Rheumatology visit within 6 weeks of RA symptom onset increases chance for remission
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Visiting a rheumatologist within 6 weeks of symptom onset can benefit a patient with rheumatoid arthritis in achieving sustained, DMARD-free remission, but in slowing radiographic progression, according to data published in The Lancet Rheumatology.
“The European League Against Rheumatism (EULAR) recommendations for the management of early arthritis state that patients presenting with arthritis should be referred to, and seen by, a rheumatologist within 6 weeks after the onset of symptoms,” Ellis Niemantsverdriet, PhD, of Leiden University Medical Center, in the Netherlands, and colleagues wrote.
They added: “Although it is known that visiting a rheumatologist within 12 weeks of symptom onset is associated with less radiographic progression and a higher chance of achieving drug-free remission, there is currently no evidence that an initial visit within 6 weeks leads to improved long-term outcomes compared with an initial visit between 7 and 12 weeks.”
To analyze the impact of visiting a rheumatologist within 6 weeks of RA symptom onset on long-term outcomes, compared with a visit between 7 and 12 weeks of symptom onset, Niemantsverdriet and colleagues conducted an observational cohort study of consecutive patients from the Leiden Early Arthritis Clinic (EAC) and the French Etude et Suivi des Polyarthrites Indifferenciées Recentes (ESPOIR). The researchers examined 1,025 patients with RA from the EAC between Jan. 1, 1996, and Dec. 31, 2017, and 514 patients from the ESPOIR cohort between Nov. 1, 2002, and April 30, 2005.
Investigators grouped all patients based on time between symptom onset and first rheumatology visit. These categories included within 6 weeks, between 7 and 12 weeks and after 12 weeks. Primary outcomes included sustained DMARD-free remission and radiographic progression. The researchers used multivariable Cox regression, linear mixed models and meta-analyses in their ultimate findings.
According to the researchers, after 7 years of follow-up among patients from the EAC, 24% of the127 patients who visited within 6 weeks achieved sustained DMARD-free remission, compared with 20% of the 223 patients in the 7- to 12-week group, and 15% of the 675 patients who waited more than 12 weeks. Further, after 10 years of follow-up in the ESPOIR cohort, 27% of the 11 patients who visited within 6 weeks demonstrated sustained DMARD-free remission, compared with 11% of the 100 patients in the 7- to 12-week group, and 10% of the 403 patients who waited longer.
In the EAC multivariable analysis, those who visited a rheumatologist within 6 weeks achieved sustained DMARD-free remission more often than those seen between 7 and 12 weeks (HR = 1.59; 95% CI, 1.02-2.49), as well as those who waited longer (HR = 1.54; 95% CI, 1.04-2.29). Similar but non-significant effects were reported in the ESPOIR multivariable analysis.
The meta-analysis of both cohorts demonstrated that visits within 6 weeks of symptom onset was associated with a higher chance of achieving sustained DMARD-free remission than a time of 7 to 12 weeks (HR = 1.69; 95% CI, 1.10-2.57) or more than 12 weeks (HR = 1.67; 95% CI, 1.08-2.58).
Lastly, multivariable analyses in both cohorts demonstrated that patients who visited a rheumatologist within 6 weeks had similar radiographic progression to those seen between 7 and 12 weeks, as well as those seen after 12 weeks. The meta-analysis similarly showed that visiting within 6 weeks was not associated with less radiographic progression than a wait time of 7 to 12 weeks, but was linked with less radiographic progression than a wait time of more than 12 weeks.
“The decision about whether or not to try to implement the EULAR recommendation to see a rheumatologist within 6 weeks of symptom onset might depend on the long-term treatment aim,” Niemantsverdriet and colleagues wrote. “A beneficial effect was demonstrated for sustained DMARD-free remission, which is a proxy measure of resolution of disease chronicity. However, to minimize structural damage, a time to encounter of 6 weeks or less does not seem necessary.”
The researchers added, “Since clinically relevant joint destruction has become infrequent and sustained DMARD-free remission is increasingly achievable, achieving a time to encounter within 6 weeks, although challenging, might become of increasing importance.” – by Jason Laday
Disclosures: The researchers report funding from the European Research Council, the Dutch Arthritis Society, Merck Sharp & Dohme, INSERM, the French Society of Rheumatology, Pfizer, AbbVie, Eli Lilly and Sanofi.
Perspective
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David A. McLain, MD, FACP, FACR
In rheumatology practice, we know that it is important to see newly diagnosed rheumatoid arthritis as soon as possible. While we know this, the scheduling person at our office or clinic, however, may not or not be able to triage effectively. Joseph Grisanti, MD, medical director of Buffalo Rheumatology and Medicine, gives an early RA talk that shows a house on fire and that, with delay, the damage mounts.
A previous European study had shown the proportion of newly diagnosed RA patients seen by a rheumatologist within 12 weeks was low; however, a EULAR goal is for a newly diagnosed RA patient to be referred and seen by a rheumatologist within 6 weeks of symptom onset. The purpose of this observational cohort study was to see if there was any difference in groups seen within 6 weeks, 7 to 12 weeks, and greater than 12 weeks with regard to two outcomes.
The first outcome — which I would consider very difficult to achieve, and one that I feel I rarely see — was sustained DMARD-free remission. This was disease-free remission with absence of joint swelling after at least one year off DMARDs, biologics and prednisone. The second outcome was radiographic progression.
There was a British and a French side to this study with the British cohort followed for 21 years (1996-2017) and the French cohort for 4 years (2002-2005). The British cohort had a shorter wait time due to the existence of an early arthritis recognition clinic that had no wait list.
This study showed the time from the last swollen joint to DMARD-free sustained remission was 4.6 years and the median follow-up after discontinuing DMARDs was 5.6 years. DMARDs in this study were started within 2.4 weeks of being first seen by the rheumatologist. The differences in the DMARD-free sustained remission between the different groups (6 weeks, 7-12 weeks, and >12 weeks) was significant. The earlier the treatment, the better the remission rate.
The remission percentages for the British cohort were: 24% vs. 20% vs. 15%, for 6, 7-12, and 12 weeks, respectively, and 27% vs. 11% vs. 10% for the French cohort. Radiographic progression was not significantly different among the groups.
Like the European study noted above, the percentage of patients seen in the U.S. within 12 weeks is probably low. Some clinicians have adopted an early arthritis protocol to expedite visits with the help of their staff and in-office ancillary providers. Early RA recognition and treatment is a goal — as this paper shows — that we, as rheumatologists, need to continue to strive for.
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