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 Treatment Modalities
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 on Pharmacotherapy Safety Data
Several important abstracts regarding pharmacologic safety data in RA were presented at the meeting. Daniel H. Solomon, MD, of Brigham and Women’s 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, safety profiles of other JAK inhibitors were also presented. Tofacitinib has been associated with blood clots in patients who have additional risk factors for thromboembolism. High-dose tofacitinib 10 mg twice daily should not be used in the treatment of RA. Risk factors for thromboembolism include previous cardiovascular events, cancer, clotting disorders, use of hormonal contraceptives, and pending major surgery or prolonged immobilization. Data from phase 3b/4 trials evaluating tofacitinib 11 mg/d with methotrexate were presented by Stanley B. Cohen, MD, of the Metroplex Clinical Research Center in Dallas, Texas. Importantly, no new safety risks were observed, which was similar to that seen with the tofacitinib immediate-release 5 mg twice daily dosage.
A very important and potentially practice-changing update was presented by Michael George, MD, of the University of Pennsylvania in Philadelphia. Dr George analyzed the risk for serious infection associated with long-term use of glucocorticoids for the treatment of RA. Medicare claims data on more than 170,000 individuals were used for the analysis. Among older patients with RA on stable treatment with conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs), prednisone at dosages <5 mg/d were significantly associated with increased risk for serious infections. Serious infections included urinary infections, pneumonia, bacteremia, and skin or soft tissue infections. This study has important management implications for rheumatologists as long-term use of glucocorticoids should be minimized.
Updates on Epidemiology Research in RA
In terms of epidemiology and RA disease trajectory, data from the Risk RA Prospective Study were presented by Aase Hensvold of the Karolinska Institute in Stockholm, Sweden. This study followed patients who were referred to the rheumatology clinic from the primary care setting because of positive anti-cyclic citrullinated antibodies but who lacked arthritis upon examination. A detailed ultrasound evaluation was performed at baseline and follow-up. Slightly less than half of the enrolled individuals with anti-cyclic citrullinated antibodies developed ultrasound-detectable arthritis at a median follow-up time of 11 months. However, participants who had tenosynovitis detected 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 the purpose of prognostication in patients with early or preclinical RA.
Data presented by Elena Myasoedova, MD, PhD, of the Mayo Clinic College of Medicine and Science in Rochester, Minnesota, explored the changing epidemiology of RA from a population-based incidence cohort. She found that although the incidence of RA has been constant over the past approximately 24 years, there has been a decrease in the number of patients with RA with positive rheumatoid factor and an increase in patients with seronegative disease. When comparing patients who met the 2010 European League Against Rheumatism (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 be ever smokers. However, overall the prevalence of smoking declined during the 30-year study period.
Several sessions at the ACR annual meeting featured comorbidities in RA. Joshua F. Baker, MD, of the University of Pennsylvania, performed a cross-sectional analysis of diabetes and RA using the Veterans Affairs RA registry. Type 2 diabetes mellitus was present in 26% of patients at enrollment. Multivariable analysis noted that high baseline disease activity was associated with a greater risk of incident diabetes; prednisone use was controlled for in analysis. Interestingly, tumor necrosis factor inhibitor use was associated with a significantly lower risk for diabetes. This study implies that better disease control may lower the risk for subsequent metabolic complications such as type 2 diabetes mellitus in patients with RA.
Cardiovascular risk was discussed by Jon T. Giles, MD, of Columbia University in New York City. Dr Giles presented information about indicators of actionable levels of atherosclerosis in patients with RA who traditionally are labeled as having low or intermediate cardiovascular risk that is based on standard risk algorithms. Dr Giles found that actionable levels of coronary artery calcium determined by traditional risk factors such as older age, ever smoking, antihypertensive use, and aspirin use may not necessarily be adequate for individuals with RA. Particularly, RA disease activity should be an additional component of the risk algorithm. Using his modified risk algorithm, Dr Giles found that a large proportion of patients with RA who were traditionally categorized as having lower cardiovascular risk may benefit from additional screening and prevention strategies. Similarly, Bryant England, MD, of the University of Nebraska, presented data on multimorbidity in RA from a commercial claims database. Compared with baseline enrollment and one-year follow-up, the percentage of patients with multimorbidity considerably increased for patients with RA compared with those without RA. Therefore, screening for and management of chronic conditions in patients with RA is necessary at the initial visit to prevent the progression of multimorbidity.
The epidemiology of inflammatory arthritis related to immune checkpoint inhibitors (ICI) that are used in the treatment of cancer was presented by Tawnie Braaten, MD, of Johns Hopkins School of Medicine in Baltimore, Maryland. Patients with ICI-induced inflammatory arthritis were found to have rates of seropositivity and persistent disease activity at 3 and 6 months after cessation of ICIs. Longer duration of ICI use and combination ICIs were associated with persistent inflammatory arthritis. Three-quarters of patients underwent immunosuppression, which did not appear to affect tumor response. This study is important because the use of ICIs continues to grow in cancer therapy, and patients with resultant inflammatory arthritis will increasingly be referred to rheumatology practices.
Several abstracts related to tapering both conventional synthetic and biologic DMARDs were presented at the meeting. In a late-breaking abstract presented by Siri Lillegraven, PhD, of Diakonhjemmet Hospital in Oslo, Norway, patients with RA who were in sustained remission during treatment with conventional synthetic DMARDs and who continued therapy tended to have flares less often and with less radiographic joint progression than patients whose therapy was tapered. The risk of adverse events related to continued therapy on biologic DMARDs and JAK inhibitors was further explored in a meta-analysis presented by Dorothée Vinson, of Assistance Publique Hospital of Marseille in France. She reported that tapering biologic DMARDs and JAK inhibitors did not lead to a decreased risk for serious infections, serious adverse events, or malignancy compared with continuing treatment.
While the efficacy and safety of pharmacotherapies tend to shape our practice as rheumatologists, Alexis Ogdie-Beatty, MD, of the Perelman School Medicine at the University of Pennsylvania, along with Ben Nowell, PhD, of the Global Healthy Living Foundation in New York City, highlighted the growing use of smartphone applications in clinical and research practice. Their interesting session titled, “Doctor, Should I Get this App?” explored the rapidly expanding collection of smartphone apps geared toward behavior changes such as lifestyle improvement with a focus on weight loss, stress, and sleep. With further review by the rheumatology community, these apps may be recommended to patients with RA to improve certain issues affecting quality of life that may not be amenable to pharmacologic therapies.
There were many interesting and ground-breaking abstracts related to RA at this year’s ACR annual meeting. Data on the safety and efficacy of JAK inhibitors were widely discussed and will continue to be an important topic of continued research. The decision to taper vs continue conventional synthetic and biologic DMARDs in light of important safety data will need further investigation. Perhaps with increasing use of mobile technology, monitoring patients between appointments will allow for accelerated research on the treatment of RA.