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.

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-month lockdown in Germany. METHODS: From 16th March until 15th June 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 that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the 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 behaviour 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 recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

[A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic]. / Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie ­ eine Situationsanalyse.

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

Different risk profiles of biologic agents for new-onset psoriasis in patients with rheumatoid arthritis.

OBJECTIVE: To investigate rates and risk factors for incident and recurrent psoriasis in rheumatoid arthritis (RA) patients treated with different biologic (b) and conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). METHODS: RA patients enrolled in the German biologics register RABBIT without (n = 14,525) or with a history of psoriasis (n = 375) were analyzed separately. All first events of psoriasis reported until October 2017 were assigned to the treatments prescribed in the previous 3 months. Crude incidence rates (IR) of psoriasis were calculated per 1000 patient-years. To investigate risk factors for psoriasis, cox regressions with and without inverse probability weights were applied to adjust for confounding by indication. RESULTS: 117 incident and 37 recurrent psoriatic events were reported. Patients exposed to TNFi had a significantly higher incidence rate (IR = 3.04/1,000 PY) than those exposed to csDMARDs only (IR = 0.65), whereas IRs for abatacept, rituximab and tocilizumab did not differ significantly from csDMARDs. Adjusted Cox regression confirmed a higher risk for TNFi. Female sex (HR: 1.7) and smoking (HR: 2.1) were significantly associated with incident psoriasis while methotrexate decreased the risk (HR: 0.5). For recurrent psoriasis, IRs for TNFi, abatacept and rituximab were significantly higher than for csDMARDs. CONCLUSIONS: Our data confirm a previously observed increased risk of incident psoriasis in patients exposed to TNFi compared to csDMARDs. However, the overall risk is low and the event is usually non-serious. Comedication of TNFi with methotrexate seems to lower the risk of incident psoriasis. In patients with a history of psoriasis, recurrence as adverse event is rare.

[Which patients with rheumatoid arthritis do not receive DMARD treatment? Analysis of data from the German Collaborative Arthritis Centers]. / Welche Patienten mit rheumatoider Arthritis erhalten keine DMARD-Therapie? Eine Analyse von Daten der Kerndokumentation.

BACKGROUND: The vast majority of patients with rheumatoid arthritis (RA) included in the national database of the German Collaborative Arthritis Centers are treated with disease-modifying antirheumatic drugs (DMARD). The clinical and patient-related characteristics of patients who did not have DMARD treatment in the longer term were investigated. METHODOLOGY: Between 2012 and 2016 a total of 10,289 patients with RA were documented. Patient characteristics, disease activity and severity, comorbidities and concomitant treatment were descriptively evaluated. Patients who were without DMARDs for more than 1 year and not in remission (disease activity score 28, simple disease activity index or Boolean remission) were analyzed separately. Logistic regression was used to investigate which variables were associated with DMARD treatment. RESULTS: A total of 426 patients were ≤1 year without DMARDs, 1090 > 1 year without DMARDs and 8773 (85%) currently had DMARD treatment. Of the patients who were without DMARDs for more than 1 year, 51% were in remission. Even if no remission criteria were met, the rheumatologists nevertheless found the strived for RA situation in the majority of patients. Of the patients who were without DMARDs for more than 1 year, 13% received glucocorticoid treatment >5 mg/day. In patients with a high degree of severity (odds ratio, OR severe vs. asymptomatic/mild 2.33, 95% confidence interval, CI 1.80;3.02) or positive rheumatoid factor (OR 2.24, CI 1.96;2.56) the chance of receiving DMARD treatment was twice as high. Existing comorbidities did not reduce the chance of receiving DMARD treatment. CONCLUSION: The RA patients in the national database who had no DMARDs for more than 1 year were mostly in remission or with low disease activity. Signs of inadequate disease control were found in only 11% of all patients without DMARD treatment.

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. / S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten.

BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

[Standards of care for people with rheumatoid arthritis in Europe : Translation and comments of the eumusc.net recommendations supported by EULAR performed by a national task force of the professional organisations DGRh and VRA supported by "Deutsche Rheumaliga"]. / Europäische Versorgungsstandards für Menschen mit rheumatoider Arthritis : Übersetzung und Kommentierung der von der EULAR unterstützten Vorschläge des eumusc.net durch eine Task Force von DGRh und VRA mit Unterstützung der Deutschen Rheuma-Liga.

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European "standards of care" for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information - this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.

[Do we still need clinical studies in rheumatology?]. / Brauchen wir noch klinische Studien in der Rheumatologie?

Despite a large number of approved therapies demonstrating efficacy in the treatment of rheumatic diseases, only 60-85 % of patients with the indications for rheumatoid arthritis are adequately treated in Germany. Additionally, approved therapies for other immune-mediated diseases are often entirely lacking, indicating the great medical need for the development of new innovative therapies in this specialized field. The development of new drugs is expensive due to the high costs of conducting clinical trials in all phases of development up to obtaining approval; therefore, pharmaceutical companies are looking for ways to save costs in the particular developmental stages. Although the classical regions for drug development (i.e. western Europe, the USA and Japan) offer both a high level of data quality and a good infrastructure to conduct clinical trials due to high standards of education and quality, clinical trials are expensive in these regions. Beside high costs, the comparatively low recruitment rates in these regions are one of the main reasons for the shifting of drug developmental stages from classical regions to eastern European, Latin American and Asian countries, which provide services for drug development and high recruitment rates for comparatively less money. However, there are many strong arguments for the participation of regions in western Europe, especially German sites in clinical trials. In this article these arguments are discussed and possible solutions and strategies for conducting and compensation of study centers in Germany for clinical trials in the field of rheumatology are provided.

Clinical outcomes and safety of rituximab treatment for patients with systemic lupus erythematosus (SLE) - results from a nationwide cohort in Germany (GRAID).

OBJECTIVE: The objective of this article is to evaluate the safety and clinical outcome of rituximab treatment in systemic lupus erythematosus (SLE) patients refractory to standard of care therapy in a real-life setting in Germany. METHODS: The GRAID registry included patients with different autoimmune diseases who were given off-label treatment with rituximab. Data on safety and clinical response were collected retrospectively. In SLE patients, clinical parameters included tender and swollen joint counts, fatigue, myalgia, general wellbeing, Raynaud's and the SLEDAI index. Laboratory tests included dsDNA antibody titres, complement factors, hematologic parameters and proteinuria. Finally, the investigators rated their patients as non-, partial or complete responders based on clinical grounds. RESULTS: Data from 85 SLE patients were collected, 69 female and 16 male, with a mean disease duration of 9.8 years. The mean follow-up period was 9.6 ± 7.4 months, resulting in 66.8 patient years of observation. A complete response was reported in 37 patients (46.8%), partial response in 27 (34.2%), no response in 15 (19.0%). On average, major clinical as well as laboratory efficacy parameters improved substantially, with the SLEDAI decreasing significantly from 12.2 to 3.3 points. Concerning safety, one infusion reaction leading to discontinuation of treatment occurred. Infections were reported with a rate of 19.5 (including six severe infections) per 100 patient years. CONCLUSION: With the restrictions of a retrospective data collection, the results of this study confirm data of other registries, which suggest a favourable benefit-risk ratio of rituximab in patients with treatment-refractory SLE.

[German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm]. / S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012. Adaptierte EULAR-Empfehlungen und aktualisierter Therapiealgorithmus.

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

A dose of only 5 mg prednisolone daily retards radiographic progression in early rheumatoid arthritis - the Low-Dose Prednisolone Trial.

