Prescription Trends of Biologic DMARDs in Treating Rheumatologic Diseases: Changes of Medication Availability in COVID-19.

Biologic disease-modifying antirheumatic drugs (DMARDs) are very effective in treating rheumatic diseases with a good patient tolerance. However, high cost and individualistic approach requires dedication of the physician. Therefore, the aim of this study was to determine how the COVID-19 pandemic has affected the prescription of biologic DMARDs in rheumatology at the University Hospital of Split. The data collection was conducted through an archive search in the Outpatient Clinic for Rheumatology in the University Hospital of Split, Split, Croatia. The search included the period before and after the start of the COVID-19 pandemic in Croatia (31 March 2020). Collected data included age, sex, ICD-10 code of diagnosis, generic and brand name of the prescribed drug, date of therapy initiation, and medication administration route. In the pre-COVID-19 period, 209 patients were processed, while in the COVID-19 period, 185 patients were processed (11.5% fewer). During pre-COVID-19, 231 biologic medications were prescribed, while during COVID-19, 204. During COVID-19, IL-6 inhibitors were less prescribed (48 (21%) vs. 21 (10%) prescriptions, p = 0.003), while IL-17A inhibitors were more prescribed (39 (17%) vs. 61 (30%) prescriptions, p = 0.001). In ankylosing spondylitis (AS), adalimumab was prescribed more during pre-COVID-19 (25 vs. 15 patients, p = 0.010), while ixekizumab was prescribed less (1 vs. 10 patients, p = 0.009). In rheumatoid arthritis, tocilizumab was prescribed more in the pre-COVID-19 period (34 vs. 10 patients, p = 0.012). Overall, the prescription trends of biologic DMARDs for rheumatologic diseases did not vary significantly in the University Hospital of Split, Croatia. Tocilizumab was prescribed less during COVID-19 due to shortages, while ixekizumab was more prescribed during COVID-19 due to an increase in psoriatic arthritis patients processed and due to being approved for treating AS.

The occurrence of sacroiliitis in HLA-B*35-positive patients with undifferentiated spondyloarthritis. A cross sectional MRI study.

OBJECTIVE: To investigate possible association between sacroiliitis and HLA-B*35 positivity. METHOD: After excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3 months to 2 years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints. RESULTS: A statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25; p = 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3-27, p = 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1-11.9, p = 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75-14.3, p = 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16). CONCLUSION: The data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients. Key Points • HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients. • HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients. • HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.

[Sex hormones, immune disorders, and inflammatory rheumatic diseases]. / Spolni hormoni, imunoloski poremecaji i upalne reumatske bolesti.

It is a well-documented fact that sex hormones are implicated in the immune response and that androgens and estrogens modulate susceptibility and progression of autoimmune rheumatic diseases. Estrogens are considered to stimulate cell proliferation and humoral immune responses while androgens exert suppressive effects on both humoral and cellular immune responses. Autoimmune diseases are common in females, especially during the generative period, the most representative of estrogen-related autoimmune diseases being systemic lupus erythematosus. Estrogens and androgens are involved in the pathogenesis of the disease; both exogenous and endogenous estrogens are strong stimulators of cytokine production and disease activity. Some physiological conditions, as well as some drugs and chronic stress, can modulate hormone levels. Low levels of gonadal androgens have been detected in body fluids of both male and female rheumatoid arthritis patients, supporting the possibility of the pathogenic role for decreased androgen levels. Views on hormone replacement therapy or hormonal contraception in rheumatic diseases have been modified and in most rheumatic diseases, including rheumatoid arthritis, hormones are not prohibited. There are still controversies regarding systemic lupus; the new standpoint being that hormonal contraception is not contraindicated in women with inactive or stable active SLE, except for those with positive antiphospholipid antibodies.

[Clinical approach to a patient with rheumatoid arthritis]. / Klinicki pristup bolesniku s reumatoidnim artritisom.

