Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

OBJECTIVE: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA. METHODS: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36 months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12 months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy. CONCLUSIONS: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

Self-rated health in patients with rheumatoid arthritis is associated with health-related quality of life but not with clinical variables.

OBJECTIVES: Self-rated health (SRH) is a well-known overall health status measure used in the general population but it is rarely examined in a clinical setting. We assessed SRH-related factors in clinic-based patients with rheumatoid arthritis (RA). METHOD: The study included 123 consecutive outpatients treated in 1998-1999. Patient questionnaires, including a single SRH item, sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, and the Nottingham Health Profile (NHP) for health-related quality of life (QoL), were collected at baseline. Comorbidities were measured by the Charlson Comorbidity Index (CCI) and data on the use of drugs and surgery for RA were verified from medical records and by querying patients. Factors associated with SRH were examined using regression models with the propensity score as the covariate. Mortality rates were collected up to 31 December 2014. Hazard ratios (HRs) were used to estimate SRH-associated mortality. RESULTS: In univariate analysis, poor SRH was associated with higher age and poorer patient-reported outcomes (PROs) but not with gender and clinical variables. After adjustment for the propensity score, the NHP dimensions for pain, energy, emotional reactions, and mobility remained significantly associated with SRH. The age- and sex-adjusted HR for death was 2.38 [95% confidence interval (CI) 1.13-5.04, p = 0.034] for the patients with poor vs. good SRH. The propensity score-adjusted HR for death was 1.69 (95% CI 0.74-3.86, p = 0.21). Conclusions  In patients with RA, SRH was associated with health-related QoL dimensions, reflecting patients' well-being rather than clinical factors. During the 16 years of follow-up, SRH had no independent association with mortality.

Patients with rheumatoid arthritis have better functional and working ability but poorer general health and higher comorbidity rates today than in the late 1990s.

OBJECTIVES: Better treatment strategies and therapeutic options have changed the treatment of rheumatoid arthritis (RA) during the past decade. Our objective was to examine clinical and patient-reported outcomes in patients with RA treated in 1998-99 and 2011-12. METHOD: The cross-sectional observational study included 303 consecutive outpatients (n = 103 in 1998-99 and n = 200 in 2011-12) from the same outpatient clinic. Patient questionnaires included patients' sociodemographics, the Health Assessment Questionnaire (HAQ) for functional ability, the Nottingham Health Profile (NHP) for health-related quality of life (HRQoL), self-reported general health (GH), and operations performed due to RA. A clinical examination was conducted for all patients. Comorbidities according to the Charlson Comorbidity Index (CCI), anti-rheumatic drugs and medications were recorded and the HAQ and NHP dimensions calculated. The results from these two patient cohorts were compared. RESULTS: The cohorts were comparable with regard to age, sex, and RA duration while the patients in the 2011-12 cohort were less often seropositive for rheumatoid factor (RF), had a better socioeconomic situation, better functional and working ability, and a decreased rate of RA surgery. The patients in 2011-12 had higher comorbidities and poorer GH while the HRQoL dimensions did not differ between the cohorts except for better mobility in 2011-12. Methotrexate (MTX) and combinations of conventional anti-rheumatic drugs were more frequently used in 2011-12. Biologicals were used only in 2011-12. CONCLUSIONS: According to our results, more active anti-rheumatic therapy coincides with better RA-related outcomes. However, the result was the opposite with regard to overall health and comorbidities. Is this a new challenge in the treatment RA?

A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in outpatient specialty clinics in Finland.

OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.

Waist circumference based abdominal obesity may be helpful as a marker for unmet needs in patients with RA.

