This study in patients with rheumatoid arthritis (RA) treated with infliximab describes prospectively the course of (anti)infliximab levels within an infusion cycle to assess at what moment patients develop low/no infliximab trough levels and/or detectable anti-infliximab levels.Infliximab treated RA patients were included in this descriptive open-label cohort study. During one infusion cycle (anti-)infliximab levels were assessed just before and one hour after infusion, and subsequently at 50%, 75% and at the end of the infusion cycle (pre-infusion).27 patients were included. The median infliximab levels decreased from 77.0 mg/l (p25-p75: 65-89) one hour after the infusion to pre-infusion levels of 0.0 mg/l (p25-p75: 0.0-3.1). In 7 (26%) patients pre-infusion anti-infliximab antibodies were detected; these antibodies were already present halfway through the infusion cycle in 5 of the 7 individuals. Patients with detectable pre-infusion anti-infliximab antibodies have significantly more often low/no infliximab levels (< 1 mg/l) halfway trough the infusion cycle (in 5/7 patients) compared to patients without detectable pre-infusion anti-infliximab antibodies (0/20 patients, p < 0.001).Most anti-infliximab forming patients have detectable anti-infliximab antibodies halfway through an infusion cycle, which implies that these patients are exposed to nontherapeutical infliximab levels during more than half of their infusion cycle. As none of the patients without anti-infliximab antibodies had no/low-infliximab levels halfway through the infusion cycle, the presence of pre-infusion anti-infliximab antibodies seems a sensitive and specific predictor for no/low infliximab-levels.
To assess health care utilisation in Dutch patients with systemic sclerosis (SSc) and its associated factors. To evaluate patients' perspectives on quality of care and its association with health care use.In a cross-sectional design, 198 Dutch patients with SSc completed an anonymous survey concerning health care utilisation, quality of care (CQ Index), and quality of life (SF-36).In the last 12 months, 95% of the patients had contact with at least one medical specialist and two-thirds contacted at least one health professional (HP). The median numbers of visits to medical specialists and HPs were 7 and 7.5, respectively. Having a partner and reduced physical health status (SF-36 role-physical) were significantly associated with more visits to medical specialists and HPs. The median numbers of disciplines contacted since the onset of SSc and in the last 12 months were 8 and 4, respectively. Patients with less fatigue (SF-36 vitality) and more pain (SF-36 bodily pain) contacted more disciplines. A higher number of disciplines involved in the care was significantly associated with less satisfaction with the coordination of care (r=-0.14, p=0.03).Health care utilisation in Dutch patients with SSc is substantial, as is reflected in the high number of visits and the number of disciplines. Patients' rating of care coordination was lower if more disciplines were involved in their care.
Systemic sclerosis (SSc) patients are at risk for organ involvement and premature death. The occurrence of organ involvement that is reported differs widely between various long term cohort studies; ILD 25–90%, PAH 8–32%, CI 5–30%, and SRC 4–12%. Differences in findings also apply to survival, the 5- and 10-year survival rates between studies vary from 80% to 90% and from 60% to 85% respectively (1–3).
Objectives
To assess the occurrence of organ involvement and death in a large, unselected cohort of Dutch SSc patients at the moment of diagnosis and during 5 years of follow-up, stratified by disease subtype and auto-antibodies.
Methods
Up to 2015, 690 SSc patients were included in the Nijmegen SSc cohort. Occurrence of interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac involvement (CI), scleroderma renal crisis (SRC) and occurrence of death were determined using survival analysis, stratified by disease subtype (limited cutaneous SSc and diffuse cutaneous SSc) and auto-antibodies (ACA, ATA, anti-RNP).
