The efficiency of glucocorticoid (GC) therapy for systemic lupus erythematosus (SLE) is beyond question and is confirmed by the experience gained over many decades of their use. However, there are many problems with prolonged GC use, even in its low and medium doses. In particular, the development of GC-associated irreversible organ damages significantly worsens prognosis and causes a decrease in quality of life and social adaptation and a substantial increase in treatment costs. On the other hand, the current capabilities of early diagnosis, pathogenetic therapy, and monitoring in many patients with SLE allow for maintaining low disease activity and remission, the conditions in which the feasibility of further GC treatment can and should be decided. The paper gives the data available in the literature and the authors’ own studies on the possibility and prospects of GC withdrawal in SLE patients in a stage of low disease activity and remission.

Rituximab (RTM), a monoclonal antibody against CD20+ receptors on the membrane of B-cells, is becoming increasingly important for the induction and maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (ANCA-SV). The challenge facing us is to optimize its efficacy, while limiting adverse events (AEs).

Objective: to evaluate the efficacy and safety of RTM used for the induction and maintenance of remission in ANCA-SV on the basis of 10-year single-center experience.

Patients and methods. The paper presents the authors’ own 10-year experience with RTM used for the induction and maintenance of remission in 103 patients with ANCA-SV, including granulomatosis with polyangiitis (GPA) (n=58), microscopic polyangiitis (MPA) (n=35), ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA) (n=4), and ANCA-negative EGPA (n=6). The duration of a follow-up after initiation of RTM treatment was more than a year (with the exception of death cases) and averaged 25 to 58 months in different ANCA-SV groups. The patients were monitored every 3 months. The intervals between repeated cycles were dependent on the time course of changes in clinical and laboratory parameters. The mean cumulative RTM dose exceeded 3 g; 75% of patients received repeated cycles of RMT usually at a cumulative dose of 0.5–1.0 g at a 4–12-month interval.

Results and discussion. Repeated RTM cycles for ANCA-SV were highly effective; the clinical response rate was 97%, while 90–93% of patients with different types of ANCA-SV achieved complete clinical response. Despite the fact that the examined population included a high proportion of patients with a severe or refractory course of the disease; ANCA-SV patients showed 10% mortality rates during the entire follow-up period. Anti-B-cell therapy with RTM is of great importance in obtaining long-term optimal results, making it possible to improve ANCA-SV control and to minimize the cumulative dose of glucocorticoids. Since in ANCA-SV, the use of repeated cycles of RTM, including that at a reduced dose of 0.5 g, contributes to the higher efficiency of treatment and to the lower risk of relapse, it is advisable to perform long-term (≥2 years) RTM therapy, by controlling the parameters of clinical and immunological activities and the levels of circulating CD20+ B cells and serum immunoglobulins, deficiency of which can potentially increase the risk of infectious AEs. When planning RTM therapy, it is necessary to consider the specific features of the safety profile for individual nosological entities and to make a careful appropriate monitoring of ANCA-SV patients receiving RTM. The risk of late-onset neutropenia was highest in patients with all types of ANCA-SV (3–10%). Infections in patients with GPA and MPA constitute a substantial proportion (10–11%) in serious AEs. Management of EGPA patients requires alertness to the risk of infusion-related reactions, primarily bronchospasm.

Conclusion. There is a need for further investigation of an anti-B-cell therapy strategy, including the efficacy and safety of RTM in ANCA-SV and for clarification of indications and optimal RTM treatment regimens. 

Objective: to determine body composition (BC) in women with systemic lupus erythematosus (SLE), by using bioimpedance analysis.

Patients and methods. The investigation enrolled 12 women with a reliable diagnosis of SLE, who were followed up at the Clinic of the V.A. Nasonova Research Institute of Rheumatology. Their median age was 46.5 [38.5; 54.7] years. All the patients underwent estimation of waist circumference (WC) and body mass index (BMI). BC was analyzed using an InBody 770 multi-frequency bioimpedance analyzer (Biospace Co. Ltd, South Korea) at the Clinical Nutrition Clinic, Federal Research Institute of Nutrition and Biotechnology.

Results and discussion. BMI corresponding to overweight or obesity was observed in 67% of patients; abdominal obesity (AO) was seen in 83%. BC study showed that in most patients, adipose tissue mass was greater than the normal values (75%), lean body mass, skeletal muscle mass, and the amount of body water were within normal limits (83%), and the basal metabolic rate was reduced (67%). There were positive correlations between the percentage of adipose tissue and BMI (r=0.9; p<0.01), WC (r=0.7; p<0.01), C-reactive protein (CRP) levels (r=0.6; p<0.05), and complement C3 concentrations (r=0.9; p<0.01). Similar results were obtained when assessing the relationship between visceral fat area and BMI (r=0.9; p<0.01), WC (r=0.78; p<0.01), CRP (r=0.6; p<0.05), complement component C3 (r=0.8; p<0.01). There was an inverse correlation between visceral fat area and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (r=-0.6; p<0.05).

