Obesity has reached epidemic levels in the United States, afflicting more than 93.3 million individuals, or 39.8% of the total population. Additionally, another one-third of American adults are considered to be overweight, which means that more than 2 in 3 adults in the United States carry excess weight.¹

Overweight or obese are described as weighing more than what is considered healthy for a given height. Body mass index (BMI), while not a direct measure of body fat, is commonly used as a screening tool for overweight or obesity and has been found to be strongly correlated with weight-related adverse outcomes. Individuals with BMIs between 25.0 and 30 kg/m² are considered overweight, while those with BMIs ≥30 kg/m2 are considered to be obese. Obesity is often further categorized into Class 1 (30-35 kg/m²), Class 2 (35-40 kg/m²), and Class 3 (≥40 kg/m²).²

Both overweight and obesity have been associated with a number of disease states, such as hypertension, dyslipidemia, heart disease and stroke, type 2 diabetes, sleep apnea, various cancers, and osteoarthritis. They also have significant negative impacts on an individual’s daily functioning, pain level, and quality of life.^3,4 While not yet conclusive, findings in the literature suggest that rheumatoid arthritis (RA) should likely be added to the list of disease states linked to overweight and obesity. In a 2013 study, a team of researchers at the Mayo Clinic found that individuals with obesity were at a 25% increased risk of developing RA compared with non-obese individuals.⁵ A recent systematic review supports these findings; compared with normal weight individuals, individuals who were overweight or obese had a 15% and 31% increased risk for developing RA, respectively.⁶

The incidence of overweight and obesity in patients with RA appears to track comparably with or slightly higher than the general population. Data from the Canadian Early Arthritis Cohort (N=982) found that 32% of patients with RA had a healthy BMI, 35% were overweight, and 33% were obese.⁷ This compares with overall rates of overweight and obesity in Canada of 36% and 26%, respectively.⁸

Most research shows that the presence of obesity in patients with RA is associated with more significant disease activity, greater disability, greater pain, impaired quality of life, poorer general health, and reduced response to treatment.^9,10 There are, however, some studies showing that obesity appears to provide a protective effect in some patients with RA, with patients with obesity having radiographic evidence of less joint damage over time, suggesting less destructive inflammatory disease.^11,12 Past studies have also suggested that the presence of obesity among RA patients is associated with decreased mortality compared with RA patients with a normal BMI; however, some current data challenges the notion of an “obesity paradox” in patients with RA. This will be explored in greater detail later in the issue.

Simply based on the presence of their disease, patients with RA are already at increased risk for cardiovascular morbidity and mortality compared with the general population.¹³ This is in part due to unfavorable body composition changes (reduced lean muscle mass and increased fat mass) that occur as a result of the disease process.¹⁴ In addition, excess weight in patients with RA also tends to develop as visceral – as opposed to subcutaneous – abdominal fat, contributing to higher systemic inflammatory burden.¹⁵ Given that muscle is heavier than fat, BMI may actually underestimate overweight and obesity in patients with RA. As such, RA-specific BMI cut-off points (23 kg/m² for overweight and 28 kg/m²) have been proposed for consideration in this population.¹⁶

Individuals with RA who are overweight/obese and have intentionally lost weight demonstrate improvements in disease severity and response to RA-related medications as well as improvements in physical function.^17,18 Intentional weight loss is defined as a voluntary decrease in body weight using strategies that may include lifestyle interventions, weight loss medications, and weight loss surgery. In contrast, unintentional or unexplained weight loss may reflect an underlying medical disorder or be rooted in other nonmedical causes.^19,20 Beyond the myriad health benefits associated with weight loss (e.g., reduced risk of cardiovascular disease, metabolic syndrome, osteoarthritis relief), the direct targeting of obesity itself as a therapeutic intervention for RA management holds merit as a potential additional tool for clinicians.¹⁷

Obesity and RA: What’s the Connection?

