Lana Dykes

Investigators note that these findings emphasize "the magnitude of the potential methotrexate access problem. In the short interval since the ruling, there has been a wide fluctuation in the state-by-state legal status of abortion, which could generate confusion among healthcare providers and potentially affect the accessibility of vital medications for patients with rheumatologic conditions.”

We sat down with Kazuki Yoshia, MD, MPH, ScD, Director of Rheumatology and Principal Epidemiologist at OM1, to discuss the findings of the study and the next steps for his team.

 What were the methods your team used to identify patients treated with methotrexate?

 We used our nation-wide data network (OM1 Real-World Data Cloud) to identify patients who used methotrexate in the last 2 years (n = 139, 288). Among them, we excluded those with cancer and ectopic pregnancy diagnoses. We deemed the remaining users of methotrexate (82%, n = 114,787) as methotrexate users who were using methotrexate for rheumatic and immunological conditions.

 Your results stated that in mid-September, approximately half (53%) of patients prescribed methotrexate are residing in states where abortion is banned or restricted. How has this impacted patients/access to the drug?

 of existing methotrexate users. At this point, we have NOT directly studied the ground-level impact on the methotrexate access (for example, prescription declined, reduced use in methotrexate, etc).

 What is the clinical significance of your findings?

 Our result is important in that (a) we clarified most of the methotrexate use (82%) is for rheumatic and immunological conditions for which continued life-long care is essential and (b) substantial proportion of patients are female (73%, n = 83,517) of whom 23% (n = 19,000) were of reproductive age (and likely to be susceptible to abortion-policy-related methotrexate access issues).

 Were there any strengths or limitations that you’d like to discuss?

 The strength of our study is the nation-wide nature of our data network, making it possible to quantify the potential impact of this Supreme Court ruling on methotrexate access. The main limitation is that what we studied is the distribution of existing methotrexate users, rather than changes in methotrexate use after the ruling.

 Does your team plan on doing any further research on this topic?

 One potential direction is to follow the utilization of methotrexate over time before and after the ruling in relation to the state-level policy.

Starzyk K, Hoffman V, Su Z, et al. Over Half of Methotrexate Users Reside in States in Which the Overturning of Roe v. Wade Can Jeopardize Access to Medications with Abortifacient Potential [published online ahead of print, 2022 Nov 11]. 

. 2022;10.1002/art.42398. doi:10.1002/art.42398

Articles

In the wake of the Supreme Court’s decision to overturn Roe v Wade, results of a recent study indicated that more than half of female patients treated with methotrexate, a commonly-prescribed drug used to manage rheumatic diseases, lived in states with abortion restrictions or bans.

Methotrexate access for rheumatoid arthritis in the post-Roe v Wade era

The volume of fat mass, as analyzed by a Principal Component Analysis (PCA), was shown to negatively modulate the severity of fibromyalgia syndrome (FMS), according to a study published in Reumatología Clínica.1 Investigators urge clinicians to evaluate body composition as part of the basic clinical approach for the treatment of this patient population.

“Since at least part of the pathogenesis of FM appears to be influenced by impaired regulation of pain modulating cytokines,both centrally and peripherally, the hypothesis that body composition can modulate the symptomatic context of fibromyalgia syndrome is perfectly plausible, although the results coming from studies devoted to the topic are contradictory,” investigators stated.

In this observational, quantitative, cross-sectional study, the association between type of body composition and FMS was evaluated using 43 women with clinically diagnosed FMS, per the American College of Rheumatology (ACR) 2010 criteria.

Clinical outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), Symptom Severity Scale (SSS), and the Widespread Pain Index (WPI). Anthropometric data was categorized into PCA-

. Patients were also classified into high and low categories for each clinical indicator, which were used in the binomial logistic regression (BLR) models. Inclusion criteria included female sex, aged 18 years or older, with a clinical diagnosis of fibromyalgia (FM). Patients were selected through the Rheumatology outpatient clinic at the Yucatán Peninsula’s High Specialties Regional Hospital.

The median age of patients was 52.7 (± 11.3 years) years and had an average disease duration of 53.6 ± 54 months. Most patients were currently receiving some form of medication, including nonsteroidal anti-inflammatory drugs (NSAIDs) (65%, n = 30), opioids (28%, n = 13), and benzodiazepines or antidepressants (62%, n = 27, combined). Nearly all patients were classified as overweight or obese (90.7%), and most had 1 or more comorbidity (62.7%).

