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Regularly consuming tea may lower the risk of developing rheumatoid arthritis (RA), especially for current smokers and in anti-citrullinated autoantibody (ACPA)-positive RA, according to a study published in 

“In recent years, diet has gained attention for its potential immunomodulatory effects. After water, tea is the most popular drink in the world [and] all kinds of tea are rich in polyphenols, which are antioxidants that may reduce the risk of inflammatory diseases such as RA,” investigators explained. “However, studies on tea consumption and the risk of developing RA have thus far shown inconclusive results.”

Data from the population-based, case-control study, EIRA, was collected for 2237 patients with RA diagnosed between 2005 and 2018 and 4661 controls that were matched for age, sex, and residential area. Participation rate was 90% for the RA cohort and 69% for the controls.

Tea consumption was classified as no (0 cups/day), irregular (< 1 cup/day), regular (1-2 cups/day), and high (≥ 2 cups/day). Herbal tea was classified as no (0 cups/day), irregular (< 1 cup/day), and regular (≥1 cup/day).

Results were adjusted for lifestyle factors, such as smoking habits, alcohol intake, and coffee consumption, as well as body mass index, and educational level.

The control group was more likely to be high consumers of tea when compared with the RA cohort (22.1% vs 19.7%, respectively). In the RA group, 57.3% drank tea and 19.7% were classified into the high tea consumption category. A total of 58.4% of participants in the control group drank tea and 22.1% were high tea consumers. Additionally, those who were tea consumers were less likely to smoke or drink coffee and had a lower alcohol intake. Smoking was more prevalent in the RA cohort (22.5% vs 13.8%).

While tea consumption and risk of RA was not linear, there was a reduction in odds for those who consumed 1 or more cups per day. High consumption was associated with a 22% lower risk when compared with irregular consumers. However, after adjusting for covariates, results were no longer statistically significant. Participants who regularly drank herbal tea had a borderline statistically reduction in risk of developing RA when compared with irregular consumers (adjOR = 0.77, 95% CI 0.58–1.02).

The odds of developing ACPA-positive RA were significantly lower in the high tea consumer group when compared with irregular tea consumers (adjOR = 0.76, 95% CI 0.62–0.94). Lowest odds ratio was seen in current smokers (adjOR = 0.60, 95% CI 0.38–0.95).

The study was strengthened by the participation rates and study design. However, tea consumption data was missing for a large percentage of participants, which investigators chose to classify in the no tea consumption group. This notion was backed up by the fact that proportion of tea drinkers was in line with Swedish statistics on tea sales. Irregular tea consumption was used as a reference. Recall bias may have altered the results of the study; however, it was not believed to have impacted the amount of missing data as percentages were similar in both the RA cohort and the control group.

“This study showed an inverse association with the risk of RA among high tea consumers compared to irregular consumers among smokers and in the ACPA-positive subset of RA,” investigators concluded. “We could not draw any conclusion about no tea consumption and the risk of RA, due to the possibility of bias.”

Westerlind H, Palmqvist I, Saevarsdottir S, Alfredsson L, Klareskog L, Di Giuseppe D. Is tea consumption associated with reduction of risk of rheumatoid arthritis? A Swedish case-control study. 

. 2021;23(1):209. Published 2021 Aug 7. doi:10.1186/s13075-021-02583-y

Articles

While the antioxidants in tea may reduce the risk of developing inflammatory diseases, such as rheumatoid arthritis, previous studies have shown inconclusive results. 

Drinking Tea May Protect Patients From Developing Rheumatoid Arthritis 

Rheumatology Network's Top 5: September 17, 2021

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending September 17, 2021.


Single data point serum urate (sUA) measurements were proven undependable in classifying hyperuricemia, defined as elevated uric acid levels in the blood, due to spontaneous variation, according to a study published in 

 However, results showed that patients with an sUA of < 6.0 mg/dL were less likely to have future hyperuricemic measurements.

“In addition to its well-described role in the pathogenesis of gout, hyperuricemia (sUA > 6.8 mg/dL) is associated with vascular, cardiac and renal disease. This hyperuricemic threshold, or similar ones based on sUA distributions in populations of men and women, are commonly used in epidemiological and clinical research,” investigators stated. “However, the reliability of a single sUA measurement in defining hyperuricemia is unclear.”

Information was taken from the cross-over clinical trial Serum Urate Reduction to Prevent Hypertension (SURPHER) study to determine the efficacy of single data point sUA measurements in young adults without the presence of gout. Patients included in the study were between the ages of 18 and 40 years, had systolic blood pressure (SBP) ≥ 120 and < 160 mmHg or diastolic blood pressure (DBP) ≥ 80 and < 100 mmHg, and a sUA of ≥5.0 mg/dL for men or ≥ 4.0 mg/dL for women. The sUA levels were measured at baseline and then in 2-to-4-week intervals. After the first interval, patients either received allopurinol 300 mg daily or placebo. sUA was then measured again after a washout period, which ensured the dissipation of the effects of allopurinol. sUA measurements were ideally taken between 7 and 11 AM and patients were instructed to fast the day prior.

Investigators analyzed sUA levels at screening, pre-intervention, pre-placebo, and post-placebo. Mean coefficient of variation for sUA was compared across all cohorts and analyzed to detect any differences. Conversion rates from normouricemia (≤6.8 mg/dL) to hyperuricemia (> 6.8 mg/dL) and from hyperuricemia to normouricemia were calculated and compared across subgroups.