OBJECTIVES: To assess the impact of abdominal obesity (AO) on disease severity, cardiovascular risk factors, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA). METHOD: Two hundred and thirty consecutive outpatients were cross-sectionally assessed. Waist circumference (WC) with a cut-off point of ≥ 102 cm in men and ≥ 88 cm in women indicated AO. Clinical assessment included joint counts, radiographs of small joints, and laboratory tests. Comorbidities and medication were verified from the patients' database. Patient questionnaires included sociodemographics, pain intensity, global disease activity, the Beck Depression Inventory (BDI), the Health Assessment Questionnaire (HAQ), physical activity level, and the 36-item Short Form Health Survey (SF-36). Metabolic syndrome (MetS) was defined according to the criteria of National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III). The association of AO with the 28-joint count Disease Activity Score (DAS28) and mental (MCS) and physical component scores (PCS) of the SF-36 and the HAQ was assessed by using regression models with the propensity score as a covariate. RESULTS: The AO prevalence was 52% in the 200 eligible patients. In a univariate analysis, AO was associated with cardiovascular risk factors, low HAQ score, physical inactivity, disease activity parameters, impaired MCS, higher pain, and increased use of biological drugs and antidepressants. In a multivariable model, only poorer DAS28 (p = 0.018) and poorer HAQ score (p = 0.004) remained significantly associated with AO. CONCLUSIONS: AO is highly prevalent in patients with RA. In addition to cardiovascular risk factors, AO is associated with higher disease activity, higher disability, physical inactivity, more patients' perception of pain, and poorer mental health. Multifaceted promotion of lifestyle habits would be beneficial for improving AO-related health outcomes in patients with RA.

Positive treatment response improves the health-related quality of life of patients with early rheumatoid arthritis.

OBJECTIVE: To examine treatment induced changes in health-related quality of life (HR-QoL) in patients with early rheumatoid arthritis (RA). METHODS: Changes in HR-QoL were assessed by the Nottingham Health Profile (NHP) instrument in 62 consecutive working age patients with recent onset RA with duration of symptoms of less than two years and naive with regard to disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. Treatment-response was assessed by the criteria of the European League against Rheumatism (EULAR; 28-joint score; DAS28) at 6 months. RESULTS: NHP mean scores for pain (p=0.029) and emotional reaction (p=0.035) at baseline were related to EULAR response at 6 months, i.e. non-responders had the poorest baseline HR-QoL scores. When the patients were grouped according to EULAR response at 6 months there was a statistically significant mean linear change to better HR-QoL in NHP energy (p=0.0023), pain (p<0.001) and mobility (p=0.0085) from baseline to 6 months from the lowest to highest treatment-response level. CONCLUSION: Our results show that good treatment-response as measured by the EULAR response criteria translates into improved HR-QoL dimensions for energy, pain and mobility.

Nottingham health profile questionnaire incorporates important aspects of the patient perspective into outcome assessment in rheumatoid arthritis.

OBJECTIVE: There is a consensus on the need for a more thorough assessment of outcome of RA from the perspective of those who experience the disease. Our objective was to assess the health- related quality of life (HR-QOL) of RA patients by the Nottingham Health Profile (NHP), the measurement of subjective experienced distress. METHODS: One hundred and nineteen consecutive out-patients were cross-sectionally assessed. HR-QOL was evaluated by using the first section of the NHP, a generic quality of life instrument, that assess subjective distress on six dimensions: mobility, pain, energy, sleep, emotional reaction and social isolation. Functional capacity was measured by the Health Assessment Questionnaire (HAQ). RESULTS: The NHP scores for mobility, pain, energy and sleep showed a linear association (p<0.001 for each) with HAQ disability level. In addition to pain, patients with mild disability (HAQ 0-1) may suffer from remarkable fatigue (loss of energy) and problems in sleep. Even at the HAQ level 0, there was some perceived distress in almost all of the NHP dimensions. CONCLUSIONS: Poor HAQ levels were associated with patient perceived distress in dimensions which are getting minor attention in clinics, i.e., energy and sleep. It is to be noted that RA patients who reported no disability or its lowest levels measured by HAQ perceived notable distress in many NHP dimensions. Our results suggest that NHP is a potential candidate for a HR-QOL questionnaire which should considered to be used in routine clinical assessment of RA patients.

Life situation of spinal cord-injured persons in Central Finland.

