Economic considerations and patients' preferences affect treatment selection for patients with rheumatoid arthritis: a discrete choice experiment among European rheumatologists.

OBJECTIVE: To compare the value that rheumatologists across Europe attach to patients' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis. METHODS: In a discrete choice experiment, European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity. Treatments differed in five attributes: efficacy (improvement and achieved state on disease activity), safety (probability of serious adverse events), patient's preference (level of agreement), medication costs and cost-effectiveness (incremental cost-effectiveness ratio (ICER)). A Bayesian efficient design defined 14 choice sets, and a random parameter logit model was used to estimate relative preferences for rheumatologists across countries. Cluster analyses and latent class models were applied to understand preference patterns across countries and among individual rheumatologists. RESULTS: Responses of 559 rheumatologists from 12 European countries were included in the analysis (49% females, mean age 48 years). In all countries, efficacy dominated treatment decisions followed by economic considerations and patients' preferences. Across countries, rheumatologists avoided selecting a treatment that patients disliked. Latent class models revealed four respondent profiles: one traded off all attributes except safety, and the remaining three classes disregarded ICER. Among individual rheumatologists, 57% disregarded ICER and these were more likely from Italy, Romania, Portugal or France, whereas 43% disregarded uncommon/rare side effects and were more likely from Belgium, Germany, Hungary, the Netherlands, Norway, Spain, Sweden or UK. CONCLUSIONS: Overall, European rheumatologists are willing to trade between treatment efficacy, patients' treatment preferences and economic considerations. However, the degree of trade-off differs between countries and among individuals.

Influence of biologic therapy on return to work in people with work disability due to ankylosing spondylitis.

OBJECTIVE: To answer the question 'does TNF blockade therapy enable people with severe AS to return to work or work more productively?'. METHODS: All patients with AS currently receiving anti-TNF therapy at two UK Hospitals were asked to complete a questionnaire. This asked about occupational history, type of work, degree of job-related physical activity, working hours and sickness absence from work both currently (on anti-TNF treatment) and pre-treatment. RESULTS: Sixty-five patients (72.3% male), aged 29-64 (mean 46.1) yrs, whose duration of anti-TNF treatment ranged from 3 to 56 (mean 19.1) months were studied. Twenty-four (36.9%) patients were receiving infliximab, 21 (32.3%) etanercept and 20 (30.8%) adalimumab. Pre-treatment, 46 (70.8%) were in employment (1 was a student); 38 (58.5%) were working full-time and 8 (12.3%) part-time; 19 (29.2%) were not working. On treatment, 50 (76.9%) patients were working, 44 (67.7%) full-time and 6 (9.2%) part-time. Two individuals who worked part-time pre-treatment had returned to work full-time. Thus, on treatment, 4 of the 19 patients who were previously unable to work returned to employment, and 2 others increased their work from part-time to full-time. Patients rated the effect of AS on work capacity as 7.05/10 pre-treatment and 2.92/10 post-treatment. Those who were working lost, on average, 15 days from work due to sick leave in the 12 months pre-treatment and 0.91 days in the first 12 months on treatment. CONCLUSIONS: Treatment of active AS with TNF blockade appears to be associated with improved capacity for work.

Assessment of the impact of flares in ankylosing spondylitis disease activity using the Flare Illustration.

OBJECTIVES: Many AS patients report periods of perceived higher disease activity (flares). This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures. METHODS: Consecutive AS patients (n = 114) were asked whether they experience flares, and if they experience symptoms of AS between flares. They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease (i) since symptom onset and (ii) in the past year. Associations between reported disease pattern and disease activity (Bath AS Disease Activity Index, BASDAI); functional impairment (Bath AS Functional Index, BASFI); AS Quality of Life (ASQoL); Back Pain (Nocturnal and Overall) and demographic features were assessed in a subsample (n = 83) (statistical significance defined at P 70% of patients) and patterns with constant symptoms since onset (vs intermittent symptoms) were associated with worse health status (ASQoL: P = 0.007; BASDAI: P = 0.029; BASFI: P = 0.013, overall back pain: P = 0.025). CONCLUSIONS: Almost all AS patients report flares in disease activity: 70-80% report constant symptoms with single/repeated flares, while 20-30% report flares with no intermittent symptoms. The former is associated with a significantly poorer health status. These findings will be validated in a prospective study.

When is arthritis reactive?

Reactive arthritis is an important cause of lower limb oligoarthritis, mainly in young adults. It is one of the spondyloarthropathy family; it is distinguishable from other forms of inflammatory arthritis by virtue of the distribution of affected sites and the high prevalence of characteristic extra-articular lesions. Many terms have been used to refer to this and related forms of arthritis leading to some confusion. Reactive arthritis is precipitated by an infection at a distant site and genetic susceptibility is marked by possession of the HLA-B27 gene, although the mechanism remains uncertain. Diagnosis is a two stage process and requires demonstration of a temporal link with a recognised "trigger" infection. The identification and management of "sexually acquired" and "enteric" forms of reactive arthritis are considered. Putative links with HIV infection are also discussed. The clinical features, approach to investigation, diagnosis, and management of reactive arthritis are reviewed.

Reiter's syndrome and reactive arthritis: a current view.