Glucocorticoids (GC) have been used to treat rheumatoid arthritis (RA) for more than 60 years. Despite this very long experience, there remains considerable debate concerning the adequate dosing and timing of these medications, primarily because of frequent and sometimes serious side effects, particularly in high doses. GCs are documented to provide immediate symptomatic relief and to decrease signs of inflammation in active disease. At the time when the Low-Dose Prednisolone Trial (LDPT) was designed, no clear evidence was available concerning whether low doses of GCs given over a long period add to slowing of structural damage in RA. The trial was therefore designed to test the hypothesis that even a low dose of prednisolone that was thought to cause no or only very limited harm could slow radiographic progression. The trial therefore included patients with active early RA (disease duration less than two years) who received either prednisolone 5 mg/day or placebo on concomitant DMARD therapy with parenteral gold or methotrexate for two years. Radiographs of hands and feet were taken at baseline, and at 6, 12 and 24 months. Structural damage was assessed using change in the Ratingen score (0-190 scale) as the primary outcome, and change in the Sharp/van der Heijde score (0-448 scale) for additional information concerning the same radiographs. Of 192 patients in the study, 166 were available for intention to treat analysis (ITT), and 76 completed the study per protocol (PP). Progression of the Ratingen score was significantly less at all consecutive time points in the prednisolone group compared to the control group, with the greatest difference after 6 months. At 24 months the increase in score in the prednisolone group was 1.2 ± 3.5, (95% CI 0.4-2.1) and in the placebo group 4.3 ± 6.8 (95% CI 2.7-5.9) (p=0.006, ITT-analysis). This was confirmed by the results of the Sharp/van der Heijde erosion and total score with an increase of the total score of 5.3 ± 10.7 units in the prednisolone compared to 11.4 ± 19.1 in the placebo group (p=0.022) at 24 months. The LDPT trial therefore confirmed that a very low daily dose of 5 mg prednisolone given over two years in combination with background DMARD therapy substantially decreases radiographically detectable damage in patients with early RA.

[Patient/rheumatologist evaluation of infusion treatment for rheumatoid arthritis]. / Bewertung einer Infusionbehandlung der rheumatoiden Arthritis durch Patienten und Rheumatologen.

OBJECTIVES: The various biologic agents currently available for the treatment of RA can be administered subcutaneously (s.c.) or via intravenous (i.v.) infusion with variable intervals depending on the drug. This investigation aims to identify the preferences and concerns of affected patients and their physicians. METHODS: We conducted a survey of 102 patients with RA currently receiving Rituximab (RTX) therapy. They were asked about different aspects of their current and previous RA therapy, including overall satisfaction, tolerability, mode of drug administration, as well as duration and intervals. In addition, 17 rheumatologists were asked about different aspects of s.c. or i.v. drug administration, their preference and the suspected preference of their patients. RESULTS: The mean age of our patients was 59 ± 11.2 years. Patients had failed ≥2 DMARD therapies and ≥ 1 biologic treatment. The impact of RTX infusions on planning different activities including job, hobbies or travelling was considered as low or very low in 76% of the respondents. Interestingly, 63.4% of patients would prefer an infusion every 6-9 months as RA therapy, whereas 21.5% would prefer tablets only; 12.9% of our patient cohort would prefer s.c. injections every second week, and only 2% would prefer an infusion every month. In all, 92% of patients questioned would choose RTX therapy again. In contrast, 88% of rheumatologists preferred s.c. injection and even 94% of them assumed that their patients would do so as well if they had the choice. The suggested reasons included greater flexibility, convenience and independence during s.c. therapy. CONCLUSION: Contrary to the assumption of rheumatologists, we have demonstrated a preference among RTX patients for i.v. drug administration every 6-9 months over other methods of administration.

[Outcome parameters for use in psoriatic arthritis]. / Outcome-Parameter bei Psoriasisarthritis.

