Hans Bastian

Validation of a Prediction Rule for Disease Outcome in Patients With Recent-Onset Undifferentiated Arthritis : Moving Toward Individualized Treatment Decision-Making

OBJECTIVE The decision to start disease-modifying antirheumatic drugs in patients with recent-onset undifferentiated arthritis (UA) is complicated by a varied natural disease course in which the disease in one-third of patients progresses to rheumatoid arthritis (RA), whereas 40-50% of patients experience spontaneous remission. Recently, a prediction rule was developed to estimate the chance of progression to RA in individual patients presenting with UA. This study investigates the accuracy of this prediction rule in independent cohorts of patients with UA. METHODS In 3 cohorts of patients with recent-onset UA, from the UK, Germany, and The Netherlands, the prediction score and the corresponding chance of developing RA were calculated. These data were compared with the observed disease outcome after > or =1 year of followup. Positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and the overall discriminative ability of the prediction rule was assessed using area under the receiver operating characteristic curves (AUCs). RESULTS Since data on the severity of morning stiffness were not available in all validation cohorts, the prediction rule was rederived with the duration of morning stiffness as a substitute. The AUC for this rule was 0.88 (SEM 0.015). For each validation cohort, the AUC was 0.83 (SEM 0.041), 0.82 (SEM 0.037), and 0.95 (SEM 0.031) in the British, German, and Dutch cohorts, respectively. The NPV (for a prediction score < or =6) in these 3 cohorts was 83%, 83%, and 86%, respectively; the PPV (for a prediction score > or =8) was 100%, 93%, and 100%, respectively. CONCLUSION The recently derived prediction rule, when applied to 3 independent cohorts of patients with UA, has an excellent discriminative ability for assessing the likelihood of progression to RA. Application of this rule will allow individualized treatment decision-making for patients with UA.

Induction therapy with adalimumab plus methotrexate for 24 weeks followed by methotrexate monotherapy up to week 48 versus methotrexate therapy alone for DMARD-naïve patients with early rheumatoid arthritis: HIT HARD, an investigator-initiated study

Objective To investigate the long-term effects of induction therapy with adalimumab (ADA) plus methotrexate (MTX) in comparison with placebo (PBO) plus MTX in DMARD-naïve patients with active early rheumatoid arthritis (RA). Methods Patients with active early RA (disease duration of ≤12 months) were randomly assigned to receive 40 mg ADA subcutaneously every other week (eow) plus MTX 15 mg/week subcutaneously or PBO plus MTX subcutaneously at 15 mg/week over 24 weeks. Thereafter, all patients received MTX monotherapy up to week 48. The primary outcome was the Disease Activity Score 28 (DAS28) at week 48. Secondary outcomes included proportions of patients in remission (DAS28<2.6), ACR responses, Health Assessment Questionnaire (HAQ) score and radiographic progression. Results 87 patients were assigned to ADA/MTX and 85 patients to PBO/MTX. At baseline, DAS28 was 6.2±0.8 in the ADA/MTX and 6.3±0.9 in the PBO/MTX groups. At week 24, treatment with ADA/MTX compared with PBO/MTX resulted in a greater reduction in DAS28 (3.0±1.2 vs 3.6±1.4; p=0.009) and other secondary outcomes such as DAS28 remission rate (47.9% vs 29.5%; p=0.021) and HAQ (0.49±0.6 vs 0.72±0.6; p=0.0014). At week 48, the difference in clinical outcomes between groups was not statistically significant (DAS28: 3.2±1.4 vs 3.4±1.6; p=0.41). Radiographic progression at week 48 was significantly greater in patients administered PBO/MTX (Sharp/van der Heijde score: ADA/MTX 2.6 vs PBO/MTX 6.4; p=0.03, Ratingen score: 1.7 vs 4.2; p=0.01). Conclusions A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).

