The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.

Objective. To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA).Methods. MTX-naive patients with active RA (Disease Activity Score in 28 joints >4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n ‫؍‬ 187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n ‫؍‬ 188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks.Results. At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. Conclusion. This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.

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IntroductionWe used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs).MethodsThe analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis).ResultsA prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFα agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFα: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFα agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFα vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFα treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFα agents (P = 1.0).ConclusionsNo significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFα or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.

ObjectiveTo investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ).MethodsIn 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure.Results37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non-steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2−0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-α inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment.ConclusionsThe incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation.

ZusammenfassungDiese DVO Leitlinien, die in erster Linie für Allgemeinmediziner und Spezialisten für Knochenerkrankungen bestimmt sind, sollten von allen im klinischen und ambulanten Bereich tätigen medizinischen Fachkräften angewendet werden. Ziel der Leitlinie ist die Verbesserung der Diagnose, Prävention und Behandlung von Osteoporose und der Folgen der Erkrankung auf der Grundlage evidenzbasierter Medizin.Klare Empfehlungen, welche Patienten zu diagnostizieren und behandeln sind (basierend auf Risikofaktoren [einschließlich sekundärer Osteoporose]) sowie Primär-, Sekundär- oder Tertiärprävention werden dargestellt, mit dem Schwerpunkt auf der postmenopausalen Osteoporose und der Osteoporose bei Männern.Die Identifizierung von Patienten mit einem hohen Risiko für Frakturen wird hervorgehoben, und spezifische Schwellenwerte für die Intervention sind definiert (20 % Hüftfrakturrisiko innerhalb von 10 Jahren diagnostischer Schwellenwert, 30 % Hüftfrakturrisiko innerhalb von 10 Jahren therapeutische Schwelle). Die Diagnose von Osteoporose basiert auf der Anamnese des Patienten, der körperlichen Untersuchung, dem Funktionstest (z. B. Timed Up and Go Test), konventionellen Röntgenaufnahmen der Brust- und Lendenwirbelsäule und der Bestimmung der Knochenmineraldichte (BMD) durch das DXA Verfahren.Die Anamnese ist entscheidend für die Abschätzung des Frakturrisikos auf der Grundlage von 40 wissenschaftlich überprüften Risikofaktoren, die das Frakturrisiko mindestens verdoppeln (z. B. Begleiterkrankungen, Hüftfrakturen in der Familie, prävalente Frakturen an jedem Ort, Lebensstil, Anwendung von Medikamenten, körperliche Aktivität und Stürze). Röntgenaufnahmen der Brust- und Lendenwirbelsäule sind wichtig, um prävalente Wirbelkörperfrakturen zu erkennen. Beim Fehlen eines großen Traumas kann jede Fraktur bei Erwachsenen über dem Alter von 50 Jahren eine Diagnose von Osteoporose nahelegen, mit dem höchsten Risiko für eine nachfolgende Fraktur innerhalb einer kurzen Zeit nach der ersten Fraktur. BMD-Messungen mit DXA sind wichtig, um das individuelle Frakturrisiko besser abschätzen zu können. Eine grundlegende Laboruntersuchung ist obligatorisch, um verschiedene Formen der sekundären Osteoporose ausschließen zu können.Der DVO-Patientenfindungs-Algorithmus basiert auf dem Geschlecht, Alter, Knochenmineraldichte und vorbestehenden Frakturen als wichtigste Informationen. Die Indikation für eine aktive anti-osteoporotische Therapie kann durch multiple Risikofaktoren modifiziert und verfeinert werden. Dieser Algorithmus wurde seit dem Richtlinien-Update 2006 verwendet und wurde entsprechend der internationalen Literatur zu Risikofaktoren für Osteoporose und osteoporotische Frakturen aktualisiert und angepasst.Die Behandlung der Osteoporose enthält viele Therapiepfeiler. Zusammen mit Empfehlungen für Bewegung, Physiotherapie und Sturzprävention sowie Ernährung (z. B. Calcium, Vit. D), werden pharmakologische Behandlungen basierend auf evidenzbasierter Medizin empfohlen. Die aktiven Anti-Osteoporose-Medikamente müssen für die Indikation postmenopausale Osteoporose und männliche Osteoporose in Deutschland, Österreich und der Schweiz zugelassen sein. Das Management und die Vorbeugung von häufigen oder seltenen Nebenwirkungen aufgrund von Anti-Osteoporose-Behandlungen, die in der klinischen Praxis angewendet werden, werden ebenfalls detailliert behandelt.

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of a functional status above defined thresholds ('functional remission', 'physical independence') in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis -Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2-3.2)); ARA remission, OR 2.05 (95% CI 1.2-3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (≤50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (≥67% of full function) than controls (OR 3.88 (95% CI 1.7-8.8)). 'Functional remission' (≥83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04-4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.

Objective. To compare the 24-month course of health-related quality of life (HRQoL) in patients with long-standing RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) DMARD in daily rheumatological care.Methods. Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients’ HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores.Results. All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%.Conclusion. Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population.