The most important and most commonly occurring form of psoriasis is psoriasis vulgaris. In the specialism of rheumatology palmoplantar pustulosis is also important. The outcome is influenced mainly by how severe and how widespread the manifestations affecting the skin and nails are. All manifestations affecting the joints and occurring in association with psoriasis are subsumed under the term 'psoriatic arthritis' (PsA). Asymmetric oligoarthritis, enthesitis and inflammatory spinal manifestations are especially frequent. PsA is a rheumatic illness with widely varying clinical pictures, most patients having signs and symptoms resembling those of spondyloarthritides (SpA) and other features of rheumatoid arthritis (RA) and/or of arthrosis/osteoarthritis (OA). Clinical features that are particularly typical of PsA are ray-wise joint involvement, dactylitis and osteodestructive and osteoproliferative joint destruction. Dactylitis, asymmetric joint involvement and enthesitis also occur in other SpA. It is becoming increasingly important to define outcome parameters for use in PsA against the backdrop of new forms of treatment. In the case of clinical outcome basic distinctions must be made between clinical signs and symptoms, function and structure. In PsA the sometimes significant manifestations affecting skin and nails must also be considered. The outcome parameters used thus far have varied very widely. The extent and intensity of involvement of the peripheral joints and insertions of tendons and of spinal involvement are particularly important in PsA. In addition, functional impairments, quality of life and parameters concerned with work must be considered. There are hardly any measuring instruments specific to PsA; many have been developed and used primarily for SpA or RA.

The Infliximab Multinational Psoriatic Arthritis Controlled Trial (IMPACT): results of radiographic analyses after 1 year.

OBJECTIVE: Infliximab is effective in improving signs and symptoms of joint/skin involvement, functional status, and quality of life in patients with psoriatic arthritis (PsA). Using IMPACT trial data, we assessed the effect of infliximab (IFX) on structural damage in PsA. METHODS: Patients with active PsA were randomly assigned to receive placebo (PBO/IFX) or infliximab 5 mg/kg (IFX/IFX) at weeks 0, 2, 6, and 14, with the primary endpoint at week 16. The PBO group received infliximab loading doses at weeks 16, 18, and 22. Thereafter, all patients received infliximab 5 mg/kg every 8 weeks through week 50. Hand/feet radiographs were obtained at weeks 0 and 50. Total radiographic scores were determined using the PsA modified van der Heijde-Sharp (vdH-S) score. Projected annual rate of progression was calculated by dividing x ray score by disease duration (years). RESULTS: As reported previously, 65% of infliximab treated patients versus 10% of PBO treated patients achieved an ACR20 response at week 16 (p<0.001). At week 50, 69% of patients achieved an ACR20 response. Radiographs (baseline and week 50) were available for 72/104 patients. At baseline, estimated mean annual rate of progression was 5.8 modified vdH-S points/year. Mean (median) changes from baseline to week 50 in the total modified vdH-S score were -1.95 (-0.50) for PBO/IFX and -1.52 (-0.50) for IFX/IFX patients (p = NS). At week 50, 85% and 84% of patients in the PBO/IFX and IFX/IFX groups had no worsening in the total modified vdH-S score. CONCLUSION: Infliximab inhibits radiographic progression in patients with PsA through week 50.

[Imaging techniques in rheumatology: conventional radiography in rheumatoid arthritis]. / Bildgebende Verfahren in der Rheumatologie: Konventionelle Röntgendiagnostik bei der rheumatoiden Arthritis.

Conventional radiography is still regarded the gold standard for imaging techniques in rheumatoid arthritis (RA). It is a very important tool for the diagnosis, the differential diagnosis, and the evaluation of the course and prognosis of the disease. Special advantages of conventional radiography are the worldwide availability and experience with the method over decades and the relatively low costs. Moreover, x-rays can be stored and re-evaluated over long periods of time. Joint damage caused by RA can be quantified by means of scoring methods. The amount of destruction correlates well with functional disability over time. The inhibition of damage progression seen on radiographs is the most important characteristic of a DMARD. Typical radiographic changes are part of the ACR classification criteria of RA. Technically, bone structure can be demonstrated with a high local resolution better than with all other imaging techniques, whereas only indirect conclusions can be drawn concerning soft tissue and cartilage lesions. This review includes recommendations given by the "Commission on Imaging Techniques" of the German Society of Rheumatology regarding technical and personal preconditions, costs, indication as well as practical performance of radiography in RA. In addition, radiographic changes that can be expected in RA including destruction and repair are discussed briefly.

