Results from a retrospective analysis of contemporary data presented today at EULAR 2012, the Annual Congress of the European League Against Rheumatism, predict, based on estimates from a multivariate regression model, that the cumulative use of anti-tumour necrosis factor drugs (anti-TNFs) for one, two, or three years is associated with reduced risk of cardiovascular events by 24%, 42% and 56% in patients with rheumatoid arthritis (RA) respectively, compared to not using anti-TNF therapies (adjusting for background use of methotrexate or other disease modifying anti-rheumatic drugs [DMARDs]).

The model, based on 109,462 patients demonstrated that each additional six months of treatment with anti-TNFs significantly reduces the risk of cardiovascular events (myocardial infarction [MI], stroke/transient ischemic attack, unstable angina, or heart failure) (Hazard Ratio [HR]=0.87, p=0.005). Breaking this benefit down further, the same model shows that the risk of MI was also significantly reduced (HR=0.80, p=0.013).

Focusing on some subgroups of patients, each additional six months of anti-TNF therapy significantly reduced the risk of cardiovascular events in RA patients aged ≥50 years (HR =0.86, p=0.007) as well as in those without prior treatment with methotrexate (HR=0.85, p=0.022).

“RA and heart disease have a common origin and the systemic inflammation involved in RA is thought to also promote cardiovascular disease and even cardiovascular death. Studies have shown that within the first ten years of being diagnosed with RA, the risk of a heart attack almost doubles,” said Dr. Michael Nurmohamed, VU University Medical Centre & Jan van Breemen Research Institute, Reade, The Netherlands and lead study author. “As anti-TNFs are now the treatment of choice for patients who are unstable on methotrexate, the decreased cardiovascular risk observed in the study is an added bonus to an already successful class of drugs.”

The study using U.S. health plan claims identified 109,462 patients with ≥2 rheumatoid arthritis diagnoses and ≥1 filled prescription of anti-TNF therapy, methotrexate therapy, or other non-biologic DMARD. Patients were assessed from index fill date to first inpatient cardiovascular event diagnosis or to the end of health plan enrolment or to six months after discontinuation of their index drug, whichever came first. This included a total of 105,920 patient years of follow up, including 48,621 patient years of exposure to anti-TNFs, 35,480 patient years of exposure to methotrexate, and 52,994 patient years of exposure to other non-biologic DMARDs. A total of 1,743 patients (1.6%) had a cardiovascular event after their index prescription.

A study presented at EULAR 2012, the Annual Congress of the European League Against Rheumatism, reinforces current thinking that smoking negatively affects treatment response in rheumatoid arthritis (RA) patients treated with anti-tumour necrosis factor (anti-TNF) drugs.

This American study, the largest of its kind, followed 2,811 treatment naïve patients initiated onto anti-TNF therapy. Of the study group, 19% (n=521) were smokers and 81% (n=2,290) were non-smokers. Smokers had significantly higher scores on the Clinical Disease Activity Index (CDAI)* and DAS28** at six months than non-smokers. There was no significant difference in the odds of smokers versus non-smokers in achieving at least moderate EULAR*** response at six months and no difference in the change of mHAQ****.

Professor Ozlem Pala from the University of Miami Miller School of Medicine, USA and lead author of the study said: “There have been several studies which have investigated factors affecting response to anti-TNFs, but this is the first study to investigate response factors in such a large cohort of people. Being able to better predict response rates to treatment means that rheumatologists can discuss the findings with their patients who smoke and strongly encourage them to quit. This may also motivate them to develop successful strategies for smoking cessation in order to maximize effect of this expensive group of medications and potentially increase quality of life for these patients.”

Disease activity measures at baseline were similar for DAS28 (approximately 3.7, standard deviation [SD]: 1.6) for both groups but higher for CDAI (17.1, SD: 13.8 vs 15.5, SD: 12.9) and mHAQ (0.5, SD: 0.5 vs 0.4, SD: 0.4) in smokers and non-smokers, respectively.

Patients were taken from the Consortium of Rheumatology Researchers of North America (CORRONA) registry. Mean duration of follow-up per patient was 3.4 years (SD: 2.6). Patients enrolled in the study were followed for up to 10.2 years. Biologic naïve patients were followed for six months after initiation of an anti-TNF and outcomes of interest included DAS28, CDAI, mHAQ and EULAR response criteria after six months on therapy.

New data presented at the EULAR meeting (European League Against Rheumatism) show for the first time that MabThera (rituximab), a unique B cell targeted therapy, is able to significantly inhibit structural damage of joints caused by rheumatoid arthritis (RA). The study was conducted in patients who had an inadequate response to one or more TNF inhibitors and they received either MabThera plus methotrexate (MTX) or MTX alone. X-ray evidence at 56 weeks showed that the progression of bone erosions and progression of narrowing of joint spaces in patients in the MabThera group were reduced by more than 50 % compared to patients receiving MTX alone (erosion scores of 0.59 and 1.32 respectively; joint space narrowing scores of 0.41 and 0.99 respectively).

Damage to the structure of the joints ultimately causes destruction of the joints and contributes to joint deformity and loss of mobility. Patients’ ability to work and perform every day tasks such as getting dressed, walking and eating can be severely hampered.

Presenting the results, Professor Keystone, Rheumatology Department at the University of Toronto, Canada, said: “This is the first evidence demonstrating that MabThera can inhibit structural joint damage in patients with an inadequate response to one or more TNF inhibitors. Preventing structural damage is a critical outcome in treating rheumatoid arthritis. These X-ray data confirm MabThera as an effective and innovative therapy for patients with rheumatoid arthritis and highlight the value of targeting B cells.”

Repeat treatment courses
Additional new data presented at EULAR demonstrate that repeat courses of MabThera in RA patients, 6 to 12 months after the initial course, provide continued improvement of symptoms across all clinical measures. Each treatment course consists of two infusions of 1000mg given two weeks apart. The challenging goal of treatment in RA is remission and, following a second course of MabThera in patients with an inadequate response to one or more TNF inhibitors, the number of patients achieving remission doubled from 6 % following an initial course to 13 % following a second course. A similar trend was seen for those achieving the hard-to-reach goal of a 70 % improvement in symptoms (ACR70), with responses increasing from 12 % following an initial course to 21 % following a second course.

Patient perspectives
Importantly, data presented at EULAR show improvements in clinical scores are reflected in patient reported outcomes.

“While it is important to a physician to address a disease from a clinical perspective, what matters most to the patient is whether they are able to function normally and how well they feel. For example, the impact of fatigue is often underestimated, but this is something which really impacts patients’ lives. MabThera has demonstrated continuous improvements in physical and mental health aspects with repeated courses of therapy”, said Professor Tak, Director, Division of Clinical Immunology and Rheumatology at the Academic Medical Centre/University of Amsterdam, The Netherlands.