A positive correlation was shown between PCA-

 and both WPI (r = 0.326, P = .043) and FIQ (r = 0.325, 

 = .044). There was a negative correlation between PCA-

 was a significant predictor of high WPI (OR = 2.477, 

 was an inversely significant predictor of high SSS (OR = 0.303, 

“Our results strongly suggest that hyper-adiposity states may negatively modulate the clinical severity in FM,” investigators concluded. “Thus, body composition appraisal must be part of the global assessment of FM patients, with mandatory nutritional counseling, and special emphasis in the diet, from which patients can see benefits ranging from reduced anxiety symptoms, mood disturbance, and even disappointment with body image.”

This article originally appeared on Rheumatology Network®.

Álvarez-Nemegyei J, Pacheco-Pantoja EL, Olán-Centeno LJ, Angulo-Ramírez A, Rodríguez-Magaña FE, Aranda-Muiña JF. Association between fibromyalgia syndrome clinical severity and body composition. A principal component analysis. 

. 2022;18(9):538-545. doi:10.1016/j.reumae.2021.09.008

The association between type of body composition and fibromyalgia was evaluated using 43 women with clinically diagnosed fibromyalgia.

Volume of fat mass negatively impacts severity of fibromyalgia

Pregnant patients with psoriatic arthritis (PsA), although not pregnant women with axial spondyloarthritis (axSpA), were at an elevated risk of developing pre-eclampsia. In patients with rheumatoid arthritis (RA), risk factors included receiving combination therapy and high disease load during pregnancy, according to a study published in 

“RA, AxSpA, and PsA affect women in their reproductive years,” investigators explained. “Previous studies have indicated associations between these disorders and adverse pregnancy outcomes, for example, preterm birth, small for gestational age, and caesarean sections. The potential impact of disease activity and use of medication during pregnancy are causes for concern.”

Singleton pregnancies of patients with rheumatic diseases were identified via linking medical birth registers to Swedish Rheumatology Quality Register (SRQ) and Danish (DANBIO) rheumatology registries. Controls were then matched 1:10 for age, similarity, and birth year. Information on treatment 9 months prior to and during pregnancy, as well as functional status and disease activity during pregnancy, was collected. Only pregnancies of women registered in SRQ or DANIBO for 6 or more months prior to conception were included in the study.

Pregnant patients with RA, PsA, and AxSpA were compared with the control group and risks of pre-eclampsia, defined as new-onset hypertension and multiorgan failure, were estimated both overall and by disease load and antirheumatic treatment, which included corticosteroids, biological disease-modifying antirheumatic drugs (bDMARDs), and conventional synthetic DMARDs (csDMARDs), both as monotherapy and combination therapy. The disease load was analyzed using the Health Assessment Questionnaire ≥1, Disease Activity Score in 28 joints (DAS28-CRP) ≥3.2, and C-reactive protein (CRP) ≥10.

Ultimately, 69 (3.9%) patients with RA (n = 1739), 34 (4.2%) patients with axSpA (n = 819), and 26 (5.3%) patients with PsA (n = 489) experienced pre-eclampsia events. Patients with PsA were more likely to be less educated, smokers, and obese. The PsA cohort had an 85% increased risk of developing pre-eclampsia when compared with controls (adjusted odds ratio [aOR] 1.85 (1.10 to 3.12). The corresponding aOR for axSpA patients was 1.17 (95% CI 0.76 to 1.78). Risk was only slightly increased in patients with RA (1.27; 0.96 to 1.67).

Monotherapy prior to pregnancy was linked to pre-eclampsia in the PsA group (2.72; 1.4 to 5.13). Patients with RA receiving combination therapy both before and during pregnancy had a higher risk of developing pre-eclampsia (1.59; 1.07 to 2.37 and 1.53; 0.97 to 2.39, respectively). Additionally, a high disease load doubled the risk of developing pre-eclampsia in the RA cohort (aOR 1.96; 1.26 to 3.04).

Strengths include the large size of pregnancy cohorts from comprehensive Scandinavian registries, which allowed investigators to eliminate recall bias and adjust for covariates. Multiple data sources were combined to ensure the most accurate treatment information and disease activity was included, which had not been previously possible.