Conclusion. Most women with SLE have AO, increased adipose tissue mass, normal lean body mass, and decreased basal metabolism. There is a direct correlation of visceral fat content and inflammatory markers (CRP, complement component C3) and an inverse correlation of those with the SLEDAI-2K. 

Systemic lupus erythematosus (SLE) is characterized by a variability in clinical manifestations and laboratory abnormalities, which creates objective diagnostic difficulties.

Objective: to investigate clinical and laboratory parameters in patients with definite and probable SLE.

Patients and methods. The investigation enrolled 94 patients, 38 of whom were diagnosed with probable SLE. All the patients underwent immunological examination and unaffected skin biopsies, followed by an immunohistochemical study, the so-called lupus strip test (LST).

Results and discussion. The group of patients with definite SLE showed a direct correlation between positive LST and disease activity (r=0.6), acute skin lesion (r=0.42), and elevated anti-double-stranded DNA antibody concentrations (r=0.37), and their inverse correlation with dry syndrome (r=-0.44). In patients with probable SLE, deposition of immunoreactants in the unaffected skin was detected in almost half of the cases, despite lower disease activity and specific antibody deficiency. Thus, LST that is quite easy to use and interpret its results can be used as an additional criterion for the differential diagnosis of SLE, especially in its early stages. 

Objective: to analyze the provision of medical, including rheumatology, care in Kazakhstan, to study the incidence of systemic lupus erythematosus (SLE), and to develop a registry of patients with this condition.

Material and methods. The investigators analyzed the guidelines for the organization of medical, including rheumatology, care in the republic and the official statistical materials of the Ministry of Health of the Republic of Kazakhstan in the period 2012 to 2017. Articles were searched to select activity indices, organ damages and to assess the quality of life and treatment programs in order to create a registry of patients with SLE.

Results and discussion. The paper presents the basic principles of providing medical, including rheumatology, care in the republic. It gives data on the issues of providing SLE patients with medicines in outpatient and inpatient settings. It also analyzes trends in the incidence of SLE in the population of Kazakhstan in 2012 to 2017. There were 4,448 SLE patients, including 3,986 women; a comparative analysis of indicators demonstrated a 62.8% increase in the incidence of SLE from 2012 to 2017. The purpose and objectives of the registry of patients with SLE were substantiated.

Conclusion. An analysis of morbidity rates suggests that SLE remains to be significant in the republic. The incidence of SLE has been noted to increase in the period from 2012 to 2017; there is a female preponderance (89.6%). The application of the SLE registry in clinical practice will be able to improve the diagnosis of the disease in the early stage and to prevent possible complications. 

Objective: to study and analyze the clinical and laboratory manifestations, course, and outcome of systemic lupus erythematosus (SLE) in patients living in Kyrgyzstan.

Patients and methods. The prospective study included 150 young patients aged 34 [26, 44] years in a Kyrgyz cohort (KC) with SLE, the disease of which was 3.0 [0.7; 10] years. All clinical, laboratory, and instrumental data of patients, health-related quality of life (HRQOL) indicators, and treatment regimens were recorded in the international research base, such as British Lupus Integrated Prospective System (BLIPS). SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). At the end of the observation, the investigators assessed the following indicators: the number of exacerbations of SLE by the SELENA Flare Index (SFI); the onset of complete or drug-induced remission; the number of deaths; and the development of irreversible organ damages (IOD) according to the damage index (DI).

Results and discussion. When seeing the physician for the first time, the KC included more patients with high (n=61 (40.66%)) and very high (n=40 (26.67%)) disease activity. Most (n=60 (40%)) patients were observed to have a subacute type of the course of the disease. At the first visit, the most common manifestations of SLE were damages to the skin (n=99 (72.67%)), serous membranes (n=91 (60.67%)), and lupus nephritis (n=79 (52.67%)). IODs were identified in 15.33% of the patients and were absent in 84.67%. IODs were more often due to the administration of glucocorticoids (GCs) in 43.48% of cases. However, GC therapy was not a predictor of organ damages (relative risk, 0.91; p>0.05). In the KC, the significant predictors of adverse outcomes were old-age onset SLE and its high activity, acute course, and frequent exacerbations.