In total, 85 participants completed all 4 sUA measurements. The mean age was 27.8 years, 39% were female, and 41% were African American. Unfortunately, of the 76% of patients in which time of day data was available, 84% were measured outside of the 4-hour timeframe.

Variation in sUA was 8.5% ± 4.9% (1 to 23%) and there was no significant difference between men (8.5%) and women (8.6%) (p = 0.88) or between those normouricemic (8.6%) and hyperuricemic (8.0%) (p = 0.68) at baseline. For patients in the normouricemic group, 21% were hyperuricemic at 1 or more follow-up visits. Initial sUA levels of < 6.0 (n = 54) were significantly less likely to have hyperuricemia when compared with participants with sUA levels between 6.0-6.8 (n = 18) (7% vs 39%, respectively). In patients with hyperuricemia at baseline, 46% were normouricemic at 1 or more follow-up.

While the small sample size was limiting, it may inspire larger studies in the future. The initial screening of sUA was not standardized to a certain time of day and several measurements were taken outside of the 2-to-4-week intervals, which may have impacted results, as concentration levels are higher in the morning. As participants were younger, it could limit generalizability to older patients. Allopurinol and placebo dosing may have affected results as well, but investigators minimized that chance by confirming dissipation of allopurinol with a 2-sample t-test. Finally, the SURPHER criteria required initial sUA of ≥5.0 mg/dL for men and ≥ 4.0 mg/dL for women, thus excluding patients with lower sUA levels.

“Our data is consistent with previous studies which have found significant variation in sUA levels over time, even when controlling for commonly identified influencers of sUA levels,” investigators concluded. “Future studies could examine the reliability of sUA checks in those with gout, as well as those on urate-lowering therapy (ULT), to determine whether a treat-to-target approach for gout flare suppression may be subject to these same fluctuations in sUA levels.”

Shaffer A, Rahn E, Saag K, Mudano A, Gaffo A. Variation in serum urate levels in the absence of gout and urate lowering therapy. 

. 2021;5(1):32. Published 2021 Sep 8. doi:10.1186/s41927-021-00202-6

Hyperuricemia is associated with vascular, cardiac, and renal disease, as well as gout. However, the reliability of a single measurement in defining hyperuricemia is unclear.

Single Serum Urate Measurements Deemed Unreliable for Identifying Hyperuricemia 

Pregnant women with rheumatic disease who developed COVID-19 had promising outcomes, offering cautious optimism for this patient population, according to a study published in 

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“Rheumatic diseases commonly occur in reproductive-aged women. The impact of pregnancy on the underlying rheumatic disease, the rheumatic disease impact on pregnancy, and the limitations in the use of anti-rheumatic medications can make disease management challenging,” investigators explained. “With the global outbreak of the novel COVID-19, an additional level of complexity has been added for women with rheumatic diseases who wish to become pregnant.”

Health care providers have been collecting data from patients with rheumatic disease diagnosed with COVID-19 since March 24, 2020. Information is then entered into the COVID-19 Global Rheumatology Alliance (C19-GRA) provider REDCap survey. Data includes patient age, sex, race and ethnicity, country, city, and clinic. It also provides details of disease activity, comorbidities, current medication usage, and COVID-19-related information, such as symptoms, treatments, outcomes, and diagnosis date.

This study analyzes pregnant patients between March 24, 2020 and January 14, 2021 and includes 2 follow-up REDCap surveys performed on July 1, 2020 and January 15, 2021. Additional details requested were gravida, gestational age at COVID-19 diagnosis, medication usage through COVID-19 illness, and obstetric outcomes. Data was then compared with non-pregnant women from the C19-GRA registry.

A total of 39 patients were included in this study, with a median age of 33 years. The most common race/ethnicity was White (33%), followed by Latin American/Hispanic (23%), Arab or Middle East (23%), South or East Asian (15%), and Black (5%). While comorbidities were infrequent, they included pre-pregnancy hypertension (n = 3), morbid obesity (n = 2), obesity (n = 1), pregestational diabetes mellitus (n = 1), and psoriasis (n = 1).

Mean gestation at COVID-19 diagnosis was 23.3 weeks, with 3 developing COVID-19 in the first trimester, 13 in the second trimester, and 6 in the third trimester. Rheumatic diseases included rheumatoid arthritis (RA) (n = 9), systemic lupus erythematosus (SLE) (n = 9), psoriatic/other inflammatory arthritis (PsA) (n = 8), and anti-phospholipid antibody syndrome (n = 6). Most patients had minimal or low disease activity (n = 18) or were in remission (n = 13).

Roughly a quarter (n = 10/39) were hospitalized due to COVID-19 illness, but only 2 required supplemental oxygen. No women delivered due to COVID-19 infection and no patients died. The most common symptoms included cough (n = 24), fever (n = 21), headache (n = 12), anosmia (n = 11), shortness of breath (n = 11), and myalgia (n = 11), although 3 patients were asymptomatic. Of the 39 patients, 82% (n = 32) did not require any specific medication treatment during their illness.

The small number of patients and incomplete data limits the study. Additionally, as information was submitted voluntarily, there is a chance that selection bias regarding complex and active disease as well as more severe COVID-19 cases may have impacted results. Lastly, favorable outcomes may have had more to do with the fact that patients were young, had few co-morbidities, and were on lower glucocorticoid doses.

