European League Against Rheumatism, June 10-13, 2009
The 10th Annual Congress of the European League Against Rheumatology, which took place from June 10 to 13 in Copenhagen, Denmark, is an international platform which brings together physicians, surgeons, scientists, health professionals and patients. This year, a joint congress was held with colleagues from the Pediatric Rheumatology European Society. A wide variety of clinical innovations, translational research, and basic science was presented through over 300 oral and 1700 poster presentations, as well as symposia, state of the art lectures, and interactive sessions. This was the largest rheumatology-related event in Europe, with over 13,500 attendees representing over 100 countries.
Frank Heldmann, M.D., of the Rheumazentrum Ruhrgebiet in Herne, Germany, presented results from EASIC, an open-label follow-up study of the ASSERT trial, a randomized controlled study evaluating the anti-tumor necrosis factor therapy infliximab in patients with ankylosing spondylitis. A total of 103 patients (82.5 percent male, mean age of 43.5 years) who had participated in the ASSERT trial were recruited into the EASIC study. After five years of infliximab treatment, 61.8 percent experienced substantial clinical benefit and 27.6 percent achieved partial remission. A majority of patients had no arthritis and no enthesitis (78.4 and 84.9 percent, respectively). These patients experienced low disease activity, good functional status, and favorable spine motility, all of which had been substantially worse at baseline of the ASSERT trial. Significant improvements in levels of C-reactive protein and swollen joint count were also observed.
"The data show that infliximab therapy was associated with sustained efficacy and favorable attrition rates (less than 10 percent per year for any reason over five years)," Heldmann said in a statement. "Thus, our study confirms the role of infliximab as an effective and overall well tolerated treatment option in the management of patients with this chronic condition."
Edward Vital, M.D., of the University of Leeds in the United Kingdom, reported findings from a study which showed that patients with rheumatoid arthritis who failed initial treatment with the B-cell-depleting antibody therapy rituximab may benefit from a second course treatment after six months. According to a statement by Vital, "although rituximab can be effective in rheumatoid arthritis, around a third of patients fail to achieve an adequate response the first time they are treated." A total of 104 patients were included. Initial studies suggested that B cells were completely depleted from all patients following rituximab therapy, even in those who did not clinically respond. However, highly sensitive flow cytometry, a technique to measure very small numbers of B cells, subsequently revealed that 90 percent of patients who did not clinically respond to rituximab therapy had incomplete B cell depletion. A total of 25 patients, who did not respond to initial rituximab therapy were retreated after six months, at which point the B cells had not yet recovered to pretreatment baseline levels. After retreatment, 72 percent of patients exhibited a clinical response, and 48 percent achieved complete B cell depletion by highly sensitive flow cytometry. These patients also experienced a significant improvement in disease activity score.
In a statement, Vital said, "our study has shown that retreating patients at a specific stage can enhance clinical responses to a level equal to those who fully respond to the rituximab course at first administration. This provides hope for patients who are classified as non-responders and would normally have limited other treatment options. The next question is whether patients who have predictors of poor response could be treated more intensively from the outset, for example with a different dose of rituximab."
Some of the study authors reported financial relationships with Roche.
Marianne Wallenius, Ph.D., of the Norwegian University of Science and Technology in Trondheim, presented results from a retrospective study which demonstrated that nulliparous women (those who have not given birth) are diagnosed with some types of chronic arthritis an average of 5.2 years earlier than parous women (those who have given birth). The study included 557 women (aged 18 to 45 years) diagnosed with either ankylosing spondylitis, psoriatic arthritis, or rheumatoid arthritis; of these women, 163 were nulliparous and 394 were parous. The mean age at the time of diagnosis was significantly older for nulliparous compared with parous women (31.2 versus 26 years; relative risk, 1.83). Although nulliparous women had a significantly higher education level, when adjusted for education level and smoking status (both of which were similar among the two groups), a significant difference in the age at diagnosis was still observed (relative risk, 1.23).
In a statement, Wallenius concluded, "our study indicates that the processes of pregnancy and childbearing could delay the onset of arthritic conditions," adding, "continued examination of the complex interactions between the female reproductive processes and the epidemiology of rheumatoid arthritis could yield further interesting insights."
Miguel Sousa, M.D., of the Instituto Portugues de Rheumatology in Lisbon, Portugal, presented a study which showed that a supervised exercise program was beneficial for patients with rheumatoid arthritis, not only improving functional status and physical function, but also reducing the need for more medication. In this observational longitudinal study, eight rheumatoid arthritis patients (mean age of 59 years) with stable disease who were physically inactive were followed over three months. The three-month exercise program consisted of 50 to 60 minutes of moderate aerobic and strengthening exercises conducted three times weekly. Functional status, measured as the ability of the patient to perform daily tasks such as dressing, eating and walking, was significantly improved by 33 percent. Similarly, significant improvements in physical function were also observed, including a 55 percent improvement in a sit and stand test, a 19 percent improvement in the timed walk test, and a 10 and 15 percent improvement in the right-hand and left-hand grip test, respectively. A majority of patients (62 percent) reported a reduced need for daily corticosteroid therapy, and 32 percent reported no longer taking concurrent non-steroidal anti-inflammatory drug treatment after completion of the exercise program. Patients also experienced a 40 percent improvement in the Depression Anxiety Stress Scales, a self-reported measure of negative emotional status.
"When joints are stiff and painful, proactively taking exercise might seem undesirable for people with rheumatoid arthritis," Sousa acknowledged in a statement. "However, our study has demonstrated that regular and supervised moderate aerobic workouts and strengthening exercises may be extremely beneficial for both a patient's physical and mental health." Sousa further noted that, "the challenge for physicians is to provide suitable motivation and reassurance to their rheumatoid arthritis patients in order that they initiate and stick with such a program."
Shunichi Shiozawa, M.D., of the Kobe University Graduate School of Medicine and University Hospital in Japan, reported research findings which suggested a link between the circadian rhythm genetic pathway and rheumatoid arthritis. In a statement, Shiozawa said, "the identification of this curious pathway may help to explain the 24-hour symptom cycle seen by many patients who experience worsening of joint pain and stiffness in the mornings." In 200 patients with rheumatoid arthritis, sleep was found to be significantly disturbed in approximately 61 percent of the patients, indicated by a Pittsburg Sleep Quality Index (PSQI) score over five; the global PSQI score was 8.55 ±4.69. The PSQI scores correlated with arthritic disease activity, assessed by C-reactive protein levels, swollen joint count, and other markers of inflammation. Shiozawa further reported that mice in whom experimental arthritis was induced exhibited a two-fold increase in activation of a promoter for a gene which codes for the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha. This increase was attributed to the activity of the circadian regulatory gene CRY.
"Our study has shown that arthritis interferes with the genetics behind an individual's circadian rhythm and, specifically, that certain body clock genes may play a part in the activation of TNF-alpha," Shiozawa concluded.
Several pediatric-related studies were also presented in conjunction with the Pediatric Rheumatology European Society joint congress. One study reported promising efficacy results for the interleukin-1β-inhibiting monoclonal antibody, canakinumab, in children with juvenile idiopathic arthritis, while a separate study showed a different interleukin-1 antagonist, anakinra, produced a good clinical response in patients with newly diagnosed systemic onset juvenile idiopathic arthritis. Three studies individually demonstrated the anti-tumor necrosis factor therapy, etanercept, was safe and effective in young children (under 4 years of age) with juvenile idiopathic arthritis.