[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.

[Psoriatic arthritis : Overview of drug therapy options and administration characteristics]. / Psoriasisarthritis : Übersicht medikamentöser Therapieoptionen und Anwendungsbesonderheiten.

Psoriatic arthritis is a chronic inflammatory disease of the musculoskeletal system with association to skin psoriasis and is characterized by variable clinical symptoms with very heterogeneous degrees of disease suffering for patients. Clinical manifestations essentially include alterations to the skin and nails, peripheral arthritis, enthesitis, dactylitis and/or spinal involvement. This variability necessitates an individualized therapy of patients with different therapy targets. Apart from international guidelines no therapy recommendations are available in Germany for treatment of psoriatic arthritis. For this reason this article summarizes the established points, characteristics and aspects to be considered in the therapy of psoriatic arthritis in Germany, taking the various main forms of the disease into consideration.

[Psoriatic arthritis : Overview of drug therapy options and administration characteristics]. / Psoriasisarthritis : Übersicht medikamentöser Therapieoptionen und Anwendungsbesonderheiten.

Psoriatic arthritis is a chronic inflammatory disease of the musculoskeletal system with association to skin psoriasis and is characterized by variable clinical symptoms with very heterogeneous degrees of disease suffering for patients. Clinical manifestations essentially include alterations to the skin and nails, peripheral arthritis, enthesitis, dactylitis and/or spinal involvement. This variability necessitates an individualized therapy of patients with different therapy targets. Apart from international guidelines no therapy recommendations are available in Germany for treatment of psoriatic arthritis. For this reason this article summarizes the established points, characteristics and aspects to be considered in the therapy of psoriatic arthritis in Germany, taking the various main forms of the disease into consideration.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

Effect of certolizumab pegol over 96†weeks in patients with psoriatic arthritis with and without prior antitumour necrosis factor exposure.

OBJECTIVE: Previous reports of RAPID-PsA (NCT01087788) demonstrated efficacy and safety of certolizumab pegol (CZP) over 24 weeks in patients with psoriatic arthritis (PsA), including patients with prior antitumour necrosis factor (TNF) therapy. We report efficacy and safety data from a 96-week data cut of RAPID-PsA. METHODS: RAPID-PsA was placebo-controlled to week 24, dose-blind to week 48 and open-label to week 216. We present efficacy data including American College of Rheumatology (ACR)/Psoriasis Area and Severity Index (PASI) responses, HAQ-DI, pain, minimal disease activity (MDA), modified total Sharp score (mTSS) and ACR responses in patients with/without prior anti-TNF exposure, in addition to safety data. RESULTS: Of 409 patients randomised, 273 received CZP from week 0. 54 (19.8%) CZP patients had prior anti-TNF exposure. Of patients randomised to CZP, 91% completed week 24, 87% week 48 and 80% week 96. ACR responses were maintained to week 96: 60% of patients achieved ACR20 at week 24, and 64% at week 96. Improvements were observed with both CZP dose regimens. ACR20 responses were similar in patients with (week 24: 59%; week 96: 63%) and without (week 24: 60%; week 96: 64%) prior anti-TNF exposure. Placebo patients switching to CZP displayed rapid clinical improvements, maintained to week 96. In patients with ≥3% baseline skin involvement (60.8% week 0 CZP patients), PASI responses were maintained to week 96. No progression of structural damage was observed over the 96-week period. In the Safety Set (n=393), adverse events occurred in 345 patients (87.8%) and serious adverse events in 67 (17.0%), including 6 fatal events. CONCLUSIONS: CZP efficacy was maintained to week 96 with both dose regimens and in patients with/without prior anti-TNF exposure. The safety profile was in line with that previously reported from RAPID-PsA, with no new safety signals observed with increased exposure. TRIAL REGISTRATION NUMBER: NCT01087788.

[Septic arthritis in adults]. / Septische Arthritis des Erwachsenen.

Septic arthritis is a true rheumatological emergency requiring immediate and thoughtful effort for rapid diagnosis establishment and treatment initiation. Children and elderly persons as well as immunocompromised individuals, patients with pre-existing joint damage and with inflammatory rheumatic joint diseases are preferentially affected. Bacteremia, joint surgery and intra-articular injections pose risk situations for the development of joint infections. The most frequent causative organism is Staphylococcus aureus but other relevant pathogens include coagulase-negative staphylococci, streptococci and mycobacteria. Synovial fluid analysis (e.g. appearance, cell count and microbiological examination) is the most important step to establish the diagnosis. The two main components of therapy consist of joint drainage and antibiotic treatment. The approach to periprosthetic joint infections depends on the duration of symptoms, causative organism and individual factors.