“Pregnancy and COVID-19 outcomes in pregnant patients with systemic rheumatic disease were relatively benign in this patient series,” investigators concluded. “However, data on all pregnancy outcomes and whether there were any cases of vertical transmission to infants is not available. Additional cases with greater granularity of data regarding pregnancy and fetal outcomes in the rheumatic disease population will greatly enhance our knowledge in this area.”

Bermas BL, Gianfrancesco M, Tanner HL, et al. COVID-19 in women with rheumatic disease who are pregnant: Data from the COVID-19 Global Rheumatology Alliance [published online ahead of print, 2021 Sep 1]. 

. 2021;jrheum.210480. doi:10.3899/jrheum.210480

COVID-19 has added an additional level of complexity for patients with rheumatic disease who wish to become pregnant. 

Favorable COVID-19 Outcomes in Pregnant Women With Rheumatic Disease 

Golimumab (GLM) was shown to be a safe and effective long-term treatment for patients with psoriatic arthritis, according to a study published in 

 Factors such as gender, smoking habits, BMI, comorbidities, and lines of treatment did not significantly impact results.

“Treatment recommendations underline the relevance of the burden of skin psoriasis (PsO) in patients affected by PsA and skin manifestations need to be a relevant part of the decision-making process for PsA therapeutic approach,” investigators explained. “However, the effectiveness evaluation of GLM in a real-life setting is a crucial issue, in particular for skin manifestation.”

In this retrospective, observational study, data from patients with moderate-to-severe psoriatic arthritis being treated with GLM between August 2011 and December 2020 were collected and compared at baseline and 6 (T6), 12 (T12), 24 (T24), 36, (T36), and 48 (T48) months. The primary endpoints were to determine the safety of a 4-year follow-up of patients treated with GLM, as well as the efficacy on both joint and skin manifestations in this patient population. Eligible patients were aged > 18 years, had a clinical diagnosis of PsA, concomitant and PsO according to the Psoriasis Area Severity Index (PASI), peripheral arthritis in at least 1 active joint, and were receiving GLM treatment. Previous use of biologic disease-modifying antirheumatic drugs (bDMARDs), concurrent conventional synthetic DMARDs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroid therapy were recorded at both baseline and follow-ups.

Safety was determined by analyzing the number of adverse events and retention rate was estimated at each follow-up. Patients were evaluated using the Bath Ankylosing Spondylitis disease activity index (BASDAI), a Disease Activity in Psoriatic Arthritis (DAPSA) score, and a Ankylosing Spondylitis Disease Activity Score-C-reactive protein (ASDAS-CRP) score. The presence of dactylitis, enthesitis, and a tender and swollen joint count were collected. PASI was assessed by a dermatologist.

Of 105 patients with moderate-to-severe PsA, 80% exhibited psoriasis (PsO), 78% had enthesitis, 63,8% had peripheral arthritis, and 35.5% presented axial arthritis at baseline. The most common comorbidities were cardiovascular disease (33.14%) and metabolic syndrome (MetS) (19%). A total of 31.4% of patients were smokers, 37.1% were overweight, and 19% were classified as obese.

ASDAS-CRP and BASDAI (p < 0.0001) levels were reduced at each of the follow-up visits. Dactylitis was reduced from 8.6% at T6 to 0% at T48. Enthesitis decreased from 49.5% at T6 to 1.9% at T48. PASI (p < 0.01) significantly improved throughout the study.


Decreased CRP levels were seen at all subsequent follow-ups (T6, T12, T24 [p < 0.0001]; T36 [p = 0.0009]; and T48 [p = 0.0007]). GH and pain were reduced, (p < 0.0001), and disability improved (T6 [p < 0.0001], T12 [p < 0.0001], T24 [p < 0.0001], T36 [p = 0.0005], and T48 [p = 0.0002]). DAPSA ( p < 0.0001) was seen in 62.1% at T6, 63.6% at T12, 55.4% at T24, 61.5% at T36, and 61.5% at T48. Further, remission was achieved in 12.6% at T6, 20,8% at T12, 26.2% at T24, 36.8% at T36, and 36.8% at T48.

Interestingly, thyroid disease lowered the likelihood of treatment persistence (p = 0.030), although there was no correlation between MetS and therapy persistence (p = 0.238). There was no significant difference between patients who had taken other biologicals and those who were biological naïve (p = 0.208).

The retention rate was 82.8% at 6 months, 73.4% at 12 months, 62% at 24 months, and 54.4% at 38 months. Gender, BMI, smoking status, and comorbidities did not impact results. Reasons for discontinuation were primary inefficacy (n = 13), secondary inefficacy (n = 21), lost at follow-up (n = 5), mild infection (n = 5), and surgery unrelated to GLM (n = 1).

Limitations included the retrospective nature of the study, low cutaneous disease activity at baseline, the lack of imaging in follow-up visits, and the small sample size.

“Treatment efficacy was supported by a good drug persistence of GLM regardless of the presence of comorbidities and patients’ characteristics,” investigators concluded. “Our results were consistent with no differences in terms of clinical response and efficacy between males and females, smokers and no-smokers, obese and normal-weight patients, and lines of treatment, confirming GLM efficacy and safety in a long-term real-life setting.”

Chimenti MS, Conigliaro P, Caso F, et al. Long-term effectiveness and drug survival of golimumab in patients affected by psoriatic arthritis with cutaneous involvement [published online ahead of print, 2021 Aug 19]. 

. 2021;10.1007/s10067-021-05874-6. doi:10.1007/s10067-021-05874-6

The efficacy evaluation of golimumab is crucial for patients with psoriatic arthritis, particularly for treating skin manifestations and psoriasis symptoms. 