Whether excess weight predates the development of RA or the mechanisms that cause RA is not yet clear. However, it is highly plausible there is a link between obesity and the development of RA, given that obesity creates a state of systemic inflammation due to dysfunctional adipose tissue.^13,21 While a definitive mechanism to explain the association between obesity and RA has not yet been established, several potential mechanisms have been suggested.

Overweight and obesity reflect excess fat cell accumulation in adipose tissue. It is now recognized that white adipose tissue is a metabolically active tissue that produces and releases chemicals, many of which are pro-inflammatory, including cytokines (e.g., tumor necrosis factor [TNF]-alpha, interleukin-1, C-reactive protein [CRP], and interleukin-6) and adipokines (e.g., leptin, adiponectin, visfatin, and resistin).^5,13 Furthermore, the state of obesity promotes the production of apoptosis inhibitory macrophages, which are involved in the formation of autoantibodies.²² Both inflammatory cytokines and adipokines have been found to play a role in the pathogenesis of rheumatic diseases such as RA.⁵

Adipokines have captured significant interest due to their role in the development of RA as well as other conditions such as cardiovascular disease and metabolic syndrome.¹³ Adipokines have potent immune-modulatory properties that demonstrate both pro- and anti-inflammatory effects.²³ Many adipokines have been found to be elevated in patients with RA and are predominately associated with proinflammatory effects on synovium, bone, and cartilage.^13,23 In addition to promoting inflammation, adipokines cause dysregulation of T-helper 17 and T-regulatory cells, both key players in immune activation and self-tolerance.^22,24 Unlike other adipokines, adiponectin production decreases as individuals gain weight, which may help explain why overweight/obese individuals with RA demonstrate less joint damage compared to those without excess weight.^13,23

The contribution of vitamin D deficiency to the development of RA is also an area of active investigation, given that overweight/obese individuals often have low or deficient vitamin D levels.⁵ Lastly, obese individuals have higher levels of estrogens and androgen, both of which are thought to play a role in the development of RA.⁶

Excess Weight = More Active RA?

Obesity creates a systemic pro-inflammatory environment, which theoretically can contribute to more active disease.¹¹ However, it is not clear if patients with RA and obesity have a more severe disease course vs. a more severe disease experience since the state of obesity itself has been associated with more pain, comorbidity, and disability.¹² A large survey of more than 1 million individuals in the United States found that self-reported rates of pain increased with corresponding increases in BMI, with overweight individuals reporting 20% higher rates of pain within the last day compared with persons in the low-normal BMI group. Among those with obesity, individuals with Class 1, Class 2, and Class 3 obesity reported 68%, 136%, and 254% higher rates of a pain condition within the last day respectively compared with individuals with low-normal BMI.25 In addition, the presence of obesity has been found to be independently associated with impaired quality of life in patients with RA.²⁶

Patients with RA and overweight/obesity tend to experience more pain and disability, worse general health, and higher scores on measures of disease activity (e.g., Disease Activity Score in 28 Joints [DAS28]) compared to normal weight individuals.^11,27 It has been suggested that these observed increases in disease activity and disability may be due in part to the patient-reported subjective components of disease activity measures as well as the fact that higher BMIs are independently associated with elevated inflammatory markers (CRP and erythrocyte sedimentation rate [ESR]), particularly in women.^17,28,29 For instance, in one series, breakdown analysis of individual DAS28 score components indicated that increased BMI was associated with high visual analog scale (VAS)-pain scores, elevated ESR, and high levels of self-reported disability, but neither increased swollen or tender joint counts nor impaired quality of life.¹¹ Furthermore, radiographic evidence of joint damage in individuals with RA has been found to be inversely associated with obesity.^14,28 Conversely, recent data indicate patients with obesity show increased rates of synovial inflammation.³⁰

As such, it can be challenging to tease out whether scores on composite indices of disease activity reflect obesity itself, RA itself , or an exacerbation of RA by the presence of obesity.¹² It has been proposed that the use of RA disease activity measures that do not incorporate serum inflammatory markers—such as clinical disease activity index (CDAI)—may be helpful when comparing patients with RA and obesity to those without obesity.¹⁷ The influence of adiposity inflammatory marker levels carries potential implications for both diagnosing RA as well as monitoring response to therapy.

