key: cord-0944146-5fn92281 authors: Hasseli, R; Müller-Ladner, U; Keil, F; Broll, M; Dormann, A; Fräbel, C; Hermann, W; Heinmüller, C-J; Hoyer, B F; Löffler, F; Özden, F; Pfeiffer, U; Saech, J; Schneidereit, T; Schlesinger, A; Schwarting, A; Specker, C; Stapfer, G; Steinmüller, M; Storck-Müller, K; Strunk, J; Thiele, A; Triantafyllias, K; Vagedes, D; Wassenberg, S; Wilden, E; Zeglam, S; Schmeiser, T title: The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication - a cross sectional study over 3 months in Germany date: 2021-03-11 journal: Rheumatology (Oxford) DOI: 10.1093/rheumatology/keab230 sha: f93b86060a9493c8f62222ef2ee1605208c7162d doc_id: 944146 cord_uid: 5fn92281 OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-months lockdown in Germany. METHODS: From March 16(th) until June 15(th) 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments which included rheumatology primary care centres and university hospitals participated. 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with rheumatoid arthritis, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). The majority of patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behavior with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendation of the German Society of Rheumatology were well received, supporting the well-established physician-patient-relationship in times of a crisis. To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-months lockdown in Germany. From March 16 th until June 15 th 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments which included rheumatology primary care centres and university hospitals participated. 4252 questionnaires were collected and evaluated. The majority of patients (54%) were diagnosed with rheumatoid arthritis, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). The majority of patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behavior with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendation of the German Society of Rheumatology were well received, supporting the well-established physician-patient-relationship in times of a crisis. More than 48 million cases of infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) were reported globally and more than 1.2 million fatal courses from resulting coronavirus disease 2019 (COVID-19) have been registered as of November 5 th , 2020 [1]. Regardless of these high numbers it has not been fully elucidated whether patients with inflammatory rheumatic diseases (IRD) or specific immunomodulatory treatments have a higher risk to develop a severe course of COVID-19, although data suggest that patients with IRD are at higher risk for bacterial, viral and opportunistic infections compared to the general population [2, 3] . At the beginning of the pandemic, no clear recommendations for patients with IRD were available in Germany. On March 16 th , 2020 hospitals were ordered by the respective authorities to reduce and postpone elective procedures substantially and to prioritize the remaining operative and personnel resources to facilitate treating patients with severe COVID-19. It was recommended that patients should reduce their visits to hospitals and private practices, if not essential for disease management. This caused a dramatic reduction of inand outpatient visits. In some cases, patients did not even receive their immunomodulatory treatment, intravenous application of immunomodulatory drugs were prolonged, necessary adaptions of treatment strategies in case of disease relapse were postponed and personal appointments were nearly completely cancelled to reduce the overall risk of a SARS-CoV-2 infection in Germany [4] . In addition, on March 22 th , 2020 the German government restricted personal contacts outside of family circles to not more than two people, resulting in social isolation. One can quite easily imagine how these measures left some patients completely on their own. Already in April, the German Society for Rheumatology (DGRh), similar to other societies, such as EULAR, BSR and ACR published preliminary recommendations for management of patients with IRD in the context of the current pandemic [5] [6] [7] . All of them suggested the maintenance of immunomodulating therapies during the SARS-CoV-2 pandemic to avoid disease relapses. In order to be able to estimate the patients' behavior with respect to their immunomodulatory therapy, a Germany-wide survey was established during the SARS-CoV-2 pandemic, with a distinct focus on the patients' view on their immunomodulatory therapy. This was based upon the hypothesis that influenced by public media, personal restrictions in the lock-down situation and possibly also by recommendations released from the national rheumatological societies patients may have changed their behavior regarding immunomodulatory therapy [8, 9] . Indeed, this hypothesis was challenged by data of pulmonologists, who showed that pneumological appointments at the beginning of 2020 resulted in an increased adherence to therapy in COPD patients by 15%. However, it could not conclusively be clarified whether improved compliance was due to the context of the impending pandemic [10] . From March 16 th until June 15 th , 2020 IRD patients from private practices and rheumatology departments were anonymously asked for adherence to their immunomodulating therapy. Nine private practices and eight rheumatology departments from 6 federal states across Germany participated. A one-page questionnaire was developed which included the range of age, type of IRD and immunomodulatory treatment (suppl. 