Long-Term Golimumab Treatment in Patients With Psoriatic Arthritis 

Many patients with rheumatoid arthritis (RA) had 2 ore more unhealthy lifestyle factors, thus implying a complex relationship between these factors and disease impact, according to a study published in 

“It is important to remember that lifestyle habits are modifiable risk factors,” stated investigators. “However, changing them is known to be a challenge for everyone, potentially affecting quality of life. The higher the number of unhealthy lifestyle habits, the bigger the challenge, according to people living with RA, who must also deal with the symptoms of living with a chronic inflammatory disease.”

In this cross-sectional study, participants from 2 Scandinavian countries, Denmark (n = 289) and Sweden (n = 955), were analyzed to determine the impact unhealthy lifestyle factors had on disease impact. Investigators focused on smoking, body mass index (BMI), physical activity, and alcohol intake and were classified as healthy vs unhealthy. Swedish participant data was taken from the Better Anti-Rheumatic Pharmacotherapy (BARFOT) and Danish data was retrieved from the Danish Hospital for Rheumatic Diseases. Both countries treat patients with RA based on the European Alliance of Associations for Rheumatology (EULAR).

Healthy physical activity was defined as at least 150 minutes of exercise per week. Alcohol intake was analyzed based on being either above or below each country’s recommended limit. Smoking habits were based on tobacco use or the absence of it. Disease activity was determined by the Health Assessment Questionnaire (HAQ), EurolQol-5 Dimensions (EQ-5D), the visual analogue scale (VAS) in Denmark, and the numeric rating scale (NRS) in Sweden.

In the Danish cohort, 95% of participants self-reported at least 1 unhealthy lifestyle factor, and 66% had 2 or more, compared with 82% and 47%, respectively, in Swedish participants. The most common factors were a lack of physical activity and being overweight or obese. In the Danish group, 63% were overweight or obese and 84% did not achieve the recommended physical activity, compared with 54% and 52%, respectively, in the Swedish cohort.

In both cohorts, the women were both significantly younger and reported worse fatigue and function compared with the men. Similarly, men in both cohorts were linked to an increased risk of exhibiting 2 or more unhealthy lifestyle factors (Denmark: OR 1.86, 95% CI 1.21–2.85; and Sweden: OR 1.42, 95% CI 1.07–1.89). In the Danish cohort, cardiovascular disease (CVD) (OR 1.90, 95% CI 1.28–2.82) and disease duration (OR 0.97, 95% CI 0.95–0.99) were associated with 2 or more unhealthy lifestyle choices. In the Swedish cohort, participants with 2 or more unhealthy lifestyle factors were linked to worse HRQoL (EQ5D-3L, p = 0.001) and worse physical function (p < 0.001) when compared with those with no unhealthy factors.

Well-defined groups, with a broad perspective on lifestyle factors, strengthened the study. However, the small sample size both limited the number of patients that could be classified as having none or all 4 habits and may have affected generalizability. However, patients with rheumatoid arthritis are historically more likely to be overweight or obese and less physically active when compared with the general population. Additionally, while BMI was the factor that classified patients as healthy or unhealthy, rheumatoid arthritis increases the likelihood of cachexia, which could lead to misclassification of some patients. Lastly, the self-reported nature of the data may have led to some inaccuracy.

“In addition to the burden of living with long-standing disease, a large proportion of the patients in our two RA cohorts reported more than one unhealthy, but modifiable lifestyle factor of importance for the risk for CVD,” investigators concluded. “Our study supports that health professionals in rheumatology need to support healthy lifestyle changes in patients with RA and with a special focus on men and physical activity and dietary interventions.”

Karstensen JK, Primdahl J, Andersson MLE, Christensen JR, Bremander A. Lifestyle factors in patients with rheumatoid arthritis-a cross-sectional study on two Scandinavian cohorts [published online ahead of print, 2021 Sep 9]. 

. 2021;10.1007/s10067-021-05905-2. doi:10.1007/s10067-021-05905-2

While lifestyle habits are modifiable risk factors, changing them can be especially challenging for patients with rheumatoid arthritis, who must also deal with chronic inflammatory disease. 

The Relationship Between Unhealthy Lifestyle Factors and Rheumatoid Arthritis 

More than half of patients with psoriatic arthritis (PsA) had a diagnostic delay of more than 2 years and data showed no significant improvement in diagnostic time between 2000 and 2017, according to a study published in 

Those most likely to have diagnostic delay were patients who developed PsA at a younger age, had higher body mass index (BMI), or enthesitis. Patients with sebopsoriasis were among the least likely to experience delay.

“There is increasing evidence that early diagnosis and treatment of PsA leads to improved long-term outcomes for patients in terms of disease severity and radiographic damage. Delays in diagnosis of even 6–12 months have been shown to be associated with joint damage and poor functional outcomes,” investigators stated. “Despite this, the majority of patients have significant delays in the diagnosis of PsA; up to 40% have not been previously identified in screening studies.”

This retrospective, population-based study utilized medical records from Olmsted County, Minnesota to analyze diagnostic delay in patients 18 years or older with PsA  between January 1, 2000, and December 31, 2017. PsA was determined using the ClASification of Psoriatic Arthritis (CASPAR) criteria. Symptom onset was defined by the first PsA-related musculoskeletal symptom, such as those related to joints or enthesis.



Demographics, radiographic features, clinical characteristics, and laboratory data were collected. Psoriasis was confirmed by medical records and severity was determined using factors including body surface area involvement and distribution of involved areas.