Do Commonly Used RA Medications Affect Weight?

For some medical conditions, the choice of medication can be influenced by the drug’s ability to alter weight. Type 2 diabetes is a classic example, with some classes of drugs associated with weight loss (e.g., glucagon-like peptide 1 receptor agonists), while others are associated with weight gain (e.g., insulin).³¹ For patients with RA, questions over weight changes secondary to disease-modifying anti-rheumatic drug (DMARD) therapy may also arise.

Results from a recent study found that various DMARD therapies had different impacts on body mass in patients with RA initiating DMARD therapy. Fluctuations in BMI 6 months following the date of prescription fill were assessed in 32,859 patients with RA who initiated treatment with methotrexate (MTX), prednisone, leflunomide, and/or a tumor necrosis factor inhibitor; many patients included in this study were receiving combination therapy. Overall, MTX, prednisone, and TNF inhibitors were independently associated with modest increases in BMI following 6 months of treatment, with the greatest increases in BMI seen with prednisone. MTX and TNF inhibitor use were associated with comparable gains. In contrast, patients receiving leflunomide were significantly more likely to lose weight, albeit a modest amount, compared with those receiving MTX. This finding is consistent with results from other studies in the literature that suggest prednisone, MTX, and TNF inhibitors are associated with modest weight gain, whereas leflunomide is associated with modest weight loss (see Figure 1).³²

Analysis of body composition changes in patients with RA receiving treatment with TNF inhibitors found that while TNF inhibitors were associated with increases in fat mass, adiposity, and android (visceral region) mass, they were also associated with decreases in lean mass.³³

Similarly, data indicate that use of non-TNF inhibitor biologic DMARDs in patients with RA may be associated with weight gain, although they have a different impact on body composition changes. For instance, one study evaluating changes from baseline in body composition following 12 months of treatment with tocilizumab (an IL-6 inhibitor) in 21 patients with active RA found that tocilizumab was associated with increases in body weight (mean increase: 1.9 kg) and BMI (mean increase: 1.2 kg/m2). Interestingly, fat composition (e.g., total fat mass, body fat percentage) did not increase. Instead, both total lean mass and fat free mass index increased, with significant gains in appendicular lean mass and skeletal muscle mass. At 1 year, changes in fat distribution were noted, with trunk/peripheral fat decreasing and subcutaneous fat increasing.³⁴

Definitive explanations for weight gain and loss seen with different DMARDs are lacking. Weight gain may reflect reduced inflammation and resting energy expenditure as well as weight gain secondary to steroid use, whereas weight loss with leflunomide may reflect drug side effects such as diarrhea, gastrointestinal distress, and decreased appetite.³²

The Potential Additive Effect of Treatment for Comorbidities

Individuals with overweight/obesity and RA often have weight-related comorbidities. One study found that, among patients with RA and obesity, 52% had hypertension and 68% had osteoarthritis,¹⁷ while another study found that osteoarthritis (26%), asthma (25%), and type 2 diabetes mellitus (25%) were the most common comorbidities in this population.³⁵ Patients may benefit from optimization of therapies related to the management of specific comorbidities that can impact weight.³⁶ For instance, the choice of antihyperglycemic therapies in individuals with type 2 diabetes or antihypertensives in patients with hypertension may affect weight gain or loss.^31,37

Excess Weight and Response to RA Treatment

Across the board, patients with RA and excess weight have been shown to have substantially impaired responses to therapy and a reduced likelihood of achieving sustained remission. In one series, being overweight or obese was shown to reduce the response to DMARD therapy and lowered the chance of achieving low disease activity by ~50% compared to normal weight individuals. The likelihood of achieving remission was also reduced among overweight and obese patients by 32% and 64%, respectively.³⁸

