First-line therapy with rituximab may lower mortality risk in RA patients with lung conditions

November 13, 2016

Patients with rheumatoid arthritis who also have lung involvement often have increased mortality, but first-line therapy with rituximab may help them live longer when compared with the use of TNF inhibitors , according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington.

Rheumatoid (RA) is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

It's not common for RA to have pulmonary complications such as (ILD). However, when present, ILD leads to increased mortality rates. Some research suggests that treatment with tumor necrosis factor inhibitors (TNFi) may be linked to ILD development or worsening of ILD in RA patients. In 2005, the British Society for Rheumatology advised against using TNFi in patients with RA and ILD, but there was no data on whether rituximab (RTX) would have the same effect or may improve mortality in these patients. So researchers in the United Kingdom studied five-year mortality in RA-ILD patients who had started therapy with either RTX or TNFi.

"Treatment of the underlying arthritis among patients with RA-ILD can be complicated, as methotrexate is often contraindicated," said Kimme Hyrich, MD, PhD, FRCPC, Professor of Epidemiology and Honorary Consultant in Rheumatology at the Arthritis Research UK Centre for Epidemiology at the University of Manchester. "It's been unclear what the best choice of biologic therapy is for patients with RA-ILD and active arthritis given the relative contraindication for TNFi."

The study's aim was to analyze and compare among patients with RA-ILD who had started either rituximab or TNFi as their first biologic, including causes of . The researchers examined mortality data on participants in the British Society for Rheumatology Biologics Register for RA. They included patients with clinician-reported RA-ILD at baseline who started either TNFi or RTX as their first biologic therapy. They located the date and cause of death for each patient on study follow-up forms, as well as linkage with the UK National Death Register.

They calculated death rates per 1,000 person-years, and censoring occurred at death, at December 6, 2015, or five years after the patient's first registration, whichever came first. They also examined the frequency of ILD mentions on death certificates. Their next step was to generate Kaplan-Meier survival curves with risk comparisons made between RTX and TNFi cohorts using Cox regression and an ever-exposed model, adjusted for potential confounders. They determined the eligibility of confounders by clinically relevant justification or statistical significance (p<0.05), after adjusting for treatment effects.

The study included 353 eligible patients with RA-ILD. Of these, 310 were treated with TNFi and 43 were treated with RTX. All the patients in both groups were recruited before 2008. During the first five years of follow-up examination, there were 76 deaths in 804.9 person-years in the TNFi cohort of patients, and eight deaths in 156.7 person-years in the RTX cohort. Total death rates were 94.4 (74.4-118.1) and 51.0 (22.0-100.5) per 1,000 person-years respectively. ILD was recorded on 36.5 percent of the 74 available death certificates from the TNFi cohort and on all of the three certificates available in RTX cohort.

The researchers concluded that the unadjusted mortality risk in patients treated with RTX was numerically half of the risk found in patients treated with TNFi, although this was not statistically significant. Adjustment for baseline age, sex, disability, disease activity and disease duration had little affect on these estimates.

While patients with RA-ILD who received rituximab as their first-line therapy appeared to have a lower mortality risk than those who took TNFi first, the differences were not statistically significant, the researchers found. The registry data did not provide enough information on disease severity or ILD subtypes among these patients, so it was difficult to draw conclusions on the relative safety of these two therapies. In the future, larger and more detailed studies may help clarify safety issues for these therapies in this high-risk patient population.

"The main message is that the death rates among patients with RA-ILD who started RTX as their first biologic were lower compared to patients who started a TNFi. We did adjust our analysis for age, gender, disease duration and HAQ, which did differ between the two cohorts and are important risk factors themselves for mortality," said Dr. Hyrich. "However, because we did not have data on the severity of the lung disease itself, which is also an important risk factor for , it is unfortunately difficult to say with certainty that RTX is a better option for patients with RA-ILD in the absence of clinical trial data."

"Key to understanding this issue further will be a greater collection of data from patients with this history either separate to or within national registries. This is a rare condition, and without robust studies, guidance on the best choice of therapy to treat the underlying arthritis will remain limited to anecdotal evidence."

Explore further: Three gene sets could predict response to rheumatoid arthritis therapies

Related Stories

Three gene sets could predict response to rheumatoid arthritis therapies

November 13, 2016
Three gene expression signatures can help rheumatologists predict which patients are more likely to respond to tumor necrosis factor inhibitors (TNFi) or B-cell depletion therapies in patients with moderate to severe rheumatoid ...

Staying on dmards through surgery does not increase post-op infection risk

November 13, 2016
Rheumatoid arthritis patients who keep using their disease-modifying antirheumatic drugs prior to surgery do not face an increased risk of infection after their procedures, according to new research findings presented this ...

Tocilizumab treats rheumatoid arthritis after non-TNFi failure

March 30, 2016
(HealthDay)—For patients with rheumatoid arthritis (RA) and a first non-tumor necrosis factor inhibitor (TNFi) failure, treatment with tocilizumab seems more efficacious than abatacept or rituximab, according to a study ...

ACR: TNF inhibitors linked to reduced risk of ACS in RA

October 29, 2013
(HealthDay)—For patients with rheumatoid arthritis (RA), tumor necrosis factor inhibitor (TNFi) treatment correlates with reductions in the risk of acute coronary syndromes (ACS) and myocardial infarction (MI), according ...

Combination of NSAIDs and TNF-inhibitors shows benefit for ankylosing spondylitis

November 13, 2016
A combination of nonsteroidal anti-inflammatory drugs and TNF-inhibitors may help slow down spine damage in ankylosing spondylitis, according to new research findings presented this week at the American College of Rheumatology ...

TNF inhibitors may not modify polyarticular JIA disease process

June 19, 2015
(HealthDay)—For children with polyarticular juvenile idiopathic arthritis (JIA), discontinuing medications is challenging, with high relapse rates, especially after discontinuation of tumor necrosis factor inhibitor (TNFi) ...

Recommended for you

Fluid in the knee holds clues for why osteoarthritis is more common in females

June 26, 2017
Researchers have more evidence that males and females are different, this time in the fluid that helps protect the cartilage in their knee joints.

Biologics before triple therapy not cost effective for rheumatoid arthritis

May 29, 2017
Stepping up to biologic therapy when methotrexate monotherapy fails offers minimal incremental benefit over using a combination of drugs known as triple therapy, yet incurs large costs for treating rheumatoid arthritis (RA). ...

Drug for refractory psoriatic arthritis shows promise in clinical trial

May 24, 2017
In a pivotal phase-3 clinical trial led by a Stanford University School of Medicine investigator, patients with psoriatic arthritis for whom standard-of-care pharmaceutical treatments have provided no lasting relief experienced ...

Cross-species links identified for osteoarthritis

May 17, 2017
New research from the University of Liverpool, published today in the journal npj Systems Biology and Applications, has identified 'cell messages' that could help identify the early stages of osteoarthritis (OA).

Osteoarthritis could be prevented with good diet and exercise

May 12, 2017
Osteoarthritis can potentially be prevented with a good diet and regular exercise, a new expert review published in the Nature Reviews Rheumatology reports.

Rodents with trouble walking reveal potential treatment approach for most common joint disease

May 11, 2017
Maintaining the supply of a molecule that helps to nourish cartilage prevented osteoarthritis in animal models of the disease, according to a report published in Nature Communications online May 11.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.