Endpoints: consensus recommendations from OMERACT IV. Outcome Measures in Rheumatology

The goal of the 'Outcome Measures in Rheumatology' (OMERACT) process is to select domains and/or outcome measures for clinical trials in each defined disease category according to truth, discrimination and feasibility. OMERACT IV, held in Cancun, Mexico, April 1998, included the module 'Systemic Lupus Erythematosus (SLE)', designed to define a preliminary core set of outcome domains for randomized controlled trials and longitudinal observational studies (LOS). Although specific measures to be used in clinical trials of SLE have yet to be determined, both randomized controlled trials and longitudinal observation studies groups recommended that outcome be assessed in terms of disease activity and damage in all organ systems involved, as well as by health related quality of life, meaningful to patients, and adverse events. These recommendations were ratified by the majority of participants. In a heterogeneous patient population such as SLE, it is recognized that any individual measure of clinical response may reflect only a portion of what might be termed the 'true outcome'. A responder index could integrate such relatively independent measures of outcome into a single assessment, potentially increasing statistical power and decreasing sample size. Results from randomized controlled trials currently underway assessing these outcome domains are eagerly awaited, and are expected to rapidly advance the field.     

A randomised controlled trial of a care home rehabilitation service to reduce long-term institutionalisation for elderly people

OBJECTIVES: to evaluate the effect of a care home rehabilitation service on institutionalisation, health outcomes and service use. DESIGN: randomised controlled trial, stratified by Barthel ADL index, social service sector and whether living alone. The intervention was a rehabilitation service based in Social Services old people's homes in Nottingham, UK. The control group received usual health and social care. PARTICIPANTS: 165 elderly and disabled hospitalised patients who wished to go home but were at high risk of institutionalisation (81 intervention, 84 control). MAIN OUTCOME MEASURES: institutionalisation rates, Barthel ADL index, Nottingham Extended ADL score, General Health Questionnaire (12 item version) at 3 and 12 months, Health and Social Service resource use. RESULTS: the number of participants institutionalised was similar at 3 months (relative risk 1.04, 95% confidence intervals 0.65-1.65) and 12 months (relative risk 1.23, 95% confidence intervals 0.75-2.02). Barthel ADL Index, Nottingham Extended ADL score and General Health Questionnaire scores were similar at 3 and 12 months. The intervention group spent significantly fewer days in hospital over 3 and 12 months (mean reduction 12.1 and 27.6 days respectively, P < 0.01), but spent a mean of 36 days in a care home rehabilitation service facility. CONCLUSIONS: this service did not reduce institutionalisation, but diverted patients from the hospital to social services sector without major effects on activity levels or well-being.     

Pulmonary hypertension in systemic lupus erythematosus

The occurrence of pulmonary hypertension in systemic lupus erythematosus (SLE) has been rarely reported. To date only 18 well documented cases of SLE with pulmonary hypertension have been published. We review the literature on pulmonary hypertension in SLE, and add the case of a young woman with a recent onset of both SLE and pulmonary hypertension. Hemodynamic studies were carried out before and during treatment with nifedipine and hydralazine alone and in combination. Despite improvement in pulmonary vascular resistance, pulmonary pressures were unaffected by the drugs, although our patient had symptomatic relief.     

Fibromyalgia in human immunodeficiency virus infection

Tenderness was assessed by point count and by scored palpation in 51 patients with human immunodeficiency virus (HIV) infection as well as 51 patients with rheumatoid arthritis (RA) and 50 patients with psoriatic arthritis (PsA). Fifteen of 51 (29%) patients with HIV infection met criteria for fibromyalgia, based on the presence of 10 tender (of 14) "fibrositic" points. Similar results were observed among patients with PsA (24%). The prevalence of fibromyalgia was higher among patients with RA (57%). Patients with HIV and PsA were less tender than patients with RA. Fibromyalgia in patients with HIV was significantly associated with myalgia and arthralgia, but not with age, duration of HIV infection, stage of HIV disease, or zidovudine therapy.     

Association of nuclear factor-kappaB in psoriatic arthritis

OBJECTIVE: To examine the association of single nucleotide polymorphisms (SNP) in the NFKB1 gene, as well as 2 genes in the nuclear factor (NF)-kappaB functional complex (RelA and NFKBIA), in patients with psoriatic arthritis (PsA) from Newfoundland. METHODS: Patients with PsA and controls were genotyped for one 4-base insertion/deletion and 5 SNP in NFKB1, 4 SNP in RelA, and 7 SNP in NFKBIA by time-of-flight mass spectrometry, using the Sequenom platform. Chi-square analysis was used to test the single locus associations between SNP in the NF-kappaB complex and PsA. Associations between multi-locus haplotypes and case or control status were tested using the software PHASE. RESULTS: Two hundred and twenty-four patients with PsA (52% male) and 88 ethnically matched controls (64% male) were genotyped. No association was noted with any of the SNP tested for the single locus associations in NFKB1, RelA, and NFKBIA or with multi-locus haplotypes. In particular, the allele frequency for the NFKB1 -94delATTG was 41.7% in cases and 41.6% in the controls (p = 0.97). CONCLUSION: No association between the NFKB1 -94 ins/delATTG promoter polymorphism or with other NF-kappaB complex SNP in patients with PsA from Newfoundland was observed.     