The primary outcome was the delay in symptom onset to diagnosis of more than 2 years. The secondary outcomes analyzed delays in diagnosis at the 6-month and 1-year marks.

Investigators analyzed 162 incident PsA cases that had a clinician diagnosis. The mean age at symptom onset was 41.5 (12.6) years and 46% of patients were female. All patients met CASPAR criteria and displayed distal interphalangeal erosions on radiographs. The median time to diagnosis was 2.5 years (IQR 0.5–7.3). After symptom onset, only 23% (n = 38) patients were diagnosed with PsA, 35% (n = 56) by 1 year, and 45% (n = 73) by 2 years. Investigators did not observe any trends in symptom onset to diagnosis over the course of the 17 years (P = 0.84).

While there were no significant differences between patients with and without diagnostic delay regarding sex, psoriasis severity, family history, education level, smoking status, or alcohol intake, a few trends emerged. It appeared that younger patients (OR per 10-year decrease = 1.34, 95% CI 1.04–1.74), those with a higher BMI (OR per 10 kg/m2 increase = 1.89, 95% CI 1.15–3.10), and those with enthesitis (OR 2.20, 95% CI 1.08–4.46) were linked to a greater chance of diagnostic delay of more than 2 years. Conversely, those with sebopsoriasis had a lower likelihood of delay (OR 0.19, 95% CI 0.04–0.97).

Near-complete ascertainment of PsA cases using CASPAR criteria strengthened the study. However, its retrospective nature brings forth limitations regarding the completeness of medical record documentation. As only symptoms that were recorded could be analyzed, it is possible that the exactness of symptom onset is inaccurate. Additionally, as the population was 90% White, the results may not be generalizable to other racial or ethnic populations.

“More than half of the PsA patients in our study had a diagnostic delay of > 2 years,” investigators concluded. “A better understanding of factors associated with diagnostic delay may help in earlier diagnosis and management to improve outcomes in high-risk PsA patients. As not all patients have severe or progressive disease, identifying high-risk patient subgroups will be important to stratify those who will benefit from early, aggressive treatment.”

Karmacharya P, Wright K, Achenbach SJ, et al. Diagnostic Delay in Psoriatic Arthritis: A Population-based Study. 

. 2021;48(9):1410-1416. doi:10.3899/jrheum.201199

Early diagnosis and treatment of psoriatic arthritis leads to better long-term outcomes. Despite this, most patients have significant diagnostic delays. 

Diagnostic Delay Seen in Most Patients With Psoriatic Arthritis 

Ingrid Torjesen is a UK-based freelance health journalist with more than 30 years of experience in health and medical communications. She works for numerous publications including Rheumatology Network, the BMJ and the Economist’s Intelligence Unit. Before her freelance career, her staff jobs included news editor of both Pulse and GP (the two leading UK weekly titles for primary care doctors), and opinion and features editor of the Health Service Journal (the UK’s leading health policy title). She also spent a few years working in Australia, including on Australian Doctor.

Methotrexate has an established efficacy and safety profile

Safety concerns about JAK inhibitors highlighted by the Food and Drug Administration in a black box warning

The latest efficacy data on JAK inhibitors was not considered when formulating the latest guidelines

JAK inhibitors are not licensed for use in this way

Combination of methotrexate plus a non–TNF inhibitor

Combination of methotrexate plus tsDMARDs

Effective treatment for patients with moderate-to-severe rheumatoid arthritis can control symptoms quickly and slow disease progression. How should such patients be managed? Test your knowledge with this quiz.

Rheumatoid Arthritis Quiz: Initiating Therapy in Patients With Moderate-to-Severe Rheumatoid Arthritis

While perceived risk of COVID-19 varied among patients with rheumatoid arthritis (RA), respondents who perceived a higher risk where more likely to adhere to strict shielding, according to a study published in 

“The coronavirus disease 2019 (COVID-19) pandemic has strongly impacted the lives of patients living with RA because of concerns and uncertainties regarding their risk for infection and severe outcomes, which have contributed to anxiety, depression, and reduced well-being,” investigators stated.

Participants with RA were surveyed between July 16 and November 8, 2020. Included in the 25-question survey were questions about medication use, COVID-19 diagnosis, perception of COVID-19 risk, and any shielding practices. Investigators further analyzed any association between disease-specific factors or demographics with the perception of risk and shielding measures. Potential participants were selected from the Mass General Brigham (MGB) Research Patient Data Registry (RPDR). Eligible patients had a self-reported diagnosis of RA, a code for inflammatory arthritis (M05-M14), and were being treated with at least 1 disease-modifying antirheumatic drug (DMARD), such as abatacept, interleukin (IL)-6 inhibitors, janus kinase inhibitors (JAKis), methotrexate, or tumor necrosis factor inhibitors (TNFis). Demographics, such as age, sex, and race, as well as disease activity, were collected.

Risk perception was determined using a 5-level scale, with answers ranging from strongly agree to strongly disagree, in regard to the statement: “I am worried that my rheumatic condition or its treatment puts me at a higher risk for COVID-19 or severe complications if I become infected.”

