StemCell Therapy

The 2019 annual meeting of the American College of Rheumatology (ACR) had an abundance of sessions dedicated to the management of rheumatoid arthritis (RA).

Novel TreatmentModalities

A large focus of the novel RA treatment sessions were the Janus kinase (JAK) inhibitors. Multiple abstracts regarding upadacitinib, an oral JAK-1 selective inhibitor, were presented. Josef Smolen, MD, of the University of Vienna in Austria, discussed 48-week results of the SELECT-MONOTHERAPY trial (A Study Comparing Upadacitinib [ABT-494] Monotherapy to Methotrexate [MTX] Monotherapy in Adults With Rheumatoid Arthritis [RA] Who Have an Inadequate Response to MTX; ClinicalTrials.gov Identifier: NCT02706951). For patients continuing upadacitinib 15 mg/d, ACR20, ACR50, and ACR70 response was 87%, 70%, and 46%, respectively; ACR20, ACR50, and ACR70 response for upadacitinib 30 mg/d was 87%, 72%, and 54%, respectively. The most frequent treatment-emergent adverse events were infection, particularly herpes zoster, and elevations in creatine phosphokinase and alanine aminotransferase levels.

Efficacy and safety data on filgotinib, another JAK-1 selective inhibitor, were presented by Bernard Combe, MD, of Montpellier University in France. The FINCH1 (Filgotinib in Combination With Methotrexate in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate; ClinicalTrials.gov Identifier: NCT02889796) study was a phase 3 randomized controlled trial comparing filgotinib 100 mg/d and 200 mg/d with the active comparator, adalimumab 40 mg every 2 weeks, or placebo in addition to a stable dose of methotrexate. The efficacy of filgotinib 200 mg/d was found to be noninferior to adalimumab, achieving a Disease Activity Score in 28 joints/C-reactive protein (DAS28-CRP) score of 3.2 in 60% of participants at week 24.

Updates onPharmacotherapy Safety Data

Several important abstracts regarding pharmacologic safety data in RA were presented at the meeting. Daniel H. Solomon, MD, of Brigham and Womens Hospital in Boston, Massachusetts, presented safety data on methotrexate based on his prespecified secondary analyses of CIRT (Cardiovascular Inflammation Reduction Trial Inflammation Imaging Study; ClinicalTrials.gov Identifier: NCT02576067), which was a randomized controlled trial that included adults with cardiovascular disease and diabetes or metabolic syndrome. Participants were randomly selected to receive low-dose methotrexate (<20 mg/wk) or placebo and were followed for a mean of 27 months. Relative rates of gastrointestinal, infectious, pulmonary, and hematologic adverse events were increased in patients receiving methotrexate compared with participants who were receiving placebo. Notably, there were no differences in the relative rates of malignant, mucocutaneous, neuropsychiatric, musculoskeletal, or renal adverse events.

In addition to upadacitinib as previously mentioned, safetyprofiles of other JAK inhibitors were also presented. Tofacitinib has beenassociated with blood clots in patients who have additional risk factors forthromboembolism. High-dose tofacitinib 10 mg twice daily should not be used inthe treatment of RA. Risk factors for thromboembolism include previouscardiovascular events, cancer, clotting disorders, use of hormonalcontraceptives, and pending major surgery or prolonged immobilization. Datafrom phase 3b/4 trials evaluating tofacitinib 11 mg/d with methotrexate werepresented by Stanley B. Cohen, MD, of the Metroplex Clinical Research Center inDallas, Texas. Importantly, no new safety risks were observed, which wassimilar to that seen with the tofacitinib immediate-release 5 mg twice dailydosage.

A very important and potentially practice-changing updatewas presented by Michael George, MD, of the University of Pennsylvania inPhiladelphia. Dr George analyzed the risk for serious infection associated withlong-term use of glucocorticoids for the treatment of RA. Medicare claims dataon more than 170,000 individuals were used for the analysis. Among older patientswith RA on stable treatment with conventional synthetic and biologic disease-modifyingantirheumatic drugs (DMARDs), prednisone at dosages <5 mg/d weresignificantly associated with increased risk for serious infections. Seriousinfections included urinary infections, pneumonia, bacteremia, and skin or softtissue infections. This study has important management implications forrheumatologists as long-term use of glucocorticoids should be minimized.

Updates onEpidemiology Research in RA

In terms of epidemiology and RA disease trajectory, datafrom the Risk RA Prospective Study were presented by Aase Hensvold of theKarolinska Institute in Stockholm, Sweden. This study followed patients whowere referred to the rheumatology clinic from the primary care setting becauseof positive anti-cyclic citrullinated antibodies but who lacked arthritis uponexamination. A detailed ultrasound evaluation was performed at baseline andfollow-up. Slightly less than half of the enrolled individuals with anti-cycliccitrullinated antibodies developed ultrasound-detectable arthritis at a medianfollow-up time of 11 months. However, participants who had tenosynovitisdetected by ultrasound at baseline were more likely to progress to RA at follow-up.The study highlights the utility of a baseline ultrasound evaluation for thepurpose of prognostication in patients with early or preclinical RA.