Delays in assessment of patients with rheumatoid arthritis: variations across Europe

Objective The first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment of patients with RA in eight European countries. Method Data on the following levels of delay were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw and Zurich): (1) from onset of RA symptoms to request to see healthcare professional (HCP); (2) from request to see HCP to assessment by that HCP; (3) from initial assessment by HCP to referral to rheumatologist; and (4) from referral to rheumatologist to assessment by that rheumatologist. Results Data were collected from 482 patients with RA. The median delay across the 10 centres from symptom onset to assessment by the rheumatologist was 24 weeks, with the percentage of patients seen within 12 weeks of symptom onset ranging from 8% to 42%. There were important differences in the levels underlying the total delays at individual centres. Conclusions This research highlights the contribution of patients, professionals and health systems to treatment delay for patients with RA in Europe. Although some centres have strengths in minimising certain types of delay, interventions are required in all centres to ensure timely treatment for patients.

Effects of early rituximab retreatment in rheumatoid arthritis patients with an inadequate response after the first cycle: retrospective arthritis cohort study.

To the Editor: The therapeutic options for rheumatoid arthritis (RA) have been significantly improved by the introduction of novel biological agents1. In this context the chimeric anti-CD20 monoclonal antibody rituximab (RTX) was approved for treatment of active and resistant RA in Germany in 2006. RTX was shown to represent a safe and effective treatment option over several courses leading to selective and transient depletion of the CD20+ B cell population2–4. However, to date the optimal timepoint for retreatment has not been defined exactly, and longterm treatment strategies using RTX have not been established. Our observational cohort study was performed to compare different treatment strategies using RTX and especially the effects of early retreatment within 4 to 6 months after first drug administration with a retreatment interval of more than 6 months in patients with RA (Figure 1). Baseline characteristics of the 39 RA patients are shown in Table 1. The respective comorbidities included overlapping chronic … Address correspondence to H. Bastian, Department of Rheumatology and Clinical Immunology, Charite – Universitatsmedizin Berlin, Campus Mitte, Chariteplatz 1, 10117 Berlin, Germany. E-mail: hans.bastian{at}charite.de

OP0145 Induction therapy with adalimumab plus methotrexate versus methotrexate monotherapy in recent onset rheumatoid arthritis (RA) – an investigator initiated randomized controlled trial

Background To study the prolonged effect on disease activity by an early induction therapy with adalimumab (ADA) plus methotrexate (MTX) versus MTX alone in DMARD naïve patients (pts) with early RA (designated HIT HARD, funded by the German Ministry of Science). Methods In a double-blind randomized controlled trial, RA pts (disease duration of ≤12 months, ≥6 swollen, ≥6 tender joints, and CRP≥10 mg/l) were randomized into two groups: placebo (PBO) plus MTX (n=85), given s.c. at 15 mg/week (w) versus MTX 15 mg/w s.c. plus 40 mg ADA s.c. eow over 24w (n=87). After w24, both groups were treated only with MTX up to w48. The primary outcome measure was the DAS28-response at w48. Secondary outcomes was the pts in remission (DAS28<2.6), ACR responses, HAQ, SF36 and radiographic progression. Statistical analysis was based on the ITT population. To improve power, analysis of covariance (ANCOVA) with baseline (BL) status as covariable was applied to compare DAS28, HAQ between groups. Non-parametric ANCOVA was used to compare van der Heijde modified Sharp (Sharp vdH) scores. Multiple imputation method was used to replace missing data. Results Mean disease duration at BL was 1.7 years, 91 (53%) were ACPA positive and 114 (63%) IgM RF positive. DAS28 was 6.2±0.8 (ADA/MTX) and 6.3±0.9 (PBO/MTX) (p=0.60). Outcome parameters at w24 and w48 are presented in tables 1. During the induction phase, ADA/MTX reduced disease activity to a significantly greater extent than PBO/MTX (Table 1). After termination of ADA or PBO and continuation with MTX alone, the differences between both groups in clinical outcome parameters (DAS28, remission, ACR50 response, HAQ, SF36 mental score) decreased at w24/48 and did not reach statistical significance at w48. Nevertheless, combination therapy significantly reduced radiographic progression as demonstrated by the Sharp vdH erosion score (p=0.010) as compared to the combination group, joint space narrowing score (p=0.035) and Sharp vdH total score (p=0.003); Ratingen score (p=0.012) compared to MTX alone when analyzed after w48. Table 1. Comparison of clinical parameters at w 24 and w 48 Week 24 Week 48 Variable/Groups ADA/MTX PBO/MTX p ADA/MTX PBO/MTX p DAS28 3.0±1.2 3.6±1.4 0.009 3.2±1.4 3.4±1.6 0.41 Remission (%) 47.9 29.5 0.021 42.4 36.8 0.47 ACR50 (%) 63.8 48.7 0.049 52.6 51.4 0.88 ACR70 (%) 48.0 26.8 0.006 40.5 34.0 0.40 HAQ, mean±SD 0.49±0.6 0.72±0.6 0.0014 0.61±0.6 0.66±0.6 0.40 SF36 mental score, mean±SD 48.8±9.8 48.9±8.8 0.51 50.0±9.6 47.9±9.6 0.37 SF36 physical score, mean±SD 44.0±11.1 39.8±9.9 0.0002 41.4±12.4 42.0±10.3 0.79 Values are means and standard deviations if not otherwise specified. Conclusions Superiority in reduction of radiographic progression after initial combination therapy with ADA and MTX was seen at w 48, even after discontinuation of ADA treatment at w 24. Such a sustained effect was not found regarding the primary endpoint (DAS28 reduction). Disclosure of Interest J. Detert Grant/Research support from: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH, H. Bastian Speakers Bureau: Abbott & Co GmbH, J. Listing: None Declared, A. Weiss: None Declared, S. Wassenberg: None Declared, A. Liebhaber: None Declared, K. Rockwitz: None Declared, R. Alten: None Declared, K. Krüger: None Declared, R. Rau: None Declared, C. Simon: None Declared, E. Gremmelsbacher: None Declared, T. Braun: None Declared, B. Marsmann: None Declared, V. Höhne-Zimmer: None Declared, K. Egerer: None Declared, F. Buttgereit: None Declared, G.-R. Burmester Grant/Research support from: Abbott & Co GmbH, Consultant for: Abbott & Co GmbH, Speakers Bureau: Abbott & Co GmbH