Treatment continuation in patients receiving biological agents or conventional DMARD therapy.

OBJECTIVE: To compare drug continuation rates in patients with rheumatoid arthritis who start on a biological agent and in a control group of patients with a change in disease modifying antirheumatic drug (DMARD) treatment after previous DMARD failure. METHODS: Patients with rheumatoid arthritis enrolled in the German biologics register between May 2001 and September 2003 were included in the study. Data were available for 511 patients treated with etanercept, 343 with infliximab, 70 with anakinra, and 599 controls. Propensity scores were used to select a subsample of patients from the control group who were likely to be treated with biological agents because of their disease severity, as well as comparable infliximab and etanercept cases. RESULTS: Treatment continuation after 12 months was similar for etanercept (68.6% (95% confidence interval, 62% to 75%)) and infliximab (65.4% (58% to 73%)) but lower for anakinra (59% (41% to 77%)). Treatment continuation was more likely for patients on combinations of biological agents and DMARDs than for those on infliximab or etanercept alone. Patients treated with biological agents were more severely ill than those in the control group and had more previous DMARD failures. After adjustment for baseline differences, the continuation rates were higher in patients treated with biological agents than in comparable control patients treated with leflunomide or leflunomide/methotrexate. CONCLUSIONS: Treatment continuation of biological agents in clinical practice is less likely than in randomised clinical trials but more likely than in comparable controls treated with conventional DMARDs.

Psoriatic arthritis imaging: a review of scoring methods.

Structural damage assessed on conventional radiographs is an important outcome measure in psoriatic arthritis. This article reviews the available scoring methods. A full description of the methods is given as well as information on various aspects of validity.

Healing of erosive changes in rheumatoid arthritis.

This is an overview over the history and present state of knowledge of radiographic signs of erosion healing. The existence of healing or repair has been confirmed; different observers agree in the identification of healing; it may be identified without knowing the sequence of the films. As healing indicates that inflammation has discontinued for several months in an individual joint, it might represent a good additional outcome measure in RA clinical trials.

[Imaging techniques in rheumatology: scoring methods in rheumatoid arthritis]. / Bildgebende Verfahren in der Rheumatologie: Scoring-Methoden bei der rheumatoiden Arthritis.

This is a critical overview of existing scoring methods including their basis, their measurement systems, their advantages and disadvantages. Conventional radiography is still-since available everywhere, interpretable and cost effective-the best imaging method to evaluate the course of RA. Scoring methods are designed to semiquantitatively measure radiographically visible changes, especially erosive destruction and-in part-cartilage loss. These methods are well validated, reproducible, and yield similar results in clinical trials. Most methods overestimate early changes and have a clear ceiling effect. Within the time frame of clinical trials radiographic evaluation is not very sensitive to change since the progression of destruction in RA is relatively slow. Moreover, small erosions cannot be detected if they are not at the margin of the bone or if they are superimposed by other bones. Within the Larsen method the definition of grade 1 by soft tissue swelling is disadvantageous: soft tissue swelling is difficult to identify on X-rays, it is a measure of disease activity and not of destruction and is quickly reversible. Joint space narrowing, measured with Sharp's method and its modifications, may be caused by misprojection due to soft tissue swelling with flexion or subluxation of the joint rather than cartilage loss. Since the measurement error of a scoring method is very much dependent on the severity of the disease of the patient population and on the quality of the radiographs, the measurement error and thereby the minimal detectable change (MDC) should be stated for every single clinical trial. Conventional radiographs and scoring methods are still indispensable to measure the influence of treatment on radiographic progression in RA. A future task will be to include in scoring methods the rating of reparative changes which cannot be scored so far.