Similarly, another large study found that patients with obesity were 50% less likely to achieve remission after 1 year of TNF inhibitor therapy compared with non-obese patients; this was particularly notable in patients treated with infliximab.³⁹ A recent meta-analysis supports these findings, with the presence of obesity at the time of RA onset reducing the odds of achieving one-time and sustained remission by 43% and 51%, respectively.⁹ In contrast, other non-TNF inhibitor biologic therapies do not appear to be as impacted by the presence of excess weight. The frequency of remission seen with abatacept, tocilizumab, and rituximab therapy has not been observed to be significantly different between normal, overweight, and obese patients.⁴⁰

Explanations for how obesity affects response to RA therapy are elusive, but several reasons have been proposed, including the following:

1. The reduced efficacy of some biological and synthetic small molecule DMARDs may be due to increasing clearance with increasing body weight
2. Adipose tissue has been shown to induce biological resistance to anti-TNF therapy
3. Adipocytes may express high level of Fc receptors, potentially modulating the efficacy of biologic DMARDs containing an Fc component in their construct (the majority of biologic DMARDs fall into this category; certolizumab pegol is an exception).^15,41-43

BMI and Mortality Risk: The Obesity Paradox

One of the more interest phenomena in patients with RA is called the “obesity paradox.” In short, this describes the theory that higher BMI is inversely associated with reduced mortality. In several studies of patients with RA, obese patients have demonstrated a 26-67% decreased mortality compared with patients with a normal BMI. The pattern appears to be relatively linear, with underweight individuals having the highest mortality rates.^10,44

While the obesity paradox has gained popularity as a supposed phenomenon, more recent investigations have found that excess weight is not itself likely to be biologically protective. Rather, the increased mortality seen in patients with lower BMIs may be due to unintentional weight loss caused, for instance, by the presence of a chronic illness, poor nutritional status and function, ongoing systemic inflammation, and/or underlying medical conditions (e.g., cardiovascular/respiratory disease, malignancy).^45,46

A recent study of women with RA enrolled in the Nurses’ Health Study (n=902) and matched comparators without RA (n=7,884) evaluated the impact of weight changes during the early RA period (typically defined as the first 2 years after diagnosis) on subsequent mortality. Baseline weights were obtained 2-4 years before and 2-4 years after RA diagnosis (an index date for non-RA comparators was chosen) in order to capture any weight changes during the peri-RA/peri-index period, including the early RA period. Participants completed questionnaires every 2 years, for up to 40 years of prospective follow-up.

Weight changes during the peri-RA/index period were categorized as stable (±10 pounds), loss, or gain (mild [>10-20], moderate [>20-30], or severe [>30]). Most women in the RA and non-RA cohorts fell in the stable weight category (64.3% and 69.1%, respectively); the majority of these women also fell into the normal BMI categories (54.6% and 58.8%, respectively). Overall, higher subsequent mortality rates during the follow-up period were observed in the RA cohort across all weight-change categories compared with the non-RA cohort. Within the RA cohort, severe unintentional weight loss during the peri-RA period was associated with a more than 3 times increased risk of subsequent mortality compared to stable weight patients with RA and nearly 3 times increased risk compared with stable weight non-RA participants. Similar observations were made in the non-RA comparator cohort, with severe weight loss during the peri-index period associated with a more than 2-fold increased risk of subsequent mortality. While not significant, weight gain in patients with RA was associated with very slightly increased subsequent mortality risk compared with stable weight individuals with RA. A similar pattern was observed in the comparison cohort.⁴⁵

Another study evaluating the impact of low BMI (<20 kg/m2) and weight loss on mortality among patients with RA (N=1,674) found that low BMI was associated with increased risk of death. In addition, the risk of death more than doubled when a rate of BMI loss reached or exceeded 3 kg/m2 per year compared with individuals with no weight loss; this risk was greatest in patients with a low BMI at the time of study exam and a history of obesity.⁴⁶

The takeaway message from both studies was that obesity likely does not serve a biologically protective role in patients with RA; rather, unintentional weight loss, and in particular rapid weight loss, in patients with RA is a worrisome development and signals a need for close monitoring.