STUDY DESIGN: Individual interview and questionnaire of a regional spinal cord-injured (SCI) population. OBJECTIVE: Local health care centres are mainly responsible for the SCI patients health care and rehabilitation after initial hospitalization in Finland. The purpose of the present study was to study aspects of the SCI patients life situation and their opinion of the health care services after 1 year since the injury. SETTING: Regional study in Central Finland. METHODS: Subjects were individually interviewed in their homes using a semi-structured questionnaire, the Functional Independence Measure (FIM) and the Beck Depression Inventory (BDI). RESULTS: The female/male ratio was 1:4. The mean age at the time of injury was 34 years in female and 40 in male. Traffic accidents accounted for 46% of the injuries. In all, 48 subjects (63%) used electrical or manual wheelchair or both. Most subjects regarded their living conditions as good having enough personal assistance in their everyday life. Only 10% of the subjects were employed. Half of the subjects had had out-patient physiotherapy, but no other therapies after 1 year since the injury. More than half of the subjects were dissatisfied with the current health care services. Many had experienced complications after the initial hospitalization, especially urinary tract infections, decubitus ulcers and neurogenic-type pain. FIM classified well according to the disability groups. The motor complete tetraplegic group had the lowest mean scores (63) and the recovered group the highest ones (122). There was no association between the FIM and the BDI results. There was a correlation between the BDI and the subject's age at the time of the injury and the year of the injury. The older the subjects were when injured, the higher were the BDI scores, that is, they had more depressive symptoms. Those injured in the 1990s had the highest BDI scores. Nearly one-third of the subjects had mild, moderate or severe depression. CONCLUSIONS: The reported medical complications, depression and dissatisfaction with the health care services support a life-long care for SCI patients in Jyväskylä Central hospital, not in the local health care centres. The psychological services, for example, prevention and treatment of depression, in particular, require more attention.

Validity of the Nottingham Health Profile in a Finnish out-patient population with rheumatoid arthritis.

OBJECTIVE: To assess the quality of life of 122 rheumatoid arthritis (RA) patients using the Nottingham Health Profile (NHP), which is a generic quality-of-life instrument, and to compare the results with those of 99 healthy local control subjects. METHODS: Our patient group represented consecutive out-patients from a central hospital. The NHP contains 38 items, each with a weighted score, that assess subjective distress on six dimensions: mobility, pain, energy, sleep, emotional reactions and social isolation. RESULTS: The median (age-adjusted) NHP scores for mobility, pain and energy showed statistically highly significant differences (P < 0.001) between the RA patients and the control group, indicating a poorer quality of life among the RA patients on all these dimensions. These NHP dimensions were also closely related to patients' experience of their overall health status. The NHP scores for sleep, emotional reaction and social isolation did not differ between the patients and the controls. CONCLUSION: The NHP, an instrument for assessing health-related quality of life, differentiated RA patients from local healthy individuals on the dimensions of mobility, energy and pain.

Epidemiology of central nervous system neoplasms. A regional survey in Central Finland.

An epidemiologic survey of central nervous system (CNS) neoplasms in Central Finland revealed a total of 367 neoplasms, 298 of which were diagnosed during 1975-82, the remaining being diagnosed earlier. Histological verification was available in 83% of intracranial and 90% of intraspinal neoplasms. 14% of the intracranial neoplasms diagnosed during 1975-82 were found incidentally at autopsy. Metastases corresponded to 18% of all CNS neoplasms. Age- and sex-adjusted annual incidence rates for primary and metastatic intracranial neoplasms were 12.3 and 3.4/100,000, and for intraspinal neoplasms 1.3 and 0.7/100,000, respectively. The total incidence of all CNS neoplasms was 17.7/100,000/year. Of the different types of intracranial neoplasms, meningiomas were more frequent among women than among men with a ratio of 8:1; metastases were more common among men with a ratio of 2.5:1. For primary intracranial neoplasms, point prevalences (January 1, 1983) were 65.9/100,000 and intraspinal neoplasms 9.1/100,000. The corresponding period prevalences for 1982 were 73.7 and 9.5/100,000.

Cerebral aspergillosis with special reference to cerebrospinal fluid findings.

A case of cerebral aspergillosis in a 69-year-old diabetic man is reported. The disease, initially presenting as headache and vertigo, was caused by Aspergillus fumigatus. Seven CSF specimens were examined. The main findings included decreased glucose and increased protein concentrations, leukocyte reaction and one positive culture for A. fumigatus. Neuropathological examination revealed granulomatous leptomeningitis and typical fungal hyphae. The process probably lasted for more than 1 year and was an important contributing factor to two brain stem infarcts.