Rheumatoide Arthritis: Diese Medikamente bremsen die Gelenkzerstörung

ZusammenfassungDie rheumatoide Arthritis ist die häufigste entzündlich-rheumatische Erkrankung. Unbehandelt führt sie zu progredienten und irreversiblen Gelenkdestruktionen. Da die Erkrankung in jedem Alter auftreten kann, ist sie sozioökonomisch bedeutsam. Für die Prognose ist die frühzeitige Diagnose und Therapieeinleitung entscheidend. Für die Diagnostik stehen, neben dem klinischen Befund, Laborparameter und bildgebende Verfahren (z. B. Röntgen, Sonographie und Magnetresonanztomographie) zur Verfügung. Therapeutisch sind ergo- und physiotherapeutischen Maßnahmen sowie vor allem eine individuelle, dem Krankheitsverlauf angepasste Medikation notwendig. Nichtsteroidale Antirheumatika wirken symptomatisch. Glukokortikoide sollten nach Möglichkeit nur kurzzeitig eingenommen werden. Als „disease-modifying antirheumatic drugs“ (DMARD, sog. Basistherapeutika) werden traditionell vor allem Methotrexat, Leflunomid, Sulfasalazin und seltener Hydroxychloroquin eingesetzt. Als neue gezielte Therapieansätze kommen Biologika zumeist in Kombination mit MTX zum Einsatz. Wichtige Substanzen sind Tumor-Nekrose-Faktor-α-Antagonisten, Abatacept, Rituximab und Tocilizumab. Ziel der Therapie ist eine anhaltende Krankheitsremission mit Verhinderung einer radiologischen Progression und Funktionserhalt.

Axiale Spondyloarthritis: aktuelle Therapie aus rheumatologischer Sicht

ZusammenfassungDie Therapieempfehlungen für die axialen Spondyloarthritiden haben sich in den vergangenen Jahren grundlegend verändert. Heute können wir zur Behandlung dieser potenziell schwer verlaufenden Erkrankungen auf eine Vielzahl moderner Medikamente zurückgreifen. Zur Standardtherapie gehören nach wie vor nichtsteroidale Antirheumatika. Wirken diese unzureichend, kommen Biologika zum Einsatz.