This paper reviews advances in the understanding of the pathogenesis of reactive arthritis that have occurred over the last decade. Inflammatory aseptic joint disease has been linked with prior infection initiated by many different species of microorganisms. The presence of intra-articular bacterial antigens has now been firmly established with the demonstration of bacteria, bacterial fragments, DNA, RNA, and bacterial lipopolysaccharide in joints of patients with reactive arthritis. Chlamydia trachomatis, Salmonella enteritidis, and Shigella flexneri have all been detected in the joint by immunological techniques, although there is still some doubt as to the form in which they reach the joint and whether or not they persist. A number of phlogistic bacterial components could be acting as arthritogens. Negative joint culture results from patients with reactive arthritis make it unlikely that bacteria in the joint are viable, although chlamydial DNA has been shown in the joints of patients with sexually acquired reactive arthritis using the polymerase chain reaction. The use of antimicrobial therapy in the treatment of reactive arthritis is under review; data suggests that long-term antibiotic treatment warrants further study. The role of HLA-B27 in disease pathogenesis is discussed as are possible mechanisms of interplay between germ and gene. HLA-B27 might confer disease susceptibility by affecting immune mechanisms other than classical antigen presentation. The immunopathogenesis of joint inflammation in reactive arthritis is explored with reference to studies of humoral and cellular immune responses. Serological evidence to support the concept of molecular mimicry is far from conclusive; the results of relevant studies are summarized. Lymphocyte proliferation experiments suggest that antigen presenting cells play an important role. Finally, our views on reactive arthritis in the 1990s, and areas of new and potentially fruitful future research are presented.

Reiter's syndrome and associated arthritides.

Several distinct arthritic syndromes now have been recognized in HIV-infected persons. These comprise seronegative spondarthritis, including classic Reiter's syndrome and psoriatic arthritis associated with HLA-B27, and undifferentiated arthritis usually confined to the lower limbs, unassociated with other lesions, and unrelated to any known genetic marker. In such cases great care should be taken to exclude infection. In addition, a syndrome of short-lived but sometimes severe arthralgias also occurs. Spinal pain is a major problem in some patients but ankylosing spondylitis appears to be rare among this group. Psoriasis probably occurs more often in the HIV-infected group than in the population in general and may be especially severe in those patients with arthritis. Arthritis has been reported in the United States, Europe, and Africa among persons considered to be at high and low risk for HIV infection. Arthritis can occur at any stage of HIV infection, but the true prevalence of arthritic syndromes and the nature of their association with HIV infection remains unclear. In view of the development of Reiter's syndrome in some patients, precipitating bacterial infections have been sought as the culprits. In a minority of cases, shigella, yersinia, and campylobacter infections have been implicated, but in the majority of cases, no specific infection has been identified. In most patients depletion of circulating CD4-positive lymphocytes is present by the time that arthritis is detected, but only limited data on synovial immunopathology are available. In some patients changes of nonspecific chronic synovial inflammation are present and synovial fluid cell counts are high. In other patients evidence of inflammatory changes is minimal. Human immunodeficiency virus has been isolated from joint fluid and identified in large mononuclear, probably dendritic, cells and lymphocytes. Synovium from patients dying with AIDS but with apparently normal joints also shows significant abnormalities that could lead to joint disease in long-term survivors. The possibility of a viral etiology of arthritis in some cases is suggested by the induction of arthritis in animals by lentivirus infection; it also is possible, however, that HIV enhances the effect of mechanisms that can operate in the absence of HIV infection. Conventional treatments of rheumatic lesions, including intraarticular steroids, appear to be safe and reasonably effective. Anecdotal evidence suggests that treatment with methotrexate and azathioprine leads to exacerbation of HIV disease and should be avoided.

Sexually transmitted arthritis syndromes.

Sexually transmitted infections may provoke a wide variety of rheumatic lesions. Disseminated N. gonorrhoeae infection leads to septic arthritis, which may be rapidly destructive but which responds promptly to appropriate antibiotic therapy. In contrast, both gonococcal and nongonococcal infections may lead to aseptic "reactive" arthritis or Reiter's syndrome. Inheritance of HLA B27 confers a relative risk of 30 to 50 times for the development of this condition. The demonstration of C. trachomatis antigen in joint material from a minority of patients suggests that direct interaction between microbial components and class I HLA antigens in the joint may be central to the pathogenesis of this disease. Arthralgia and arthritis occur in up to 50% of individuals in the prodrome of hepatitis B infection. Joint symptoms may be accompanied by urticarial or cutaneous vasculitic lesions, especially on the legs; both features resolve with the onset of jaundice. Hepatitis B infection is also a major cause of necrotizing vasculitis, which may or may not be associated with overt hepatitis. Seronegative arthritis, including Reiter's syndrome, psoriatic arthritis, and undifferentiated arthritis, a Sjögren's-like syndrome, vasculitis, and myopathies have been described in association with HIV infection. It is clear that synovitis occurs in those patients despite the fact that HIV is present in immune cells within the joint during inflammatory arthritis and that both antigen presentation and lymphocyte responsiveness within the joint are impaired. Nevertheless, synovitis may occur in the presence of marked CD4-positive lymphocyte depletion. Rheumatic syndromes, including arthralgia, inflammatory arthritis, and neuropathic arthritis, may occur during any stage of congenital or acquired syphilis. Syphilitic synovitis responds well to antibiotic therapy, but neuropathic lesions cannot be treated effectively. Septic arthritis has rarely been described as a complication of disseminated Mycoplasma or Urea-plasma infections, and joint lesions sometimes associated with erythema nodosum have also been reported in lymphogranuloma venereum and granuloma inguinale.

Extraintestinal manifestations of ulcerative colitis following restorative proctocolectomy.

BACKGROUND: Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. OBJECTIVE: To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. METHODS: One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. RESULTS: Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. CONCLUSIONS: A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.

Reactive arthritis.

Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable infection at a distant site without traditional evidence of sepsis at the affected joint(s). Although several forms of disease could be described as "reactive", particularly acute rheumatic fever, post-meningococcal septicaemia arthritis and Lyme disease, in clinical practice the term is restricted to an acute spondyloarthritis, usually, but not exclusively, linked to acute genitourinary or gastrointestinal infection. A proportion of patients fulfil criteria for Reiter's Syndrome [1].