Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy.

OBJECTIVES: This post hoc analysis assessed speed, magnitude and maintenance of pain improvement in patients with early rheumatoid arthritis (RA) receiving baricitinib, baricitinib and methotrexate (MTX), or MTX over 1 year. Cumulative pain and quality of life benefits were also assessed. METHODS: Randomised, double-blind, phase 3 study RA-BEGIN (NCT01711359) compared baricitinib 4 mg (N=159), baricitinib 4 mg +MTX (N=215) and MTX (N=210) in patients with RA who had no or limited prior disease-modifying antirheumatic drug treatment. Pain was assessed on a 0-100 mm Visual Analogue Scale (VAS). Proportion of patients with ≥30%, ≥50% and ≥70% pain improvement from baseline; ≤20 mm and ≤10 mm on the pain VAS; and time to achieve pain improvement thresholds were assessed over 52 weeks, as were Patient Global Assessment (PtGA) and 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS) outcomes. RESULTS: Baricitinib monotherapy or combination with MTX provides greater (least square mean changes (LSM) from baseline -40 mm and -43 mm, respectively) and more rapid (median 12 and 8 weeks to ≥70% improvement, respectively) pain relief than MTX alone (LSM -31 mm, median 20 weeks to ≥70% improvement) over 52 weeks. Baricitinib, alone or combination, provides 9-10 additional weeks of limited to no pain, similar gain in achievable wellness measured through PtGA, and 5-7 additional weeks with change in SF-36 PCS ≥5 vs MTX over 1 year. CONCLUSIONS: Patients treated with baricitinib reported significantly greater and more rapid pain relief, more weeks with limited to no pain, and clinically meaningful improvements in physical health than patients treated with MTX alone over 1 year.

Call for action: incorporating wellness practices into a holistic management plan for rheumatoid arthritis-going beyond treat to target.

This expert opinion article explores the strategy of adopting a holistic approach to the management of rheumatoid arthritis (RA) by incorporating the wellness practices of exercise, optimised sleep, optimised nutrition, mindfulness, social connectedness and positive emotions into the management plan. The aim is to attain optimal health for each patient beyond that achievable by limiting disease management to pharmacological treatment to attain the lowest achievable composite scores of disease activity, as recommended with the current treat-to-target approach, and addressing the recent recognition of pain control as a key patient-reported outcome. Incorporating wellness practices into a busy clinical setting requires creativity and customisation based on the individual practice setting and the individual needs of each patient. Such practices can help people living with RA to achieve optimum wellness through the introduction of measures-according to individual need-designed to improve the aspects of life most impacted for that person, thereby complementing treat-to-target and pain control strategies with pharmacological agents. Clinicians must consider wellness practices in addition to treat-to-target pharmacological agents for the holistic management of people with RA.

Prevalence of Renal Impairment in a US Commercially Insured Rheumatoid Arthritis Population: A Retrospective Analysis.

INTRODUCTION: Global prevalence estimates for chronic kidney disease (CKD) in rheumatoid arthritis (RA) vary. This study assessed real-world prevalence estimates of renal impairment, based on estimated glomerular filtration rate (eGFR), among commercially insured patients with RA in the United States (US). METHODS: In this retrospective cohort study, we used administrative claims data from the HealthCore Integrated Research Database (HIRD®) between January 2013 and December 2018. Adult patients with ≥ 2 claims for RA and ≥ 2 serum creatinine (SCr) measurements ≥ 90 days apart on or after the index date were included. eGFR was calculated per the Modification of Diet in Renal Disease equation. Prevalence of eGFR-based renal impairment was estimated for the overall RA population and for two subgroups: patients on advanced therapies (biologic disease-modifying antirheumatic drugs/tofacitinib) and patients stratified based on health plan types. RESULTS: Among 128,062 patients with ≥ 2 RA claims, 42,173 had qualifying SCr measurements, 16,197 were on advanced RA therapies, and 4911 had Medicare Advantage or Supplemental plus Part D coverage. For the overall population and the subgroup on advanced therapies, mild renal impairment was observed in 52% and 51%, moderate renal impairment in 9% and 7%, and severe renal impairment in 0.5% and 0.3% of patients, respectively. Moderate and severe renal impairment was more prevalent in the Medicare Advantage/Supplemental plus Part D population compared to the commercial coverage population. CONCLUSIONS: Approximately 7-10% of commercially insured adult patients in the US with RA had moderate or severe renal impairment. Assessment of renal function is an important consideration for safe treatment.