[Evidence-based recommendations for the management of undifferentiated peripheral inflammatory arthritis (UPIA). The German perspective on the international 3e initiative]. / Evidenzbasierte Empfehlungen zum Management einer undifferenzierten peripheren entzündlichen Arthritis (UPIA). Die deutsche Perspektive zur internationalen 3e-Initiative.

INTRODUCTION: Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations. METHODS: Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice. RESULTS: A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references. CONCLUSIONS: The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.

Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1.

OBJECTIVES: To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. METHODS: Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. RESULTS: A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. CONCLUSIONS: Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blind randomised placebo-controlled study (RAPID-PsA).

OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-PsA (NCT01087788), an ongoing Phase 3 trial in patients with psoriatic arthritis (PsA). METHODS: Patients were randomised 1:1:1 to placebo, 200 mg CZP every 2 weeks (Q2W) or 400 mg CZP every 4 weeks (Q4W). Patients could have had exposure to one previous tumour necrosis factor (TNF) inhibitor therapy. Primary endpoints were American College of Rheumatology 20% (ACR20) response at week 12 and modified Total Sharp Score change from baseline at week 24. Secondary endpoints included; Psoriatic Arthritis Response Criteria (PsARC) score, Health Assessment Questionnaire Disability Index (HAQ-DI), Psoriasis Area and Severity Index, Leeds Enthesitis Index, Leeds Dactylitis Index, and Modified Nail Psoriasis Severity Index. RESULTS: Of 409 patients randomised, 368 completed 24 weeks of treatment. ACR20 response was significantly greater in CZP 200 mg Q2W and 400 mg Q4W-treated patients than placebo (58.0% and 51.9% vs 24.3% (p<0.001)) at week 12, with improvements observed by week 1. There was a statistically significant improvement in physical function from baseline, measured by HAQ-DI in CZP patients compared with placebo (-0.50 vs -0.19, p<0.001) and more patients treated with CZP 200 mg Q2W and CZP 400 mg achieved an improvement in PsARC at week 24 than placebo (78.3% and 77.0% vs 33.1% (p<0.001)). Sustained improvements were observed in psoriatic skin involvement, enthesitis, dactylitis and nail disease. Higher ACR20 response with CZP was independent of prior TNF inhibitor exposure. No new safety signals were observed. CONCLUSIONS: Rapid improvements in the signs and symptoms of PsA, including joints, skin, enthesitis, dactylitis and nail disease were observed across both CZP dosing regimens.

Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomised placebo-controlled study of certolizumab pegol.

OBJECTIVES: To report the effect of different imputation methodologies on the assessment of radiographic progression in clinical trials. METHODS: The 216-week RAPID-psoriatic arthritis (PsA) (NCT01087788) trial of certolizumab pegol (CZP) in patients with active PsA was double-blind and placebo-controlled until week 24. A primary end point was change from baseline in modified Total Sharp Score(s) (mTSS). Prespecified imputation methodology in patients with fewer than two analysable mTSS used minimum observed baseline score for missing baseline values and maximum observed week 24 score for missing week 24 values. Post hoc analyses used alternative methods of imputation in patients with fewer than two analysable mTSS. mTSS non-progressors were defined as patients with ≤0 (predefined) or ≤0.5 (post hoc) change in mTSS from baseline to week 24. Baseline mTSS and C-reactive protein levels as predictors of radiographic progression were investigated. RESULTS: 409 patients were randomised. Baseline demographics were similar between groups. Prespecified imputation analysis inappropriately overestimated radiographic progression (least squares mean placebo, 28.9; CZP, 18.3; p≥0.05). Multiple post hoc analyses demonstrated that CZP inhibited radiographic progression compared with placebo, particularly in patients with high baseline mTSS and C-reactive protein levels. mTSS non-progression rate was higher in CZP than placebo groups in all analyses. CONCLUSIONS: Inappropriate prespecified imputation methodology resulted in an unrealistic assessment of progression in all arms. Methodologies for imputing missing radiographic data can greatly affect assessment and reporting of mTSS progression.

Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2.

OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.

[Infection-induced reactive arthritis : etiopathogenesis, clinical spectrum, therapy]. / Infektinduzierte reaktive Arthritiden : Ätiopathogenese - klinische Manifestationen - Therapie.