Approaches to Weight Loss

Given that excess weight is associated with poorer RA disease activity scores, reduced response to therapy, and decreased likelihood of achieving remission, intentional weight loss is a modifiable and important component of providing comprehensive patient care. One recent study found that modest intentional weight loss (≥5 kg) in overweight/obese patients (BMI ≥25 kg/m2) with RA was associated with 3-fold increased odds of experiencing improved RA disease activity (CDAI improvement of ≥5 points) compared with patients who did not lose weight. Each kilogram of weight loss was associated with a CDAI improvement of 1.15 points.¹⁷

Successful weight loss and subsequent maintenance of that loss involves a complex array of factors and typically requires the work of a multidisciplinary team of providers. Obesity is being increasingly recognized as a multifactorial, heterogenous disease process. As such, specific weight-loss solutions that work well for one individual may not work as well for another, requiring approaches that are tailored to individual weight-loss goals and needs.

In the general population, in-person, high-intensity (ie, ≥14 sessions in 6 months) comprehensive weight-loss interventions that include a reduced calorie diet, increased physical activity, and behavioral strategies provided in individual or group sessions led by a trained interventionist have been found to be the most effective approach to weight-loss treatment.³⁶ Indeed, data have shown that while short-term (3-6 months) weight loss is similar between individuals using diet-only programs compared with combined weight management programs (diet + exercise + behavioral intervention), over the long-term (>12 months), combined programs result in significantly more weight loss. Along the same lines, combined programs have been found to be superior to exercise-only interventions across all time points.⁴⁷

Thus, while providing patient education and support to patients with RA who are pursuing weight loss is key, referral to a comprehensive weight-loss center is sometimes warranted. While the specific structure of individual programs may vary (e.g., all under one roof, a network of various centers partnering together to provide comprehensive services), comprehensive weight-loss centers typically involve numerous team members, including dietitians/nutritionists, health educators, exercise/physical activity coaches, physical/occupational therapists, behaviorists, clinical psychologists/psychiatrists, sleep specialists, and bariatric specialists/surgeons.⁴⁸

Current RA treatment guidelines do not specifically address the management of overweight or obesity.^49,50 Initial weight loss goals vary among individuals and are influenced by the presence and type of weight-related complications, but a weight loss of 5-10% within the first 6 months is typically recommended. This can often be achieved through comprehensive structured lifestyle therapy (dietary changes, increased physical activity, and behavioral interventions/support), with the possibility of obesity pharmacotherapy and bariatric surgery as indicated.^36,48

Dietary Interventions

Reducing caloric intake is a key component of weight-loss interventions. From a weight-loss perspective, no one dietary approach has been found to be better than another. For example, one study evaluating different reduced-calorie macronutrient diets (e.g., varying fat, carbohydrate, and protein levels in numerous combinations) found that while pockets of weight loss success were seen with each dietary approach, no one diet fared better than any other overall. All approaches were associated with greater losses in fat compared with lean mass loss, and changes in body composition, abdominal fat, and hepatic fat were similar between the diets.^51,52

On an individual level, patients with RA may find that a specific diet is more apt to result in sustained weight loss than another; however, no one specific diet has demonstrated benefit for all patients with RA. Consequently, a well-balanced diet that is centered predominately on plant-based foods is generally recommended.

Some studies have shown that there are certain foods that may help control the inflammation of patients with RA, many of which are included in a Mediterranean-style diet that emphasizes the consumption of whole grains, fruits, vegetables, legumes, olive oil, and foods high in omega-3-fatty acids (e.g., tuna, salmon, mackerel). In contrast, meats that have been grilled or fried at high temperatures and foods containing high levels of omega-6-fatty acids (e.g., corn/sunflower/safflower/soybean oils and foods that contain these products) may boost inflammation.⁵³ For individuals with RA, Mediterranean-style diets have been associated with improvements in physical function, increased vitality, and reduced disease activity.^54,55 The Mediterranean diet has also been associated with a reduced risk of CVD and mortality as well as an improved cardiometabolic profile, an issue of concern for many patients with RA.⁴⁸