However, the number of pre-eclampsia events were low, thus reducing statistical power. Further, disease activity and treatment information were not available in a substantial proportion of pregnancies. Future studies focusing on a close follow-up of women before and early in pregnancy would be beneficial.

“From a clinical perspective, our findings add to the field of knowledge, by informing clinicians of the underlying risk of pre-eclampsia in these patient populations and by emphasizing the importance of monitoring women with, in particular, RA and PsA regarding this risk,” investigators concluded.

Secher AEP, Granath F, Glintborg B, Rom A, Hetland ML, Hellgren K. Risk of pre-eclampsia and impact of disease activity and antirheumatic treatment in women with rheumatoid arthritis, axial spondylarthritis and psoriatic arthritis: a collaborative matched cohort study from Sweden and Denmark. 

. 2022;8(2):e002445. doi:10.1136/rmdopen-2022-002445


This article originally appeared on Rheumatology Network®.

Previous studies have suggested a connection between rheumatic diseases, which often affect women in their reproductive years, and adverse pregnancy outcomes, such as pre-eclampsia.

Increased risk of pre-eclampsia reported in patients with PsA

Patients with rheumatoid arthritis (RA) and those at-risk of developing RA had higher levels of antibodies against a gut protein expressed by 

 when compared with a control group, according to a study published in 

.1 Results indicate a potential role for 

 in the evolution of preclinical RA and the pathogenesis of synovitis.

“Manifestation of systemic autoantibodies in serum prior to inflammation in joints, the well-established primary tissue target of the disease, suggests initiation of the autoimmune process elsewhere,” investigators stated. “Mucosal sites such as the periodontium, lungs, gut, and vaginal tract have garnered attention as initiating sites for the autoimmune process in RA. Recent developments in the identification and categorization of bacterial commensals and pathobionts at mucosal sites have helped to advance our understanding of the immune consequences when dysbiosis exists.”

Participants were chosen from the multicenter, longitudinal Studies of Etiology of Rheumatoid Arthritis (SERA) study. At-risk participants, patients with early RA (< 1 year), those with established RA, and healthy controls were included in the study. Serum levels of immunoglobulin A (IgA) and immunoglobulin G (IgG) anti-

-p27 were analyzed and compared with controls. Anti-

p27 antibodies were evaluated in participants stratified by RA-related autoantibody status. Questionnaires evaluated demographics, history of disease in the participant as well as their family, and environmental exposures, both past and present. A 68-joint examination was performed in the at-risk patients and control participants to confirm the absence of RA and confirm the presence of inflammatory arthritis (IA) in those who transitioned to disease.

Patients with RA had significantly higher levels of IgA anti-

-p27 antibodies and trended towards higher levels of IgG anti-

-p27 antibodies when compared with matched controls. Patients with early RA had higher median values of IgG anti-

-p27 when compared with those with established RA. However, median values of IgA anti-

-p27 were statistically significantly higher in participants with established RA when compared with matched controls.

In autoantibody specific analyses, participants at-risk of developing RA with anti-cyclic citrullinated peptide (CPP) autoantibodies were more likely to present with an increased level of IgG anti-

-p27; however, this did not carry over to those with rheumatoid factor (RF). Patients with RA who were CCP+/RF+ reported significantly increased levels of IgA anti-Pc-p27 antibodies and a trend toward levels of IgG anti-

-p27 antibodies when compared with the control group.

 immune response was recognized based on reactivity with only 1 protein, 

-p27, which may have limited the ability to detect reactivity with this microbe and negatively impacted the significance in some adjusted analyses. Further, pathogenesis of this protein may have only had immunologic relevance in a subset of patients with RA. It remains unclear as to why those with the most significant IgA response to 

-p27 was seen in patients with established RA instead of those with early RA. However, investigators were able to show statistically significant associations with IgA anti-

-p27 antibody responses in patients with RA and higher levels of IgG anti-

-p27 in the CCP+ at-risk participants, as well as those with early RA.

“Our hope is that these findings can help to further elucidate the complex etiologic role of bacterial commensals in people who are at-risk of developing RA and in those with RA so that targeted therapies can be developed with the goals of providing better treatment and ultimately, prevention of the disease,” corresponding investigator Jennifer A. Seifert, MPH, of the University of Colorado Denver, concluded.

