Accompanying the increased use of biologic and non-biologic antirheumatic agents, patients with RA have been exposed to an increased risk of Pneumocystis jirovecii infection, which causes acute fulminant P. jirovecii pneumonia (PCP). Mortality in this population is higher than in HIV-infected individuals. Several guidelines and recommendations for HIV-infected individuals are available; however, such guidelines for RA patients remain less clear. Between 2006 and 2008 we encountered a clustering event of P. jirovecii infection among RA outpatients. Through our experience with this outbreak and a review of the recent medical literature regarding asymptomatic colonization and its clinical significance, transmission modes of infection and prophylaxis of PCP, we have learned the following lessons: PCP outbreaks among RA patients can occur through person-to-person transmission in outpatient facilities; asymptomatic carriers serve as reservoirs and sources of infection; and short-term prophylaxis for eradication of P. jirovecii is effective in controlling PCP outbreaks among RA outpatients.
To compare persistence and adherence to triple therapy with nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor plus MTX (TNFi+MTX) in patients with rheumatoid arthritis (RA).
OBJECTIVES:Mesalamine non-adherence is common among patients with ulcerative colitis (UC), and can be difficult to identify in practice. We sought to determine whether a random urine test for salicylates could be used as a marker of 5-aminosalicylic acid (5-ASA) ingestion and identify patients at risk of non-adherence. Our aim is to determine whether measurement of salicylates in a random urine sample correlates with 5-ASA levels, and predicts an individual’s risk of mesalamine non-adherence.METHODS:Prospective observational study. Urinary salicylates (by colorimetry) and 5-ASA (by liquid chromatography and tandem-mass spectrometry) were measured in a random urine sample at baseline in patients and controls. Mesalamine adherence was quantified by patient self-reports at enrollment and pharmacy refills of mesalamine over 6 months.RESULTS:A total of 93 patients with UC taking mesalamine maintenance therapy were prospectively enrolled from the clinic. Random urine salicylate levels (by colorimetry) were highly correlated with urine 5-ASA metabolite levels (by mass spectrometry; R2=0.9). A random urine salicylate level above 15 mg/dl distinguished patients who had recently taken mesalamine from controls (area under the curve value 0.9, sensitivity 95%, specificity 77%). A significant proportion of patients (27%) who self-identified as “high adherers” by an adherence questionnaire (Morisky Medication Adherence Scale-8) had random levels of urine salicylate below this threshold. These patients were at higher risk of objectively measured non-adherence to mesalamine over the subsequent 6 months (RR: 2.7, 95% CI: 1.1-7.0).CONCLUSIONS:A random urine salicylate level measured in the clinic can identify patients who have not recently taken mesalamine, and who are at higher risk of longitudinal non-adherence. This test could be used to screen patients who may warrant interventions to improve adherence and prevent disease relapse.Am J Gastroenterol advance online publication, 8 January 2013; doi:10.1038/ajg.2012.419.
5-Aminosalicylic acid (5-ASA) is a first-line therapy for inducing and maintaining remission of mild and moderately active ulcerative colitis (UC). When the proximal margin of inflammation is distal to the splenic flexure, 5-ASA therapy can be delivered as a rectal suppository, foam or liquid enema.
We systematically reviewed and compared the efficacy and safety of oral mesalamine formulations (sustained release, delayed release, and prodrugs) used for induction and maintenance of remission in ulcerative colitis. The main objective of this review was to determine if there are any differences in efficacy or safety among the oral 5-ASA drugs.
Medications for rheumatoid arthritis (RA) may affect survival. However, studies often include limited follow-up and do not account for selection bias in treatment allocation. Using a large longitudinal database, we examined the association between prednisone use and mortality in RA, and whether this risk was modified with concomitant disease-modifying antirheumatic drug (DMARD) use, after controlling for propensity for treatment with prednisone and individual DMARDs.
Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial.
Non-adherence to disease-modifying antirheumatic drugs (DMARDs) hampers the targets of rheumatoid arthritis (RA) treatment, obtaining low disease activity and decreasing radiological progression. This study investigates if, and to what extent, non-adherence to treatment would lead to a higher 28-joint count disease activity score (DAS28) in the first year after diagnosis.
OBJECTIVES: To evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission. METHODS: GO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28-ESR remission was measured. RESULTS: 3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28-ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population. CONCLUSIONS: Add-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.