Conclusion. The KC patients had high and very high clinical and laboratory activities (40.6 and 26.6%, respectively), mainly those of acute and subacute SLE (32 and 40%, respectively), obvious immunological disorders. There was a preponderance of damages to the skin (73%), serous membranes (61%), and kidney (53%) among the clinical manifestations of SLE. IODs were found in 15.33% of patients at their study inclusion. These were more frequently represented by GC-induced changes. However, the ongoing GC therapy in the KC patients was not a predictor of organ damages. The significant predictors of an adverse outcome in our patients were old-age onset SLE and its high activity, acute course, and frequent exacerbations. 

In anti-U1-ribonucleoprotein (anti-U1-RNP) antibody positive patients with systemic scleroderma (SSD), the clinical picture and course of the disease have specific features: there is a preponderance of its limited form; inflammatory damage to the joints and muscles comes to the fore; and cutaneous manifestations are mild. Moreover, a high frequency (68%) of interstitial lung disease is found. At the same time, the autoimmune profile in this group has been little studied.

Objective: to investigate the level of major autoantibodies (autoAbs) in anti-U1RNP antibody positive patients with SSD and to compare the frequency of the autoAbs in this group and in the groups of patients with SSD phenotypes associated with anti-centromere antibodies (ACA) and anti-topoisomerase I (anti-Scl70) antibodies.

Patients and methods. The investigation enrolled a total of 144 patients meeting the 2013 ACR/EULAR SSD classification criteria. Forty-four anti-U1RNP antibody positive patients were found to have autoAbs, rheumatoid factor (RF), anti-cyclic citrullinated peptide (ACCP), anti-Ro, anti-La, anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-cardiolipin (aCL), anti-histidyl tRNA synthetase (anti-Jo1), anti-Scl70, and anti-RNA polymerase III (anti-RNAP-III) antibodies, and ACA in two points. The study group (anti-U1RNP antibody positive patients with SSD) and the comparison groups (anti-Scl70 and ACA positive patients) were comparatively analyzed.

Results and discussion. Anti-U1RNP antibody positive patients with SSD were commonly observed to have overlaps (34%) with rheumatoid arthritis and systemic lupus erythematosus, as well as concurrence with Sjögren’s syndrome (SS) (32.5%). The study group was found to have frequently RF (27%), anti-Ro (41%), anti-dsDNA (50%) antibodies, rarely anti-Sm (9%), ACCP (9%), anti-La (7%), ACA (11%), anti-Scl70 (9%), and aCL (2%) antibodies. Anti-Jo1 and anti-RNAP-III antibodies were not detected in any patient. SSD patients who were highly positive for anti-U1RNP antibodies (more than 2 upper limits of the reference range) significantly more frequently exhibited RF, anti-Ro and anti-dsDNA antibodies (p<0.01). Over time, anti-U1RNP antibodies detected at the onset of the disease persisted in 75% of patients. autoAbs were observed to disappear in patients with a low baseline titer of anti-U1RNP antibodies. Re-examination demonstrated that the detection rate of other autoAbs remained high in the group of patients who were highly positive for anti-U1RNP antibodies. Comparison of the three groups showed that the specific feature of the study group was the more frequent presence of other autoAbs, among which anti-Ro antibodies were most important. Their presence was associated with SS.

Conclusion. In addition to clinical features, patients with SSD and anti-U1RNP antibody overproduction differ from those with major SSD phenotypes by the more frequent presence of other autoAbs. Persons who are highly positive for anti-U1RNP show the steady-state elevated levels of RF, anti-Ro and anti-dsDNA antibodies and the rare detection of SSD-specific autoAbs (ACA, anti-Scl70 and anti-RNAP-III). 

Objective: to study the clinical and laboratory features of lobular panniculitides (LPn) on a cohort of patients referred to the rheumatology center.

Patients and methods. The investigation enrolled 687 patients (613 women and 74 men; mean age, 39.7±11.3 and 41.2±12.5 years, respectively) with panniculitis (Pn) who had received outpatient and/or inpatient treatment for diagnosed erythema nodosum or panniculitis at the V.A. Nasonova Research Institute of Rheumatology in 2007–2017.

Results and discussion. By applying the diagnostic algorithm developed by the authors and the existing classification of Pn, the investigators diagnosed septal Pn in 430 (62.6%) patients and LPn in 249 (36.2%). The latter was associated with rheumatic diseases (RDs) in 97 (39%) patients. Most (70%) cases were patients with idiopathic LPn (ILPn), which, according to the 10th edition of the International Classification of Diseases, belongs to a group of systemic connective tissue disorders (M35.6), as well as those with systemic lupus erythematosus (SLE) (11.45%), dermatomyositis (DM) (9.37%), and rheumatoid arthritis (7%). This group showed a preponderance of females (the ratio of males to females was 1:7) with the chronic course of the disease mainly in ILPn. The clinical picture corresponded to four types of LPn, which may be of diagnostic and prognostic value in RDs.