Exercise

While exercise is a fundamental component of weight loss and health, it can be challenging for patients with RA given the inherent nature of the disease and associated pain, fatigue, impaired joint mobility, and reduced muscle strength.⁵⁶ Exercise regimens that incorporate low-impact aerobic exercise, strength and resistance training, and other activities such as tai chi, yoga, qigong, and whole body vibration have been associated with reduced pain, improved quality of life and functioning, decreased numbers of swollen joints, and lower levels of radiographic damage.^57,58

Unfortunately, recent data indicate that only 27% of patients with RA meet the World Health Organization recommendation for at least 150 minutes of moderate-intensity physical exercise each week. In one study, RA patients demonstrated 20% shorter duration of weekly exercise compared to controls and 40% shorter duration of moderate-to-vigorous activity. In this same study, a higher BMI was significantly related to less physical activity.⁵⁹

It has been recently suggested that individuals with RA engage in moderate-to-high intensity aerobic exercise 3 times weekly in sessions of 30-60 minutes, divided into 3-4 periods of 15-20 minutes per day. Similarly, strengthening exercises to improve joint stability and mobility should be performed for 20-30 minutes, 2-3 times per week.⁵⁸

Behavioral Interventions/Support

Behavioral support constitutes the third element of lifestyle interventions and is focused on supporting and increasing adherence to reduced-calorie meal plans and increased physical activity. There are a wide array of behavioral interventions available including, but not limited to, self-monitoring of diet and activity, education, face-to-face support groups, psychological counseling, and stress reduction.^48,52 Ongoing support for weight loss efforts and patient engagement in the process is key, with higher levels of commitment and contact associated with sustained weight loss over time.⁵²

Many individuals will plateau in their weight loss efforts within 6 months of initiation and may require additional adjustments to their caloric intake and/or physical activity level to lose additional weight or prevent weight rebound.³⁶ Unfortunately, even with the best of efforts, maintaining weight loss with lifestyle interventions over the long-term (>12 months) has proven challenging for many individuals.⁵²

Weight-Loss Medications

For RA patients with overweight (BMI ≥27 with comorbidity) or obesity who have not achieved or maintained weight loss goals with lifestyle therapy alone, the addition of pharmacotherapy can be considered. Adjunctive pharmacotherapy has been associated with greater weight loss and weight-loss maintenance.⁴⁸ In general, the choice of pharmacotherapy should be individualized, with the presence of RA potentially adding a layer of complexity. For instance, long-term use of MTX has been associated with liver enzyme elevations more than two times the upper limit of normal in approximately 13% of patients.⁶⁰ According to professional association recommendations, weight-loss medications should be used with caution in patients with hepatic impairment, so while not a contraindication, a key consideration.⁴⁸

Bariatric Surgery

For many patients, bariatric surgery is a viewed as a ‘last resort’ option, typically considered after lifestyle and pharmacotherapies have not proven effective. An estimated 216,000 individuals in the United States underwent some form of bariatric surgery in 2016.⁶¹

The most common approaches to bariatric surgery include gastric band, Roux-en-Y gastric bypass, vertical sleeve gastrectomy, balloons, and biliopancreatic diversion with a duodenal switch (BPD-DS). Most procedures are performed laparoscopically. In the United States, vertical sleeve gastrectomy accounted for 58.1% of bariatric surgical procedures during 2016, followed by Roux-en-Y (18.7%), gastric band (3.4%), balloons (2.7%), and BPD-DS (0.6%).⁶¹

Vertical sleeve gastrectomy, gastric band, and balloons are considered restrictive procedures wherein food intake is reduced though a reduction in stomach volume and/or delayed gastric emptying. In contrast, Roux-en-Y and BPD-DS are considered restrictive/malabsorptive procedures that create a smaller stomach pouch, which is surgically connected with more distal parts of the small intestine, bypassing proximal portions.⁶² Overall, bariatric surgery has been associated with improved patient outcomes, including weight loss, improvement in weight-related complications, and decreased mortality.⁶² Changes in inflammatory cytokine and adipokine levels have also been reported in patients in general population post-Roux-en-Y surgery, with decreased leptin and CRP and increased adiponectin observed 6 months post-surgery.⁶³