Seifert JA, Bemis EA, Ramsden K, et al. Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis [published online ahead of print, 2022 Oct 19]. 

. 2022;10.1002/art.42370. doi:10.1002/art.42370

Patients with rheumatoid arthritis had significantly higher levels of IgA anti-Pc-p27 antibodies and higher levels of IgG anti-Pc-p27 antibodies when compared with healthy controls.

Elevated immune response to gut bacterial protein associated with rheumatoid arthritis

Holistic, collaborative, multidisciplinary, and integrated communication between physicians and women of childbearing age is lacking, according to a study published in 

 Medical treatment and family planning, particularly among women of childbearing age with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), should be considered within this patient population. Patient-centered care including reproductive choices should be integrated as a part of routine clinical practice.

“The proportion of women being treated with biologics is growing,” investigators explained. “However, data on treatment recommendation awareness among treating physicians and women who are considering pregnancy and family planning are limited.”

An English-language, 55-question survey was developed to identify the current practices of physicians regarding the reproductive health needs of women with RA, PsA, and psoriasis in the Czech Republic, Slovakia, and Hungary. The questionnaire was designed to simultaneously elicit spontaneity of physicians while allowing for the processing of responses, mutual comparison, and overall assessment. The survey obtained information from 120 physicians, including 82 rheumatologists and 38 dermatologists.

Female patients of reproductive age (aged 18 to 45 years) with moderate-to-severe disease encompassed 10-30% of all respondents. Roughly two-thirds of physicians discussed family planning with their patients when making the diagnosis. Rheumatologists collaborated with other specialists more frequently when compared with dermatologists and gynecologist/obstetricians. Pregnancy effects were the top concern for female patients.

Approximately half of the rheumatologists revised treatment 6 months prior to when the patient planned on becoming pregnant (44% [n = 36/81]). However, dermatologists acted much sooner (26% [n = 10/38]), acting 2 to 3 years prior planned parenthood. While rheumatologists selected systemic glucocorticoids as firs-line treatment to counteract pregnancy flares, dermatologists preferred topical corticosteroids.

Although gender alone did not influence treatment choice in 11% of dermatologists and 39% of rheumatologists, all dermatologists and 96% of rheumatologists were influenced by the patient’s fertility and pregnancy. Disease severity and uncontrolled disease were the main risk factors linked to conception in this patient population. In fact, 53% of dermatologists and 79% of rheumatologists believed that poor disease control was associated with poor pregnancy outcomes. Of the most valuable sources of information as determined by physicians, congresses and interdisciplinary forums were the most highly rated. Patient education and collaboration were noted as key factors in reducing unplanned pregnancies.

A cross-border investigation, from the perspective of both rheumatologist and dermatologist, strengthened the study. However, investigators did not evaluate or categorize the individual physicians’ level of experience with biologics or reproductive health and instead based data on actual clinic experience. Investigators theorize that those who have had more exposure to this approach would be more willing to utilize it. The lack of formal survey validation, and the fact that the survey was provided in English, further limits the study.

“To improve the reproductive health of sexually active women of childbearing age in Central Europe who have chronic inflammatory diseases (CID), rheumatologists and dermatologists must improve their education and work with other specialists,” investigators concluded. “More timely discussions with women of reproductive age and family planning are needed to educate them about the disease's effects on their childbearing potential and the selection of treatment options based on their reproductive goals. Best practices in patient-centered care must consider each patient's reproductive decisions in their treatment planning to give the best patient-centered care.”

This article originally appeared on Rheumatology Network®. 

Olejárová M, Macejová Ž, Gkalpakiotis S, Procházková L, Tóth Z, Prágr P. Reproductive Healthcare in Women with Rheumatoid Arthritis and Psoriatic Diseases in Routine Clinical Practice: Survey Results of Rheumatologists and Dermatologists [published online ahead of print, 2022 Sep 24]. Rheumatol Ther. 2022;10.1007/s40744-022-00488-z. doi:10.1007/s40744-022-00488-z

Although the proportion of women treated with biologics continues to grow, data on treatment recommendations among both physicians and female patients of childbearing age remain limited.