Conclusion. This investigation confirmed the relevance of studying LPn in RDs because of its negative impact on the course, severity and therapeutic efficiency of the underlying disease. 

Objective: to study bone mineral density (BMD) in elderly and senile women with knee and hip osteoarthritis (OA).

Patients and methods. The investigation enrolled 124 women (mean age, 73.3±8.46 years) diagnosed with OA meeting the ACR diagnostic criteria. Lumbar spine (LI-IV) and femoral neck BMD values were determined; knee and hip X-ray in the frontal projection was carried out to assess the radiographic stage according to the Kellgren and Lawrence classification.

Results and discussion. The overall incidence of osteoporosis (OP) and ostopenia in the study cohort was 28 and 41%, respectively. OP was diagnosed in 20% of women aged 60–74 years and in 38% of those aged 75–90 years (p<0.05); osteopenia was in 41 and 42%, respectively (p>0.05). In the age groups of 65–74 years and ≥75 years, women with stage III–IV hip OA had a significantly higher femoral neck BMD than those with Stage I–II (p<0.05). At the same time, the later radiographic stages of hip OA were associated with lower lumbar spine BMD (p<0.05). The patients of both age groups who had Stages III and IV knee OA had a significantly higher lumbar spine BMD than those with Stage I–II OA (p<0.05). The femoral neck BMD in patients with Stages I–II and III–IV knee OA was comparable in both age groups (p>0.05).

Conclusion. The relationship between BMD and OA-related structural changes is contradictory and requires further investigation. 

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile.

Objective: to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA.

Patients and methods. 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy.

Results and discussion. No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant.

Conclusion. This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections). 

IgG4-related disease (IgG4-RD) is a rare immune-mediated fibroinflammatory disease that is characterized by the occurrence of nodules in one or more organs and proceeds in most patients with the elevated levels of IgG4 in serum and/or in the tissues of the affected organs. The majority of patients are elderly men, and the disease in most cases has a slowly progressing systemic course. The cases of isolated IgG4-related injury to the viscera, which are much less common than the systemic type of the disease, are a very difficult differential diagnosis, and biopsy of these organs is associated with technical difficulties and poses a threat to the patient's health. The paper describes just such a case. It is interesting from several points of view: firstly, a rare site (solitary pulmonary nodular lesion); secondly, clinical and laboratory features (childhood onset, no immunological abnormalities – both higher serum IgG4 levels and lower complement components).

Clinicians should remember that IgG4-RD does not always have a systemic course and characteristic serological markers. In these cases, histological verification of the diagnosis is of particular importance. If the histological pattern of a fibroinflammatory pseudotumor is identified, especially in the presence of multiple nodules, IgG4-RD should always be included in the differential diagnosis. 

The term cryoglobulinemia (CG) is used when detecting serum immunoglobulins that reversibly precipitate and form a gel at a temperature below 37 °C and dissolve when the temperature rises above 37 °C. Type I CG consists of only one isotype or a subclass of monoclonal immunoglobulins, while types II and III are classified as mixed CG (MCG) that is primarily characterized by the presence of immunoglobulins G and M. Types II and II-III MCG can result in cryoglobulinemic vasculitis (CGV) more frequently, whereas type III can lead to this condition less frequently. The presence of type I cryoglobulins is always associated with B-cell lymphoproliferative diseases. On the contrary, type II or type III MCG is more commonly associated with systemic autoimmune diseases and chronic infections. Thus, hepatitis C virus infection contributes to the development of MCG in 80–90% of cases. CGV is considered a rare disease worldwide (<5 cases per 10,000 people in the general European and North American populations). Among autoimmune diseases, primary Sjögren's syndrome (Sjögren's disease), systemic lupus erythematosus, and rheumatoid arthritis are most often associated with MCG. The pathogenetic role of cryoglobulins in inducing vasculitis is associated with both leukocyte recruitment to the vessels and deposition of immune complexes, with complement system activation and microvascular damage. The pathogenesis of MCG is associated with B-cell lymphoproliferation, autoantibody production, immunoglobulin synthesis, rheumatoid factor activity and the subsequent formation of cryoprecipitated immune complexes in conjunction with ineffective cryoglobulin clearance by monocytes and/or macrophages. This review contains updated information on the epidemiology, etiology, and pathogenesis of CG, with particular emphasis on MCG and CGV.