Reactive arthritis is an inflammatory joint disease induced by a preceding, sometimes asymptomatic bacterial infection outside the joints. With an estimated prevalence of 40/100,000 inhabitants, the disease primarily affects adults between the ages of 20 and 40 years. The clinical presentation is typically characterized by monoarthritis to oligoarthritis of the lower extremities with possible accompanying enthesitis, bursitis, tenosynovitis, sacroiliitis, dactylitis and rare extra-articular manifestations. Because of the similar clinical symptoms and an association with HLA-B27, reactive arthritis is attributed to the spondyloarthropathies. Typical triggering pathogens are Chlamydia, Salmonella, Yersinia, Shigella and Campylobacter. In about 20% of the cases the usually self-limiting disease becomes chronic. The pathogenesis is not yet understood in detail but it is currently assumed that the intracellular persistence of the pathogen causes an immune reaction resulting in arthritis. Common international diagnostic criteria do not yet exist; therefore the diagnosis is made largely on the basis of clinical findings, medical history and the direct and/or indirect pathogen detection. Several therapeutic options are used to treat reactive arthritis. Ongoing extra-articular infections, with the exception of enteritis should be treated with antibiotics. Besides symptom-orientated treatment of acute arthritis, in prolonged and chronic reactive arthritis an immunomodulatory therapy with steroids, sulfasalazine or methotrexate is used. The role of long-term antibiotic therapy for eradication of persistent intra-articular pathogens in chronic cases is the subject of current research.

The new 2012 German recommendations for treating rheumatoid arthritis : differences compared to the European standpoint.

The German Society for Rheumatology recently published guidelines for the sequential therapy of rheumatoid arthritis (RA). These recommendations were developed as a transition from the 2010 EULAR (EUropean League Against Rheumatism) recommendations to the national clinical practice and are based on an updated systematic literature research and expert discussion. While most EULAR recommendations have remained unchanged, some were modified based on new evidence from randomized, controlled trials, current clinical practice, or national drug approval status. The guidelines also include a treatment algorithm for sequential therapy of RA with disease-modifying agents including biologics.

[Inflammatory rheumatic diseases in the elderly: rheumatoid arthritis and polymyalgia rheumatica]. / Entzündlich-rheumatische Erkrankungen im höheren Lebensalter: Rheumatoide Arthritis und Polymyalgia rheumatica.

Inflammatory rheumatic diseases with first onset in advanced age have some specific clinical features. Late-onset rheumatoid arthritis and polymyalgia rheumatica/giant cell arteriitis are the most relevant rheumatic diseases among older patients. They are characterized by acute onset, early functional impairment, and difficult differential diagnosis. First-line therapy usually consists of glucocorticoids. During long-term therapy, a spectrum of immunosuppressive agents and biologicals can also be used in elderly patients.

[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.

[Systematic literature research for S1 guidelines on sequential medical treatment of rheumatoid arthritis]. / Systematische Literaturrecherche für die S1-Leitlinie zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis.

BACKGROUND: On behalf of the German association of Rheumatology national experts developed guidelines for the medical treatment of rheumatoid arthritis (RA) based on the EULAR recommendations for the management of RA published in 2010. Current evidence was provided with an update of the systematic literature review (SLR). The methods and results of the SLR are presented in this article. MATERIALS AND METHODS: An update of the EULAR SLR for the medical treatment of RA was performed from January 2009 to August 2011. The SLR assessed all controlled studies dealing with the outcome in clinical aspects, function and structure of disease modifying treatment of RA. RESULTS: Out of 6,869 screened publications, 138 articles and 56 abstracts were considered in the development of the German guidelines on the treatment of RA. A modified set of recommendations was approved in a consensus of national experts. CONCLUSION: A systematic literature research provided current evidence for the German recommendations on the sequential medical treatment of RA.

[Bacterial septic arthritis as rheumatological emergency]. / Bakteriell septische Arthritis als rheumatologischer Notfall.

Septic arthritis has always been a challenge to rheumatologists and surgeons. Treatment according to the current classification needs to be stage-adapted and has to be initiated rapidly as the time factor constitutes the key prognostic criterion. Failure to treat and late treatment initiation result in irreversible joint damage, functional impairment and increasing mortality. Particularly in cases of acute joint infection, clinical findings, laboratory markers of inflammation and synovial analysis lead to a rapid diagnosis of empyema in most cases. However, chronic septic arthritis may be associated with considerable diagnostic problems. In these cases further diagnostic methods, e.g. magnetic resonance imaging (MRI), computed tomography (CT) and skeletal scintigraphy may be needed. Consideration of prior treatment, extent of the infection and of the degree of joint damage is of high clinical relevance. After an optional initial antibiotic pretreatment, definitive surgical treatment is always necessary either arthroscopically or using open techniques, depending on the stage of infection. Both surgical techniques have comparable treatment success rates. Surgical radicality in removing the infected tissue is of high importance. Local and systemic antibiotic treatment is of adjuvant and supportive value. An intensive physical therapy should be initiated early to avoid functional deficits.