Serial renal biopsy in systemic lupus erythematosus

OBJECTIVE: To examine the role of sequential renal biopsies in patients with systemic lupus erythematosus (SLE), with regard to indications, morphologic change over time, and the clinical utility of repeat biopsies. METHODS: Patients with repeat renal biopsies were identified from the University of Toronto Lupus Clinic Database and their biopsies were reviewed blindly by a committee, using the WHO classification as well as activity and chronicity indices. Reasons for obtaining biopsy were documented, and therapeutic decisions following repeat biopsy were tabulated. RESULTS: Fifty-seven patients (49 F/9 M) had at least 2 renal biopsies between 1970 and 1994. The mean interval between biopsies was 4.2 years. The major reason for obtaining the first biopsy was disease diagnosis (32/57), while the majority of repeat biopsies were performed to discern the cause of increasing proteinuria (45/57). A comparison of the WHO classification of initial and repeat biopsies showed evolution to another class in 23 instances, but more commonly a change within a class was seen. A decrease in proliferative lesions (classes III and IV and subsets of V) was noted on repeat biopsies. The chronicity index increased significantly (p = 0.0001) and the activity index decreased (p = 0.064) between biopsies. Seventy-seven percent of patients had a change in treatment based on biopsy results. CONCLUSION: The major reason for repeat renal biopsy in patients with SLE was proteinuria. Renal morphology in patients with SLE can change with time, particularly in terms of chronicity and activity features. Repeat biopsies in patients with SLE appear to have clinical utility.     

HLA-D region genes and rheumatoid arthritis (RA): importance of DR and DQ genes in conferring susceptibility to RA.

The distribution of HLA-D region antigens was studied in three groups (I, IIa, and IIb) of patients with rheumatoid arthritis (RA): group I comprised 43 patients with mild, non-progressive RA, controlled by non-steroidal anti-inflammatory drugs without progression or erosions; group II comprised 94 patients with severe disease, who had earlier been treated with non-steroidal anti-inflammatory drugs and all had incomplete response requiring treatment with gold (sodium aurothiomalate). Of these, 46 patients (group IIa) responded to gold and the disease was well controlled, and the remaining 48 patients (group IIb) did not respond to gold and developed gold induced toxic reactions, including thrombocytopenia or proteinuria, or both. HLA-D region antigens were defined by serological and molecular (Southern blot analysis and oligonucleotide typing) techniques. The results show that DR4 was significantly increased in all three groups of patients. The prevalence of DR1, or DR1 in DR4 negative patients, and DR3 and DR4 associated DQw7 specificities, however, showed differences in these three groups of patients. The prevalence of DR1 and of DR1 in DR4 negative patients was increased only in patients with mild (group I) RA, but not in patients with severe (groups IIa and IIb) disease. On the other hand, the prevalence of DR4 associated DQw7 was significantly increased in patients with severe disease, but not in patients with mild RA. In addition, DR3 was significantly increased only in patients with severe disease who developed gold induced toxic reactions (group IIb). These data suggest that the HLA-D region genes which cause susceptibility to mild RA may be different from those causing susceptibility to severe RA. The results suggest that both DR and DQ (A, B) genes may be important in conferring susceptibility to RA: DR in mild disease and DQ in severe RA.     

Consensus exercise on domains in psoriatic arthritis

Recent studies with biological therapy in psoriatic arthritis (PsA) have highlighted the need for validated and widely accepted assessment tools and outcome measures for this disease. A Delphi process was established through the CASPAR group where domains for assessment of PsA in clinical trials, longitudinal studies, and rehabilitation were identified. Although the process reduced the list of possible domains to approximately 12, it was not able to detect those that would be most important. Moreover, skin assessment was left out. A further study through the GRAPPA group subsequently identified the following domains: inflammation (peripheral joints, axial skeleton, physician global assessment), other features (dactylitis, enthesitis), skin and nails, imaging, biomarkers, and patient derived indices (pain, quality of life, itch, function), as important in the assessment of patients with PsA. These domains require further refining, and instruments to measure the items need to be developed.