Rheumatoid arthritis (RA) is chronic inflammatory rheumatic disease which leads to joint damage, functional im- pairment and reduced quality of life. The disease should be recognized early when there is a "window of oppor- tunity" to apply adequate treatment which may prevent structural damage. As clinical presentation of RA is not always typical, great knowledge and clinical experience, including collaboration of rheumatologist, general practi- tioner and patient, are required. The treatment should be started immediately upon the diagnosis, while the choice of modality of treatment depends on the rheumatologist in accordance with the patient. The RA patients with the higher risk of aggressive disease need to be recognized because they require more aggressive treatment from the start. The goal of the treatment is remission or at least low disease activity. Current treatment of RA includes disease modifying antirheumatic drugs (DMARDs) synthetics and biologics, nonsteroidal antirheumatic drugs (NSAIDs), glucocorticoids, analgesics, and rarely cytostatics. The course of disease is usually fluctuating with the exchange of relapses and remissions. Recognition of the relapsing patient on time enables treatment intensification or modifications in treatment scheme. Special issue in RA represents glucocorticoid-induced osteoporosis (GIO) which should be prevented by usage of calcium and vitamin D supplements and treated by antiresorptive or osteoanabolic agents. Besides the treatment of the primary disease, the care of RA patients should consider comorbidities, side effects of treatment, complications of disease, and psychosocial aspects of chronic disease.

[The existence of geographical clusters of rheumatiod arhritis according to their origin in a tertiary care based register]. / Postojanje zemljopisnih klastera reumatoidnog artritisa na osnovu podrijetla prema podacima tercijarnog centra.

The objective was to analyse epidemiological tendencies of rheumatoid arthritis (RA) in Dalmatia County in order to identify possible spatial clusters of RA. Patient-interviewers were trained to administer telephone surveys. 197 RA patients controlled at Rheumatology and immunology department of Clinical hospital of Split were mapped to place of residence by telephone survey. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. Four clusters were identified; the largest one was in the region of Sinj. The female/male ratio was 5.79:1. Majority of RA patients were among age 50 to 59 (30.45 %). The results show inter-regional variations with the marked clusters in the north of Dalmatia suggesting that clusters with higher incidence of RA have specific genetic and environmental background. Prevalence of RA in female was higher than in current literature, while the age of onset 50-59 years is similar with data from recent studies.

[Paraneoplastic hypertrophic osteoarthropathy]. / Paraneoplasticna hipertroficna osteoartropatija.

Hypertrophic osteoarthropathy is a syndrome presenting with dclubbing, limbs enlargement, pain and swelling of foot and long bones osteitis. Hypertrophic osteoarthropathy is a rare paraneoplastic syndrome in the patients with primary or metastatic lung cancer. We report 39-year old female patient who presented with arthritis and paraneoplastic hypertrophic osteoarthropathy revealing lung adenocarcinoma.

[Vaccination in chronic autoimmune and inflammatory rheumatic diseases]. / Cijepuenje u kronicnim autoimunim i upalnim reumatskim bolestima.

Vaccine preventable infections occur more often in patients with autoimmune and chronic rheumatic diseases when compared to the general population. Most vaccines are immunogenic, efficacious and safe in those patients, even with immunosuppressive treatment, excluding rituximab. Live attenuated vaccines should be avoided in patients receiving long-term immunosuppressive therapy. The occurrence of adverse events and autoimmune phenomena is almost the same in vaccinated patients with rheumatic diseases and in vaccinated healthy individuals. A deeper research is needed regarding safety of vaccination and the influence of new immunomodulating drugs on efficacy of vaccination since the studies that were undertaken so far are retrospective or performed on small cohorts of patients. Evidence-based recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases developed by European League Against Rheumatism (EULAR) will help rheumatologists in making a decision about vaccinating their patients.

[Treatment of systemic lupus erythematosus]. / Lijeccenje sistemskog eritemskog lupusa.

Treatinent of systemic lupus erythematosus is very difficult because of heterogeneous clinical manifestations. Standard therapy includes non-steroidal anti-inflammatory drugs, glucocorticoids, anitimalarials and cytotoxic agents. A numerous biological agents have been investigated for treatment of the systemic lupus erythematosus. They are directed to B and T cell depletion, blockade of co-stimulatory molecules, inhibition of cytokines and complement modulation. Sirolimus, tacrolimus, autologous hematopoietic stem cell transplantation and allogenic mesenchymal stem cells transplantation have been also investigated for treatment of systemic lupus erythematosus.

[Polymyositis, dematomyositis: overlap syndromes with connective tissue diseases and malignancies]. / Polimiozitis, dermatomiozitis: sindromi preklapanja s autoimunim i malignim bolestima.

Polymyositis and Dermatomyositis are often connected with autoimmune diseases and are closely linked with specific autoantibodies. Clinical manifestations are mild in correlation with clinical picture ofmyositis related to malignancy. Pulmonary complications are main cause of mortality in overlap syndromes with autoimmune diseases. Infection, cardiovascular complications and underlying malignancy provide greater mortality risk.