1). Patients had to choose one out of seven options to answer this question (suppl. 1). The inclusion criteria were: a) age ≥ 18 years, b) presence of an IRD. There were no inclusion/exclusion criteria for the participating general and private practices and departments. Participation was voluntary and without reimbursement. The time period from March 16 th until March 20 th 2020 was defined as "before lockdown" and the time period from March 21 st until June 15 th 2020 was defined as "during and after lockdown". To investigate further potential reasons, why patients could have discontinued their immunomodulatory therapy, we performed an analysis on "Google Trends" which is a free accessible online portal of Google Inc. [11] . Google Trends allows users to interact with Internet search data, which can provide deep insights into behaviours of the population and healthrelated phenomena [11] . Google Trends answers queries and keeps a record of such searches. The data is compiled to display trends automatically. The weekly trends can be accessed from Google Trends, a special open-access domain of Google (https://trends.google.com/trends/) [12] . We therefore systematically searched for following First, the proportion of patients' characteristics (age, type of IRD, IRD therapy) and opinion were calculated to evaluate relevant changes. Second, exact binomial tests were used to assess significant differences between patients' characteristics and the opinion. Python version 3.8.2 in conjunction with several libraries was used for statistical analyses and for the graphs. P values were 2-sided, and statistical significance was set at P≤ 0.05. Most of the participating centres were located in North Rhine-Westphalia (8) 4B ). In the Google Trends analysis, only for the items "corona steroids", "corona humira", "corona rheuma" sufficient results could be detected. Humira® (adalimumab, manufacturer AbbVie) has been the best-selling bDMARD in Germany for years. We correlated the weekly results of Google Trends for the selected queries with the number of patients who reported to discontinue their immunomodulatory therapy. The weekly course of the number of queries were similar to the course of the number of patients who reported to discontinue their medication ( fig. 5 ). To our knowledge, this study is the largest investigation to light up patients' opinions on immunomodulating therapy in IRD during the SARS-CoV-2 pandemic. The study reflects behavior of IRD patients over a period of 3 months in a lockdown setting with very limited or even no access to rheumatologists nationwide in Germany. In view of these circumstances, rheumatologic societies did not recommend discontinuing the immunomodulatory therapy to avoid disease relapse necessitating new or higher dosage of glucocorticoids putting patients on substantial risk for infections. Our study shows that patients followed these recommendations of rheumatologists. In view of the fact, that the management of patients with IRD was highly impacted by the pandemic, this can be interpreted as a hint for a trustful physician-patient relationship. Other studies could also observe a high number of patients who reported to continue their immunomodulatory therapy [13, 14] . In comparison to these results, medication adherence in patients with arterial hypertension in Germany is estimated to be around 66% in a non-pandemic setting [15] . Of note, no relevant difference in discontinuation rate could be observed with respect to age, type of IRD, type of immunomodulatory drug and the time elapsed since start of the pandemic. As the distribution of age in the study population is comparable to IRD patients in general, the results can be probably transferred to the entirety of IRD patients in Germany. The results in the Google Trends analysis, which show a time-dependent interest for the topics "corona & rheuma", "corona & cortisone" and "corona & humira", could reflect an influence on patients' decision to discontinue their immunomodulatory therapy. A possible reason could be the fear to develop a severe course of SARS-CoV-2 infection due to the immunomodulatory drug. However, this study has some limitations: i) In order to rule out that patients were repeatedly asked for their opinion, the examination interval was limited to three months. Due to the anonymous survey, it is not possible to exclude that patients have participated in the survey more than once. However, as the majority of the patients do not have more than one outpatient visit within three months, a repetition of the survey is most likely only the case for a neglegible number of patients. ii) as the questionnaire was completely anonymous, gender was not recorded, and iii) since it would not be clear at the beginning of the survey that disease activity and the dose of GC could have an influence on the course of a COVID-19, these aspects were not included in the