Results
Organ involvement was already present at SSc diagnosis in 32% of patients. In 25%, organ involvement developed during follow-up, mostly ILD (22%). Significant differences between lcSSc and dcSSc were found in SRC at baseline and ILD, PAH and SRC during follow-up. Between the autoantibody subgroups, the occurrence of ILD, PAH and SRC at baseline and ILD during follow-up differed. There were no differences in survival between subtypes and auto-antibodies. The overall 5-year survival rate was 89%. Patients without organ involvement at SSc diagnosis had a better 5-year survival rate than patients with organ involvement at SSc diagnosis: 95% versus 73% respectively (p<0.001). (figure 1)
Conclusions
In many SSc patients, organ involvement is already present at diagnosis or develops in the first 5 years after diagnosis. Survival is significantly worse in patients who already have involvement at the moment of SSc diagnosis.
References
Muangchan C, Canadian Scleroderma Research G, Baron M, Pope J. The 15% rule in scleroderma: the frequency of severe organ complications in systemic sclerosis. A systematic review. The Journal of rheumatology. 2013;40(9):1545–56. Vonk MC, Broers BM, Heijdra YF, Ton E, Snijders R, van Dijk AP, et al. Systemic sclerosis and its pulmonary complications in the Netherlands An epidemiological study. AnnRheumDis. 2008. Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis & rheumatology. 2014;66(6):1625–35.
Organ involvement in systemic sclerosis (SSc) is tightly linked to survival, which is decreased in both limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc). Early organ involvement occurs often in the first years of the disease, mainly in dcSSc (1). In the context of new emerging therapies, recognition of SSc patients prone to early organ involvement at clinical diagnosis is important. Various studies describe the occurrence of organ involvement. However, there are only a few studies in recently diagnosed SSc patients describing organ involvement at and after clinical diagnosis (2). Therefore, we want to address recent data on occurrence of organ involvement in SSc patients at the moment of diagnosis and during 5 years of follow-up.
Objectives
To determine the occurrence of lung, cardiac and renal involvement at diagnosis and during 5 years of follow-up in patients with lcSSc and dcSSc
Methods
The Nijmegen Systemic Sclerosis inception cohort consisted of 619 SSc patients clinically diagnosed and classified as either dcSSc or lcSSc based on skin involvement. Data on interstitial lung disease (ILD), pulmonary hypertension (PH), scleroderma renal crisis (SRC) and cardiac involvement were collected from diagnosis up to 5 years of follow-up. ILD: high-resolution CT anomalies in combination with lung function abnormalities. PH: confirmed by right heart catheterization with a mean pulmonary artery pressure of ≥25 mmHg and a pulmonary capillairy wedge pressure ≤15 mmHg. SRC: new-onset hypertension >150/85 mmHg and a decrease in eGFR of ≥30%. Cardiac involvement: ejection fraction <50% and/or left ventricular diastolic dysfunction >grade 1 and/or symptomatic pericard effusion. Kaplan Meier Curves and Log Rank tests were used for analysis.
Results
The 415 patients in this study included fewer males in the lcSSc subgroup (27% vs. 47%, p<0.001), and time between the first non-Raynaud symptom and diagnosis was longer (16 vs. 8 months, p<0.001) compared to the dcSSc subgroup. Presence of ILD at diagnosis did not differ between lcSSc and dcSSc (both 19%). In lcSSc, PH was present at diagnosis in 9% compared to 4% in dcSSc (p=0.08). Presence of SRC at diagnosis was less frequent in lcSSc compared to dcSSc (0% vs. 4%, p=0.009). In 3% of lcSSc cardiac involvement at diagnosis was present compared to 4% in dcSSc (p=0.34). Median time from diagnosis to development of ILD, PH, SRC and cardiac involvement did not differ between lcSSc and dcSSc. The figures show development of organ involvement during the 5-year follow up, with differences between lcSSc and dcSSc (p<0.001 in ILD, p=0.26 in PH, p=0.004 in both SRC and cardiac involvement).
Conclusions
Identification of patients at risk for early organ involvement is an important goal. Our data show occurrence of organ involvement in lcSSc and dcSSc at the moment of diagnosis and during 5-years of follow-up. This supplies us with a first key step in the development of a prediction model for early organ involvement at the moment of diagnosis.
References
Steen VD, Medsger TA, Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000;43(11):2437-44. Epub 2000/11/18. Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, et al. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014;66(6):1625-35. Epub 2014/03/05.