Efficacy of Long-Term Treatment with Once-Daily Baricitinib 2 mg in Patients with Active Rheumatoid Arthritis: Post Hoc Analysis of Two 24-Week, Phase III, Randomized, Controlled Studies and One Long-Term Extension Study.

INTRODUCTION: To evaluate long-term efficacy of once-daily baricitinib 2 mg in patients with active rheumatoid arthritis who had an inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) or biologic DMARDs (bDMARD). METHODS: Data from patients treated with baricitinib 2 mg daily in two 24-week, phase III studies, RA-BUILD (csDMARD-IR; NCT01721057) and RA-BEACON (bDMARD-IR; NCT01721044), and one long-term extension study (RA-BEYOND; NCT01885078), were analyzed (120 weeks). The main outcomes were achievement of low-disease activity (LDA; Simple Disease Activity Index [SDAI] ≤ 11), clinical remission (SDAI ≤ 3.3), Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ 0.5 and improvement from baseline of ≥ 0.22, and safety. Analysis populations included (1) all patients and (2) never-rescued patients. Completer and non-responder imputation (NRI) analyses were conducted on each population. RESULTS: In RA-BUILD, 684 were randomized (229 to baricitinib 2 mg, 180 of whom completed RA-BUILD and entered RA-BEYOND). In RA-BEACON, 527 were randomized (174 to baricitinib 2 mg, 117 of whom completed RA-BEACON and entered RA-BEYOND). In RA-BUILD-BEYOND, 85.1% (63/74, completer) and 27.5% (63/229, NRI) of csDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 40.5% (30/74, completer) and 13.1% (30/229, NRI) were in SDAI remission; 62.2% (46/74, completer) and 20.1% (46/229, NRI) had HAQ-DI ≤ 0.5 and 81.1% (60/74, completer); and 26.2% (60/229, NRI) achieved ≥ 0.22 change from baseline at week 120. In RA-BEACON-BEYOND, 86.5% (32/37, completer) and 18.4% (32/174, NRI) of bDMARD-IR patients treated with baricitinib 2 mg achieved SDAI LDA; 24.3% (9/37, completer) and 5.2% (9/174, NRI) were in SDAI remission; 50.0% (19/38, completer) and 10.9% (19/174, NRI) had HAQ-DI ≤ 0.5; and 73.7% (28/38, completer) and 16.1% (28/174, NRI) achieved ≥ 0.22 change from baseline at week 120. Rates of adverse events of special interest were consistent with previous reports. CONCLUSIONS: Long-term treatment with baricitinib 2 mg demonstrated efficacy for up to 120 weeks and was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01721057, NCT01721044, and NCT01885078.

Frequency of Prescription Claims for Drugs that May Interact with Janus Kinase Inhibitors Among Patients with Rheumatoid Arthritis in the US.

INTRODUCTION: This study describes the frequency of prescription claims for drugs that may interact with Janus kinase (JAK) inhibitors among adult patients with rheumatoid arthritis (RA) in a large US claims database. METHODS: This observational, retrospective, cross-sectional study of the IBM® MarketScan® Research Commercial and the Medicare Supplemental Database included adults (≥ 18 years) with ≥ 2 outpatient claims 30 or more days apart or ≥ 1 inpatient visit claim with an RA diagnosis between January 1, 2013 and March 31, 2017 (the index period). During the study period, from January 1, 2013 to March 31, 2018, strong organic anion transporter (OAT3) inhibitors, strong cytochrome P450 (CYP) 3A4 inhibitors, and moderate or strong CYP3A4 inhibitors in combination with strong CYP2C19 inhibitors, were identified as drugs with potential for drug-drug interactions (DDIs) with JAK inhibitors approved for RA treatment in the US. Descriptive statistics were conducted. RESULTS: A total of 152,853 patients met eligibility criteria. Approximately 76% were women and the median age was 57 years. Of these patients, < 0.1% had a claim for a strong OAT3 inhibitor, and 1% had claims for the combination of a strong CYP3A4 and strong CYP2C19 inhibitor; 3% of patients had a claim for a strong CYP3A4 inhibitor and almost 10% had claims for both a moderate CYP3A4 and a strong CYP2C19 inhibitor. CONCLUSIONS: Up to 10% of RA patients have been prescribed a drug with a potential JAK interaction. Rheumatologists should consider potential DDIs when managing patients with RA.