A total of 494 patients with RA were included in the study. The majority of participants were white (91%), female (85%), and nonsmokers (52%). Mean disease activity was 74.6 (19.9). Of these participants, 40% strongly agreed that their rheumatic disease put them at a higher risk for developing COVID-19, 34% (n = 169) agreed, and 26% (n = 130) were either uncertain or disagreed. Younger patients, (odds ratio [OR]: 0.98; 95% confidence interval [CI]:0.96-0.99; P = 0.007), those with a comorbidity (OR: 1.60; 95% CI: 1.09-2.36), and those with recent DMARD use (OR: 1.7;5 95% CI: 1.14-2.68; P = 0.046) were more likely to have a higher perceived risk.

Shielding measures included social distancing, glove or mask use, and quarantine. Most patients were using at least 1 shielding practice at the time of the survey, with 74% quarantining, 96% using masks and/or gloves, and 98% social distancing. Patients with a higher perceived risk were 4 times more likely to utilize all 3 methods.

Free-text responses revealed that the mental health was a common concern for patients with RA, including anxiety, stress, depression, and feelings of uncertainty and fear.

The study was limited as it was originally conduced in mid-2020 and patients’ perceptions of risk may have changed since that time. The demographics (white, female) may limit generalizability; however, the registry included a variety of care facilities with a spectrum of disease severity and DMARDs. It is also important to consider both recall bias and social desirability bias, although patients were told that their answers would not be shared with their rheumatologist.

“The factors associated with COVID-19 risk perception in participants with RA may differ from risk factors reported in observational studies,” investigators concluded. “These findings highlight the importance of patient education campaigns. Additional studies are needed to clarify factors driving risk perception and shielding practices and the impact of these risks and practices on mental health.”

Cook C, Cox H, Fu X, et al. Perceived Risk and Associated Shielding Behaviors in Patients With Rheumatoid Arthritis During the Coronavirus 2019 Pandemic [published online ahead of print, 2021 Sep 8]. 

. 2021;10.1002/acr2.11340. doi:10.1002/acr2.11340

“The COVID-19 pandemic has strongly impacted the lives of patients living with rheumatoid arthritis which has contributed to anxiety, depression, and reduced well-being.” 

Perceived Risk of COVID-19 Infection in Patients With Rheumatoid Arthritis

Rheumatology Network's Top 5: September 10, 2021

Take 5 minutes to catch up on Rheumatology Network's highlights from the week ending September 10, 2021.


Patients with either diagnosed or suspected obstructive sleep apnea (OSA) have a higher likelihood of developing gout, according to a study published in 

 Further, patients with gout more frequently reported insomnia, restless legs syndrome, and worry about their sleep.

“There is likely to be a bidirectional relationship between sleep and gout, as gout flares may be influenced by circadian rhythms, and sleep quality is likely to be influenced by gout flares,” investigators explained. “Given the morbidity associated with sleep problems, we should be vigilant regarding sleep health in our patients with gout.”

In this cross-sectional online survey of 2044 Australian adults, investigators assessed self-reported and doctor diagnosed OSA, as well as patient-reported sleep outcomes, to determine the prevalence of sleep disorders and sleep problems within this population. The survey also included a section on other chronic health conditions, including gout. Age, sex, body mass index, and alcohol consumption were recorded. A possible undiagnosed OSA was determined through self-reported loud snoring and observed apnea.

A total of 1948 (95.3%) participants were included in the analysis, of whom 126 (6.5%) had a diagnosis of gout and 124 (6.4%) had sleep apnea. Patients with gout were more likely to be male than female (11.2% vs 2.0%, respectively) and had higher rates of comorbidities, such as diabetes, obesity, heart disease, and high blood pressure.

Participants with either OSA symptoms or doctor diagnosed OSA were 2.6 and 2.8 times more likely to have a concurrent gout diagnosis. Those with gout were 2.5 times more likely to experience restless leg syndrome and 2 times more likely to have anxiety related to sleep when compared with other respondents (31.9% vs 23.5%, respectively). They were also 1.6 times more likely to discuss these concerns with their physician than patients without gout (38.9% vs 28.5%, respectively).

The percentage of respondents with gout who felt they regularly achieved adequate sleep was not significantly different than those without gout. However, 15% of respondents with gout reported restless leg syndrome, compared with only 6.7% of participants without gout.

The study was strengthened by the large sample size that aligned to Australia’s general population. The cross-sectional design of the study was limiting as investigators were not able to comment on causation. Further, recent data has shown that after adjusting for factors such as renal function, heart failure, and diuretic usage, the link between gout and sleep apnea was no longer associated with male gender. As the information in this study was limited to questions asked in the survey, investigators were not able to adjust for renal function. Lastly, there may be an unknown risk factor for both gout and sleep apnea that was not addressed, which may cause potential bias in the results.

“Our study has highlighted that sleep disorders and gout are common and frequently comorbid in the Australian population. Sleep apnea and gout are both associated with significant cardiovascular morbidity and mortality, but are also treatable,” investigators concluded. “An awareness of the co-existence of both conditions should lead to increased screening and appropriate treatment tailored to patient needs. Further research is required to delineate the nature of the relationship between conditions, and also to establish if treatment of one condition may influence the trajectory of the other condition.”

New-Tolley J, Reynolds AC, Appleton SL, et al. Sleep disorders and gout in Australian adults. 

. 2021;5(1):30. Published 2021 Aug 28. doi:10.1186/s41927-021-00199-y

Obstructive Sleep Apnea Linked to Gout

Rheumatology Network Roundup: COVID-19

Catch up on Rheumatology Network's most recent highlights in COVID-19 news. 