Data evaluating the impact of bariatric surgery in patients in RA is limited. However, Sparks et al conducted a retrospective study of 53 patients with RA and obesity who underwent bariatric surgery (Roux-en-Y gastric bypass [81%], gastric banding [13%], and sleeve gastrectomy [6%]) and found that bariatric surgery was associated with impressive outcomes. All patients were obese prior to surgery, with the following distribution of BMI: BMI 30-34.9 kg/m2 (4%), BMI 35-39.9 kg/m2 (15%), and BMI ≥40 kg/m2 (81%). At baseline, 57% had moderate-to-severe RA disease activity while 26% were in remission.

Twelve months following surgery, patients had collectively lost 70% of excess weight, had significantly reduced RA disease activity and serum inflammatory markers, as well as less RA medication usage compared with baseline. The percentage of patients with moderate-to-high disease activity plummeted from 57% pre-surgery to 6% a year after surgery. Over the same time frame, remission rates pre-and post-surgery jumped from 26% to 68%. In addition, serum inflammatory markers and RA medication usage both dropped post-surgery (see Table 2). While some patients experienced serious adverse events following surgery (reoperation [n=10], serious infection [n=6], intestinal obstruction [n=3], pulmonary embolism [n=1], death [n=1]), it was not possible to determine whether the incidence of these adverse events was different than that observed in the general population due to small sample size.³⁵

While anecdotal concerns have been raised, there is a dearth of data regarding the impact of bariatric procedures on the pharmacokinetics of commonly used oral DMARDs in the treatment of RA, and there are no specific guidelines related to the pre- and post-surgical optimization of DMARD therapy.⁶⁴ Bariatric surgery is associated with anatomical changes that may alter the absorption, distribution, metabolism, and excretion of medications, as well as nutrient and vitamin absorption. Therefore, the management of medications in patients with RA who have undergone bariatric surgery may involve added complexity.⁶⁵ Possible reduced efficacy of oral drugs—in particular enteric, extended-release, or time-release medications—is a core concern.⁶⁴ For example, RA patients undergoing bariatric surgery who receive MTX as part of their treatment should be monitored for decreased efficacy post-surgery.⁶⁵ If inadequate absorption of oral medications is a concern, alternate medications or modes of delivery (e.g.. subcutaneous, liquid) should be considered.64 Furthermore, some RA medications utilize weight-based dosing and may need adjustment as patients lose weight.^66-68 The one clear contraindication is use of nonsteroidal anti-inflammatory drugs, which should avoided if possible as they have been associated with post-operative perforated marginal ulcer in Roux-en-Y gastric bypass patients.^64,69 Lastly, because response to RA medications has been shown to improve with weight loss in some patients, disease activity should be closely monitored and appropriate medication adjustments made.

In order to provide highest-quality care to patients for whom bariatric surgery is a current or near-term consideration, referrals to a bariatric surgery center may be appropriate. These centers undergo a voluntary accreditation process that is focused on patient safety and quality improvement, and they may receive designation from the Surgical Review Corporation as a Bariatric Center of Excellence (see Table 3). The American College of Surgeons also offers an accreditation program (Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program) that is focused on providing high-quality care to patients undergoing bariatric surgery.

Summary

The presence of excess weight in patients with RA is associated with increased disease activity, impaired response to therapy, more pain, and reduced quality of life. More so, individuals with RA who are overweight/obese and have intentionally lost weight demonstrate improvements in disease activity measures, response to RA-related medications, as well as a host of other health benefits. Beyond association with decreased radiographic evidence of joint damage, obesity does not appear to confer additional protective effects. Thus, weight loss in overweight/obese patients should be considered a modifiable factor that can improve not only RA disease activity but other weight-related co-morbidities and health outcomes. It is clear that the management of excess weight in patients with RA is complex; as such, while rheumatology providers are well equipped to provide education and support to patients who would like to lose weight, some patients would benefit from referrals to comprehensive weight-loss centers, which can provide the necessary multidisciplinary education and care required for successful long-term weight loss.