigators used the sum of radiographic SI stages in the left and right SIJs (the summary stage of radiographic SI (ssrSI), which was calculated at baseline and at 2-year follow-up. A formula for determining the rate of radiographic progression was derived. Results and discussion. At baseline and at 2-year follow-up, the median ssrSI difference (ΔssrSI) in 68 patients was 0 [0; 1.0]. During the study period, almost 60% of the patients had no progression of ssrSI, i.e. ΔssrSI was 0 in these patients, 1 and 2 scores in 12 (18%) and 13 (19%) patients, respectively, and there were singly cases, in which this figure was equal to 3, 4 and 7. The mean value of ssrSI was 3.5±1.6 at baseline and increased by 0.8, reaching 4.3±1.5 at 2 years (p = 0.006). Before included into the investigation, the patients had a progression rate of 1.75 during 1 year, which decreased to 0.4 per year in the active follow-up period. At the time of inclusion in the study, 40 (58.8%) of the 68 patients had ankylosing spondylitis (AS), and at 2 years their number increased to 51 (75.0%); i.e. 11 (39%) patients were observed to have progression of non-radiographic axSpA to AS. Conclusion. The proposed procedure to calculate ssrSI is easily feasible in real practice; it fails to lead to additional radiation exposure, is economically feasible, and allows one to monitor the rate of progression of axSpA in the early stage of the disease.

Objective: to compare the impact of continuous or on-demand use of nonsteroidal anti-inflammatory drugs (NSAIDs) on the activity and radiographic progression of early axial spondyloarthritis (axSpA).Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort who met the 2009 Assessment of Spondyloarthritis International Society (ASAS) criteria for axSpA. This analysis included 68 patients who had been followed up for at least 24 months. The mean age at the time of inclusion in the investigation was 28.5±5.8 years; the mean disease duration was 24.1±15.4 months; 63 (92.6%) patients were HLA-B27-positive. The patients were divided into two groups: 1) 35 patients used NSAIDs at maximum therapeutic doses continuously during the follow-up period; 2) 33 patients received these drugs on-demand, depending on the presence and severity of back pain.Results and discussion. After 2-year follow-up, the median stage of radiographic sacroiliitis (SI) in Group 1 was unchanged and remained equal to 4; that in Group 2 in this period significantly increased from 3 to 4 scores (p < 0.05). At baseline, the patient groups did not differ in C-reactive protein (CRP) levels, the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), and the Bath Ankylosing Spondylitis Functional Index (BASFI); however, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was higher in Group 1 (p < 0.05). The number of patients with active SI, as evidenced by magnetic resonance imaging (MRI), and the degree of its severity did not differ significantly between groups. After 2 years, all the patients retained low disease activity according to ASDAS-CRP, BASDAI, and CRP levels; and these measures did not differ significantly between groups either; the BASFI became higher in Group 1. MRI findings indicated that the number of patients with active SI decreased, but no differences were found between the groups.Conclusion. In patients with early axSpA, the continuous intake of NSAIDs can slow radiographic progression to a greater extent than their on-demand use.