Sjögren's disease (SD) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands, leading to the development of their destruction and progressive functional failure. The prevalence of SD is about 5%, which makes it one of the most common autoimmune diseases. SD often has a chronic, slowly progressing course.

The paper discusses the results of international clinical trials of the efficiency of anti-B-cell therapy with rituximab (RTM) for glandular SD. It considers the impact of this therapy on various immunological, histological indicators, subjective and objective parameters of glandular function, and disease activity. Possible reasons for the discrepancy between the results of open-label clinical trials and randomized clinical trials, as well as predictors for the efficiency of RTM therapy are discussed.

It has been found that RTM used to treat SD effectively reduces B-cell activity, improves the morphological pattern in the salivary glands and some extraglandular manifestations of the disease, and diminishes dryness and weakness. Anti-B-cell drugs have a great potential to treat SD. 

Rheumatic diseases (RDs), including osteoarthritis and rheumatoid arthritis, are non-infectious slowly progressive incurable inflammatory diseases that lead to prolonged disability due to damage to the musculoskeletal system. Pain is a dominant symptom at any stage of these diseases, is directly related to joint functioning, and determines the quality of life in patients. Moreover, despite the significant successes of studying the role of inflammation and regulation of autoimmune processes, the pathogenetic mechanisms for the development and maintenance of pain in RDs are little investigated. The nociceptive mechanisms due to inflammation and/or joint structural impairment are involved in the development of rheumatic pain. In addition, the latter is also associated with impaired signaling in the nervous system and with psychological problems in patients.

At the present stage, pain treatment includes non-pharmacological interventions, as well as the use of certain pharmacological agents, in particular opioids and narcotic drugs. However, despite significant successes in the design of drugs that relieve pain, at present, a significant proportion of patients with RDs still experience pain after therapy. When designing novel drugs for the treatment of pain, it is necessary to take into account the molecular mechanisms of its development in RDs. This review considers the features of the manifestations of pain, its molecular markers and mechanisms at different stages of the disease in patients with the two most common RDs, such as rheumatoid arthritis and osteoarthritis. 

The paper presents data on the pathogenesis of systemic lupus erythematosus (SLE), and depicts various molecular mechanisms for the development of SLE and lupus-like syndromes. It describes groups of diseases, such as apoptotic defects; NETosis; interferonopathies; complement deficiency; autotolerance disorders associated with mutations in the RAG1/RAG2 genes; hereditary metabolic diseases (prolidase deficiency, deficiency of adenosine deaminase 2; lysinuric protein intolerance; and α-mannosidase deficiency). The table summarizes clinical data on most of the known lupus-like syndromes and their molecular mechanisms.

The pathogenesis of many forms of monogenic lupus-like diseases is being studied. The main sign suggesting in favor of the possible monogenic disease in a patient with SLE is its onset in infancy, especially in males. Attention should be also paid to a compromised family history, including to the marriage between close relatives, the resistance of disease to standard therapy, as well as atypical symptoms. 

Etoricoxib is one of the most popular representatives of a group of nonsteroidal anti-inflammatory drugs (NSAIDs), which is widely used in Russia and other countries of the world. It is a highly selective cyclooxygenase 2 inhibitor that has a rapid and pronounced analgesic effect, a high antiinflammatory potential, and an ability to affect the development of central sensitization, one of the central mechanisms for chronic pain. The therapeutic potential and safety of etoricoxib have been extensively tested in numerous large-scale randomized controlled trials (RCTs). It has proven to be an effective agent for relief of acute pain (including that in dental practice) and acute gouty arthritis, for long-term treatment of rheumatoid arthritis, ankylosing spondylitis (AS), and osteoarthritis (OA). A meta-analysis of a series of RCTs suggests that etoricoxib may be a more effective analgesic drug for AS and OA than other NSAIDs. Etoricoxib significantly less frequently cause gastrointestinal complications than non-selective NSAIDs. The cardiovascular risk associated with etoricoxib is not higher than that with non-selective NSAIDs such as diclofenac.

The paper presents information on the 27th Congress of the International Society on Thrombosis and Hemostasis, which was held in Melbourne (Australia) in July 2019. This congress is the world’s leading forum on thrombosis and hemostasis, as well as on the causes of bleeding and their clinical manifestations. It unites all specialists who are relevant to this problem.

The conclusion of the Expert Council presents the results of discussing the diagnosis and therapy of interstitial lung diseases in systemic scleroderma. The reason for this discussion was the emergence of new data on the use of nintedanib in this category of patients.