Long-term outcome is better when a methotrexate-based treatment strategy is combined with 10 mg prednisone daily: follow-up after the second Computer-Assisted Management in Early Rheumatoid Arthritis trial.

OBJECTIVES: In the second Computer-Assisted Management in Early Rheumatoid Arthritis trial, patients had started with methotrexate and 10 mg prednisone (MTX+pred) or placebo (MTX+plac). After the trial, prednisone was tapered and stopped, if possible. The objective was to compare, during the post-trial follow-up between the two former strategy groups, initiation of the first biological disease-modifying antirheumatic drug (bDMARD), radiographic outcome and onset of glucocorticoid (GC)-related comorbidities. METHODS: Data on prednisone and bDMARD use and onset of GC-related comorbidities were collected retrospectively. Sharp/van der Heijde scoring was performed. Data were analysed using Fisher's exact and Mann-Whitney U tests. RESULTS: Of 218 patients post-trial follow-up data were available. The maximum follow-up time was 11.8 years. Fewer patients initiated a first bDMARD in the former MTX+pred compared with the former MTX+plac strategy group: 31% vs 50%, p=0.003. At the 2 year post-trial follow-up, the median erosion score was significantly lower in the former MTX+pred versus former MTX+plac strategy group: 0 (range 0-0) versus 0 (0-2), p=0.002. No significant differences between the former strategy groups in the onset of GC-related comorbidities during the post-trial follow-up were found. CONCLUSION: Addition of 10 mg prednisone daily to an MTX-based treatment strategy in early rheumatoid arthritis results in a lower initiation rate of a first bDMARD and significantly better radiographic outcomes, yet does not result in more GC-related comorbidities.

Patient-reported disease-specific quality-of-life and symptom severity in systemic mastocytosis.

BACKGROUND: Presently, no validated data exist on symptom severity and disease-specific quality-of-life (QoL) for patients with mastocytosis. Simultaneously, clinical trials and drug application processes increasingly mandate reporting patients' perspectives on symptoms and QoL. We report on the development and validation of the mastocytosis quality-of-life questionnaire (MQLQ) and the mastocytosis symptom assessment form (MSAF). METHODS: Both outcome measures were developed in a standardized stepwise method, starting with the identification of items in focus groups (n = 12), item reduction and subsequent cross-sectional validation in a 63% female cohort of 164 adult patients with indolent systemic mastocytosis. RESULTS: The MSAF reveals that fatigue is the severest mastocytosis symptom while the MQLQ indicates that fear of anaphylaxis mostly impacts QoL. Cross-sectional validity was assessed by correlating both individual domains and the total scores of the MQLQ and MSAF with independent measures of mastocytosis. The total scores of both the MQLQ (P < 0.001; Spearman's r: 0.568) and the MSAF (P < 0.001; Spearman's r: 0.559) correlated significantly with the consensus on physician-scored mediator symptoms. The MQLQ domains displayed a high internal consistency (Cronbach's alpha: 0.841-0.958) and the domains 'bones', 'skin symptoms' and 'anaphylaxis' differed significantly between patients with and without osteoporosis, urticaria pigmentosa or anaphylaxis, respectively (P < 0.001). CONCLUSIONS: The MQLQ is the first disease-specific QoL questionnaire for mastocytosis and is complemented by the MSAF, a short and convenient symptom scoring form. Both patient-reported outcome measures are valid, reliable and discriminate between patients with different disease characteristics, making them useful instruments for clinical research.

Efficacy and safety of selective glucocorticoid receptor modulators in comparison to glucocorticoids in arthritis, a systematic review.

BACKGROUND: Long-term treatment with glucocorticoids (GCs) plays an important role in the management of arthritis patients, although the efficacy/safety balance is unfavorable. Alternatives with less (severe) adverse effects but with good efficacy are needed. Selective GC receptor modulators (SGRMs) are designed to engage the GC receptor with dissociative characteristics: transactivation of genes, which is mainly responsible for unwanted effects, is less strong while trans-repression of genes, reducing inflammation, is maintained. It is expected that SGRMs thus have a better efficacy/safety balance than GCs. A systematic review providing an overview of the evidence in arthritis is lacking. OBJECTIVE: To systematically review the current literature on efficacy and safety of oral SGRMs in comparison to GCs in arthritis. METHODS: A search was performed in Medline, Embase and the Cochrane Library, from inception dates of databases until May 2017. Experimental studies involving animal arthritis models or human material of arthritis patients, as well as clinical studies in arthritis patients were included, provided they reported original data. All types of arthritis were included. Data was extracted on the SGRM studied and on the GC used as reference standard; the design or setting of the study was extracted as well as the efficacy and safety results. RESULTS: A total of 207 articles was retrieved of which 17 articles were eligible for our analysis. Two studies concerned randomized controlled trials (RCT), five studies were pre-clinical studies using human material, and 10 studies involved pre-clinical animal models (acute and/or chronic arthritis induced in mice or rats). PF-04171327, the only compound investigated in a clinical trial setting, had a better efficacy/safety balance compared to GCs: better clinical anti-inflammatory efficacy and similar safety. CONCLUSION: Studies assessing both efficacy and safety of SGRMs are scarce. There is limited evidence for dissociation of anti-inflammatory and metabolic effects of the SGRMs studied. Development of many SGRMs is haltered in a preclinical phase. One SGRM showed a better clinical efficacy/safety balance.