Data presented by Elena Myasoedova, MD, PhD, of the MayoClinic College of Medicine and Science in Rochester, Minnesota, explored thechanging epidemiology of RA from a population-based incidence cohort. She foundthat although the incidence of RA has been constant over the past approximately24 years, there has been a decrease in the number of patients with RA withpositive rheumatoid factor and an increase in patients with seronegativedisease. When comparing patients who met the 2010 European League AgainstRheumatism (EULAR)/ACR criteria with those who met the 1987 ACR criteria only,patients in the former group had higher joint counts and were more likely to beever smokers. However, overall the prevalence of smoking declined during the 30-yearstudy period.

Several sessions at the ACR annual meeting featuredcomorbidities in RA. Joshua F. Baker, MD, of the University of Pennsylvania,performed a cross-sectional analysis of diabetes and RA using the VeteransAffairs RA registry. Type 2 diabetes mellitus was present in 26% of patients atenrollment. Multivariable analysis noted that high baseline disease activitywas associated with a greater risk of incident diabetes; prednisone use wascontrolled for in analysis. Interestingly, tumor necrosis factor inhibitor usewas associated with a significantly lower risk for diabetes. This study impliesthat better disease control may lower the risk for subsequent metaboliccomplications such as type 2 diabetes mellitus in patients with RA.

Cardiovascular risk was discussed by Jon T. Giles, MD, ofColumbia University in New York City. Dr Giles presented information about indicatorsof actionable levels of atherosclerosis in patients with RA who traditionallyare labeled as having low or intermediate cardiovascular risk that is based onstandard risk algorithms. Dr Giles found that actionable levels of coronaryartery calcium determined by traditional risk factors such as older age, eversmoking, antihypertensive use, and aspirin use may not necessarily be adequatefor individuals with RA. Particularly, RA disease activity should be anadditional component of the risk algorithm. Using his modified risk algorithm, DrGiles found that a large proportion of patients with RA who were traditionallycategorized as having lower cardiovascular risk may benefit from additionalscreening and prevention strategies. Similarly, Bryant England, MD, of theUniversity of Nebraska, presented data on multimorbidity in RA from acommercial claims database. Compared with baseline enrollment and one-yearfollow-up, the percentage of patients with multimorbidity considerablyincreased for patients with RA compared with those without RA. Therefore, screeningfor and management of chronic conditions in patients with RA is necessary atthe initial visit to prevent the progression of multimorbidity.

The epidemiology of inflammatory arthritis related to immunecheckpoint inhibitors (ICI) that are used in the treatment of cancer waspresented by Tawnie Braaten, MD, of Johns Hopkins School of Medicine in Baltimore,Maryland. Patients with ICI-induced inflammatory arthritis were found to have ratesof seropositivity and persistent disease activity at 3 and 6 months aftercessation of ICIs. Longer duration of ICI use and combination ICIs wereassociated with persistent inflammatory arthritis. Three-quarters of patientsunderwent immunosuppression, which did not appear to affect tumor response.This study is important because the use of ICIs continues to grow in cancertherapy, and patients with resultant inflammatory arthritis will increasinglybe referred to rheumatology practices.

Practice-Changing Updates

Several abstracts related to tapering both conventionalsynthetic and biologic DMARDs were presented at the meeting. In a late-breakingabstract presented by Siri Lillegraven, PhD, of Diakonhjemmet Hospital in Oslo,Norway, patients with RA who were in sustained remission during treatment with conventionalsynthetic DMARDs and who continued therapy tended to have flares less often andwith less radiographic joint progression than patients whose therapy wastapered. The risk of adverse events related to continued therapy on biologicDMARDs and JAK inhibitors was further explored in a meta-analysis presented by DorotheVinson, of Assistance Publique Hospital of Marseille in France. She reportedthat tapering biologic DMARDs and JAK inhibitors did not lead to a decreasedrisk for serious infections, serious adverse events, or malignancy compared withcontinuing treatment.

While the efficacy and safety of pharmacotherapies tend toshape our practice as rheumatologists, Alexis Ogdie-Beatty, MD, of the PerelmanSchool Medicine at the University of Pennsylvania, along with Ben Nowell, PhD,of the Global Healthy Living Foundation in New York City, highlighted thegrowing use of smartphone applications in clinical and research practice. Theirinteresting session titled, Doctor, Should I Get this App? explored therapidly expanding collection of smartphone apps geared toward behavior changes suchas lifestyle improvement with a focus on weight loss, stress, and sleep. Withfurther review by the rheumatology community, these apps may be recommended to patientswith RA to improve certain issues affecting quality of life that may not beamenable to pharmacologic therapies.

Conclusion

There were many interesting and ground-breaking abstractsrelated to RA at this years ACR annual meeting. Data on the safety andefficacy of JAK inhibitors were widely discussed and will continue to be animportant topic of continued research. The decision to taper vs continue conventionalsynthetic and biologic DMARDs in light of important safety data will needfurther investigation. Perhaps with increasing use of mobile technology,monitoring patients between appointments will allow for accelerated research onthe treatment of RA.

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Expert Insights on Rheumatoid Arthritis From the ACR/ARP 2019 Annual Meeting - Rheumatology Advisor

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