questionnaire; iv) the pandemic is peaking in different regions at different times which might have an influence on the opinion. Although general practitioner and private practices and departments from 6 federal states were involved in the recruitment of the patients, data from other federal states are missing, which could have an impact on the results. In most of the represented federal states, the prevalence of SARS-CoV-2-infections were higher compared to the missing federal states [16] ; v) the study population consists of patients with diseases that are associated with higher risk of severe organ involvement, e.g. vasculitides and connective tissue disease. The prevalence of these diseases in the study population is higher compared to the prevalence among IRD patients in general (suppl. .1 ). The minority of the patients were 18-30 years (6%) old or more than 81 years (4%) old. In 3% of the cases no age was reported. Figure 1B : Distribution of the reported inflammatory rheumatic diseases (in %): 54% of the reported patients suffered from RA; 14% from PsA; 10% from AS; 6% from SLE, 3% from SSc, more than 1% from PM/DM & GPA, 2% from Sjö, 5% from PMR/GCA and 7% from other IRD. Patients had the opportunity to choose between seven answers to describe their adherence to their immunomodulatory medication. Some of the patients chose more than on answer (before: 8%, during and after lockdown 5%). Figure 2A : Patients' behaviour before the national lockdown in Germany: Patients had the opportunity to choose between seven answers to describe their adherence to their immunomodulatory medication. Some of the patients chose more than on answer. Before the national lockdown 57% of the patients reported to continue their immunomodulatory treatment without concern, 15% to continue due to an increased risk of a disease flare, 24% due to lack of alternatives and 5% continued their immunomodulatory drug with concern. Only 3% of the patients reported to discontinue their medication by their own and around 1% in consultation with their rheumatologists. Less than 1% of the patients reported to have no opinion of their treatment and 2% did not choose any option. Figure 2B : Patients' behaviour during and after the national lockdown in Germany: During and after the national lockdown 56% of the patients reported to continue their immunomodulatory treatment without concern, 12% to continue due to an increased risk of a disease flare, 18% due to lack of alternatives and 5% continued their immunomodulatory drug with concern. Around 1% of the patients reported to discontinue their medication by their own and around 1% in consultation with their rheumatologists. 6% of the patients reported to have no opinion of their treatment and less than 1% did not choose any option. Figure 3 : Distribution of discontinue of medication in age: Younger patients (18-30 years old, 2.8%) and patients between 71-80 years old (2.2%) reported less often to discontinue their medication compared to patients between 31-50 years old (4,4%) which were the biggest group followed by 3.7% of the patients between 51-60 years and around 3.6% more than 81 years old and 3,3% of the patients between 61-70 years old SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients Infections and autoimmunity: the multifaceted relationship Auswirkungen von COVID-19 auf die rheumatologische Versorgung : Eine nationale Umfrage im Preliminary recommendations of the German Society of Rheumatology (DGRh eV) for the management of patients with inflammatory rheumatic diseases during the SARS-CoV-2/Covid-19 pandemic EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2 American College of Rheumatology Guidance for the Management of Adult Patients with Rheumatic Disease During the COVID-19 Pandemic Impact of COVID-19 outbreak on rheumatic patients' perceptions and behaviors: A crosssectional study Health-Related Quality of Life in Common Variable Immunodeficiency Italian Patients Switched to Remote Assistance During the COVID-19 Pandemic Changes in medication adherence among patients with asthma and COPD during the COVID-19 pandemic The use of google trends in health care research: a systematic review Google Search Trends Predicting Disease Outbreaks: An Analysis from India The Impact of the COVID-19 Pandemic on Patients with Chronic Rheumatic Diseases: A Study in 15 Covid-19 and Rheumatic and Musculoskeletal Disease Patients: Infection Rates, Attitudes andMedication Adherence Medication Adherence In Patients With Arterial Hypertension: The Relationship With Healthcare Systems' Organizational Factors The authors would like to thank all patients who participated at the survey. RH, TS and UML contributed equally and performed the study design. RH and TS performed the research and the interpretation of the data. FK analysed and performed the statistical analysis. RH wrote the manuscript. All authors performed physician recruitment, contributed to preparation of the project, and read and approved the final manuscript. Biomedical Research (JLU-CAREER) to work on this project. The authors declare that there is no conflict of interest regarding the publication of this article. All datasets generated for this study are included in the article/supplementary material.