Survey addresses concerns regarding reproductive health care communication in women with RA, PsA

Our sister publication, Rheumatology Network,

 interviewed Bonnie L Bermas, MD, to discuss the ways in which the Supreme Court decision to overturn Roe v Wade, a ruling that had guaranteed the right to abortion in the United States since 1973, will change the way rheumatologists are able to care for their patients. She emphasizes the negative effects this legislation will have on marginalized populations, explains how the ruling will impact pregnancy in patients with rheumatic disease, and what rheumatologists need to know moving forward. Bermas, Professor in the Department of Internal Medicine at UTSouthwestern Medical Center, co-authored the article “Overturning Roe v. Wade: Toppling the Practice of Rheumatology,” published in 

 What was the motivation for you and your team to want to address the recent decision to overturn Roe v Wade?

 We as rheumatologists, and in particular this collection of rheumatologists, amongst many other rheumatologists, have an interest in reproductive issues in our rheumatic disease patients. We think about this a lot because we care for a lot of patients who are in their reproductive health years. This ruling has tremendous impact on our patients. Our motivation was the impact it has in our patients.

 Overturning Roe v Wade will obviously affect patients with a constellation of rheumatic diseases. However, it might disproportionately affect women with lupus, who are often diagnosed in their reproductive years. What are your thoughts on how this decision might impact this particular patient population and pregnancy in general?

 We know that lupus pregnancies are high risk pregnancies, and they have a higher incidence of adverse pregnancy outcomes both amongst the mothers and the developing fetus and infant. One of the crucial things in controlling those or preventing adverse pregnancy outcomes, which can be progression of disease or an adverse pregnancy outcome in the fetus, is that the disease really needs to be under good control. And, as you know, no contraception is perfect. Inadvertent pregnancies do occur, or people will get pregnant when their disease is active. And that can be really detrimental and dangerous. The maternal mortality rate for lupus patients is during pregnancy is significantly higher than in general population.

Our patients are frequently treated with medications that can cause birth defects. And so that is another issue in terms of this rule. Also, lupus disproportionately impacts minoritized patient populations. Those patient populations, unfortunately, often live in the states that have the most restrictive abortion laws, and some of these patients may not have the resources to travel out of state if they need to have a pregnancy termination.

 What are some of the potential outcomes of this legislation on the practice of rheumatology in terms of prescribing medications and treating patients?

 That's a really important point. The first thing is that we try to encourage rheumatologists to tell their patients up front about the risks of unplanned pregnancies and emphasize the importance of contraception in women who are sexually active. We need to make sure that we're discussing this a lot with our patients.

The second thing is there are going to be providers who are possibly reticent to prescribe teratogenic medications to their patients. The 2 most common medicines that would fall under that category would be methotrexate and Mycophenolate Mofetil. Methotrexate is the first drug of choice for the treatment of inflammatory arthritis issues such as juvenile idiopathic arthritis and rheumatoid arthritis. Mycophenolate Mofetil is one of our key medications in treating lupus and lupus kidney disease. You can imagine that there will be some hesitancy in prescribing these medications. Potentially, we're talking about rheumatologists not prescribing the best medication for their patients.

 What do rheumatologists need to know moving forward?

 They need to know that pregnancy across all rheumatic diseases does best when pregnancies are planned. So that means really ramping up our understanding of what the most effective contraceptive methods are. And it is also about asking if patients are sexually active, if they're planning to get pregnant, and referring them appropriately for contraception if they're not already on contraception. Providers also need to understand which medications are teratogenic.

 Is there anything else that you would like to add before we wrap up?

 What really motivated us to write this is that this ruling is not good for patient care and it's not good for our patients. Like the vast majority of providers, we care about our patients and their wellbeing. So, it's pretty devastating to feel that there's been a politicized ruling that is going to negatively impact our ability to provide our patients with the best care.

Bonnie L Bermas, MD, emphasizes the negative effects this legislation will have on marginalized populations and explains how the ruling will impact pregnancy in patients with rheumatic disease.

Lana Dykes

Articles

Methotrexate access for rheumatoid arthritis in the post-Roe v Wade era

Volume of fat mass negatively impacts severity of fibromyalgia

Increased risk of pre-eclampsia reported in patients with PsA

Elevated immune response to gut bacterial protein associated with rheumatoid arthritis

Survey addresses concerns regarding reproductive health care communication in women with RA, PsA

How will overturning Roe v Wade affect rheumatology?