Rheumatology Network Spotlight: COVID-19

While etanercept is used more frequently in patients with juvenile idiopathic arthritis (JIA), the efficacy, safety, and occurrence of adverse events (AEs) were similar when compared with biosimilars, according to a study published in 

 As etanercept is more expensive, investigators urge switching to biosimilars in pediatric patients whenever possible.

“For the last 20 years, etanercept [a tumor necrosis factor α (TNFα) inhibitor] has been successfully used in clinical practice,” investigators explained. “However, the high costs of biologics prevent their use as a first-line therapy despite their favorable efficacy and tolerability.”

Patents with JIA who started treatment after January 1, 2017, were included in the study using data collected from the German BIKER registry (Biologics in Pediatric Rheumatology Registry). Investigators focused on patients younger than 18 at baseline being treated with etanercept or with etanercept biosimilars, Benepali and Erelzi. Eligible participants either began treatment on etanercept, a biosimilar, or switched to a biosimilar during therapy. Disease activity and safety were compared as separate components.

Efficacy was measured using the Juvenile Arthritis Disease Activity Score (JADAS-10) and the Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI). Disease activity was assessed at baseline and subsequent follow-ups and rated on a visual analog scale (VAS). Safety was determined by AE reports and discontinuation rates between the 2 groups were also analyzed.

A total of 348 patients were observed, with 293 in the etanercept cohort and 55 in the biosimilar cohort. Additionally, another 57 patients switched to a biosimilar from etanercept throughout their course of therapy. Patients who received a biosimilar skewed older and had received another biologic as a premedication.

There were no significant differences between patients receiving either etanercept or a biosimilar. Disease activity at baseline and at the final follow-up were similar in both groups. Additionally, disease activity remained the same in patients who were initially treated with etanercept before switching to a biosimilar.

AEs were most frequently cited as upper respiratory tract infections, reactions at the injection site, and gastrointestinal disorders. When AE rates per 100 patient-years were examined, the biosimilar cohort had a larger proportion of AEs when compared with the etanercept cohort, mainly due to local reactions (20% vs 6.8%, respectively). However, this did not impact adherence rates. AE frequencies per patient showed no significant difference in either group. Of the 19 severe AEs that required hospitalization, there were no significant differences in occurrence rate.

In the biosimilar cohort, 29.1% (n = 16) discontinued therapy, compared with 37.2% (n = 109) in the etanercept cohort. Reasons included remission, lack of efficacy, or experiencing AEs. In the group that switched to a biosimilar, 8 out of 57 patients discontinued treatment, with 50% of these achieving remission.

The much smaller number of patients in the biosimilar cohort limits the study and may reduce statistical reliability of the results. As many centers participate in the BIKER registry, there is a possibility that the reporting behavior of AEs may differ between rheumatologists and clinics. Another potential limitation is that patients were not randomly selected between the two cohorts and differed in their characteristics. However, the differences focused on age at therapy start and number of previously received biologics, so investigators are confident in the comparability of the groups.

“In accordance with the current literature, there are thus no medical concerns for increased use of the biosimilars Benepali and Erelzi,” investigators concluded. “Such increased use is particularly recommended considering the very high costs and growing inequality in access to treatment with biologics.”

Thiele F, Klein A, Hospach A, et al. Efficacy and Safety of Etanercept Biosimilars Compared With the Originator for Treatment of Juvenile Arthritis: A Prospective Observational Study [published online ahead of print, 2021 Aug 27]. 

. 2021;10.1002/acr2.11325. doi:10.1002/acr2.11325

Disease activity, safety, and the occurrence of adverse events were similar in patients with juvenile idiopathic arthritis receiving either etanercept or the biosimilars Benepali and Erelzi. 

Comparing Efficacy and Safety of Etanercept and Biosimilars in Patients With Juvenile Idiopathic Arthritis 

Rheumatology Network sat down with Philip Conaghan, MBBS, PhD, to discuss his 

World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases 

presentation entitled, “Meaningful Improvements in WOMAC Pain and Physical Function in 3 Phase 3 Trials of Tanezumab in Patients With Moderate-to-Severe Osteoarthritis: A Responder Analysis.” Dr. Conaghan is Professor of Muskuloskeletal Medicine at the University of Leeds. He explains the key takeaway points from his presentation, the study designs of the phase 3 trials, and the clinical significance of these results.

To begin, what are the key takeaway points from your presentation?

 I think the key point is we've been used to data coming out about monoclonal antibodies to new growth factor for some time. And questions about its efficacy have been raised at different times, especially as doses were reduced to minimize side effects. So, the key message to come out of this was based on work we've done previously showing that a 1 point, or 15%, improvement in WOMAC pain and in physical function (minimally clinically important differences for patients). We wanted to see how well tanezumab at 2.5 or 5 milligrams, as it was used in trials, how well they performed in achieving those levels of 1 point, or 15%, improvement for both pain and physical function.

What were the study designs of the 3 phase 3 trials?

So, people will be familiar with these trials. There were 2 big trials that were randomized control trials with 3.5 or 5 milligrams versus placebo. And there were 230 to 280 people per arm in those trials. And in the third trial, there was tanezumab 2.5, or 5 verses a non-steroidal anti-inflammatory drug (NSAID), so that's a longer-term trial. The others were shorter term studies with shorter term primary endpoints. The other was a longer-term trial. And it's important to realize it was against an active control. So, it wasn't a placebo-controlled study. So, different design for that. But it still allows us to compare the patients achieving meaningful pain and function response, even though it was an inside comparative trial.

And what were the results of these studies?

 What the results showed is that we see significant improvements for the tanezumab 2.5, and 5 milligram groups for both the randomized control trials, or at least for the 2.5, stepping up to 5 at second dose in 1 of those studies. Those patients had significant improvement for people in proportions achieving minimally meaningful improvements. And I've got to be very careful how I say those phrases. So, these are patients achieving minimally meaningful improvements for WOMAC pain and function. So that was for the 2 randomized trials and for the trial against placebo, the proportions of patients, meeting the thresholds to that minimally meaningful improvement for pain and function was similar for tanezumab and NSAIDs. So that's very comforting to those of us who've been using NSAIDs for a long period of time.

Were you surprised by the results of the studies?

Not really, I think for a long time, we've struggled with understanding what's an important difference. Most trials compare group level differences; we try to see how much is in this group versus how much is in the placebo group. And that's often hard to understand between group differences. It's often a bit easier to understand minimal clinically important differences at the individual patient level. And those figures have been around forever. Saying that a 30% change is 1 level of change that patients can recognize. As I said in earlier work, we showed that a 15% change was also probably the minimal, meaningful clinical difference that we could determine. I think the third study I mentioned is actually most reassuring when trying to understand new therapies withdrawn or understand how they compare against their current standard of care. And oral NSAIDs remain our current standard of care.

What is the clinical significance of these results?

I think the important issue is that this drug looks like it's got effective clinical relief for patients in terms of pain and in terms of function. And that's really important for a field like osteoarthritis, where we have so few options and indeed, less options than we had 10 years ago. So, I think we desperately need some new therapies that will work to reduce people's pain.

Videos

Philip Conaghan, MBBS, PhD, discusses his presentation entitled, “Meaningful Improvements in WOMAC Pain and Physical Function in 3 Phase 3 Trials of Tanezumab in Patients With Moderate-to-Severe Osteoarthritis: A Responder Analysis.” 

Philip Conaghan, MBBS, PhD: Efficacy of Tanezumab in Patients With Osteoarthritis 

Most total knee replacement (TKR) recipients recognized the importance of physical activity (PA) and were willing to use activity monitors to increase activity levels after surgery, motivated by both external and internal factors, according to a study published in 

“PA offers many health benefits, including prevention and management of chronic disease, delay of functional decline and disability onset, and improved quality of life (QoL),” investigators stated. “Despite these benefits, participation in PA is low, both within the general population and among individuals with osteoarthritis (OA).”

In this qualitative study, patients were recruited from the Orthopedic and Arthritis Center at Brigham and Women’s Hospital (BWH) using electronic medical records. Investigators narrowed the search to include patients who either had a TKR scheduled within the next 6 weeks or recently underwent surgery. 

A survey was designed to determine the role of PA in their daily lives and to identify factors that would motivate or deter them from wearing activity monitors and engaging in regular PA. Identifying these goals may help rheumatologists create strategies to increase activity levels among their patients.

After eligibility assessments, 27 participants were included in the study. Ten of the patients were interviewed pre-surgery and 17 were interviewed afterwards. The mean age was 66 years, 89% were white, and the majority of patients were women (16 vs 11, respectively).

In the second phase of the study, 3 co-authors determined patterns and themes from the responses and created a thematic map to illustrate the relationship between themes.

1: Exercise benefits both physical and mental health

Patients reported exercise and diet are necessary tools to improve physical health, aid in weight loss, and maintain good mental health.

2: Pain and limited function hinders daily life

The ability to socialize, pursue hobbies, climb-stairs, clean, and shop were impacted by their physical limitations.

Participants believed that the surgery would enable them to resume activities they valued.

4: Situational factors impact levels of PA

Examples of situational factors included the COVID-19 pandemic, weather, amount of free time, and other health factors.

5: Friends and family encourage use of activity monitors

Those with more active friends and family were more likely to become more physically active. Additionally, less tech-savvy participants were more willing to use a monitor when they had someone who could help set it up for them.

6: Prior activity levels influence post-surgery goals

Most patients wanted to achieve or exceed pre-development of advanced OA activity levels.

7: Activity monitors motivate patients to achieve and set goals

Patients reported that tracking steps promotes physical activity.

8: Different incentives work for different individuals

Some of the factors included financial, pleasing their rheumatologist, self-motivation, and reminders.

9: Participants had a generally favorable perception of activity monitors and activity tracking

Tracking PA metrics would help them successfully recover as well as monitor and increase PA levels.

A limitation of the study was the lack of objective data to determine PA levels. Generalizability may be reduced as all patients came from a single medical center. Further, participants were not asked about environmental or systemic barriers to exercise.

“Individuals who undergo TKR are motivated in large part by an inability to engage in valued activities because of knee pain and impaired function,” investigators concluded. “Future research should investigate whether providing patients with activity monitors before and after surgery could help them set realistic goals, monitor their progress, and increase their PA levels. Lastly, clinicians and researchers may consider personalizing interventions, including the type of PA monitor, based on patient preferences, goals, and values.”

Arant KR, Zimmerman ZE, Bensen GP, Losina E, Katz JN. Perceptions of Physical Activity and the Use of Activity Monitors to Increase Activity Levels in Patients Undergoing Total Knee Replacement [published online ahead of print, 2021 Aug 19]. 

. 2021;10.1002/acr2.11324. doi:10.1002/acr2.11324

Despite the benefits of physical activity, participation is low, both within the general population and among individuals with osteoarthritis (OA). Activity monitors may aid in increasing these levels in patients with OA as well as in those requiring a total knee replacement. 