The Jak/STAT pathway: A focus on pain in rheumatoid arthritis.

Pain is a manifestation of rheumatoid arthritis (RA) that is mediated by inflammatory and non-inflammatory mechanisms and negatively affects quality of life. Recent findings from a Phase 3 clinical trial showed that patients with RA who were treated with a Janus kinase 1 (Jak1) and Janus kinase 2 (Jak2) inhibitor achieved significantly greater improvements in pain than those treated with a tumor necrosis factor blocker; both treatments resulted in similar changes in standard clinical measures and markers of inflammation. These findings suggest that Jak1 and Jak2 inhibition may relieve pain in RA caused by inflammatory and non-inflammatory mechanisms and are consistent with the overarching involvement of the Jak-signal transducer and activator of transcription (Jak/STAT) pathway in mediating the action, expression, and regulation of a multitude of pro- and anti-inflammatory cytokines. In this review, we provide an overview of pain in RA, the underlying importance of cytokines regulated directly or indirectly by the Jak/STAT pathway, and therapeutic targeting of the Jak/STAT pathway in RA. As highlighted herein, multiple cytokines directly or indirectly regulated by the Jak/STAT pathway play important roles in mediating various mechanisms underlying pain in RA. Having a better understanding of these mechanisms may help clinicians make treatment decisions that optimize the control of inflammation and pain.

Defining Pain That Does Not Interfere With Activities Among Rheumatoid Arthritis Patients.

OBJECTIVE: The objectives of this study were to: 1) characterize the distribution of noninterfering pain (defined as the pain intensity level at which individuals can function without interference) across different aspects of life among patients with rheumatoid arthritis (RA), and 2) identify clinical characteristics associated with differing levels of noninterfering pain. METHODS: Patients with RA in FORWARD, The National Databank for Rheumatic Diseases completed 8 items from the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference item bank that asked about interference with activities. If subjects reported pain interference, they were asked, "At what level would pain no longer interfere with this activity?" on a scale of 0 to 10. Subjects were also asked, "At what level of pain would you be able to do everything you want to do?" Multiple linear regression analyses examined associations between clinical characteristics and noninterfering pain. RESULTS: A total of 3,949 patients with RA completed the questionnaires. Pain interference was most common for daily activities and least common for ability to concentrate. The mean ± SD level at which pain no longer interfered with activities ranged from 2.7 ± 2.1 for ability to fall/stay asleep to 3.1 ± 2.0 for social activities. Overall, the mean ± SD threshold for noninterfering pain was 2.8 ± 1.9. The mean ± SD level of pain at which patients could do everything they wanted to do was 2.3 ± 1.9. More severe pain intensity was associated with higher noninterfering pain. CONCLUSION: The mean pain level that did not interfere with activities was 3. High pain intensity was associated with high self-reported noninterfering pain.

Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM.

Patients with rheumatoid arthritis (RA) may experience residual pain and functional impairment despite good control of disease activity. This study compared improvements in pain and physical function in patients with well-controlled RA after 24 weeks' treatment with baricitinib, adalimumab or placebo in the 52-week RA-BEAM phase III study. Adults with active RA and inadequate response to methotrexate received baricitinib 4 mg once daily, adalimumab 40 mg every two weeks or placebo, with background methotrexate. Patients (N = 1010) were categorised as in remission, in remission or low disease activity, or not in remission or low disease activity at week 24. For patients in remission or low disease activity (n = 310), improvements in mean pain and physical function scores at week 24 were significantly greater with baricitinib than placebo (p < 0.001 and p < 0.01, respectively) and adalimumab (p < 0.05 for both). For both outcomes, differences between adalimumab and placebo were not significant. The proportions of patients in remission or low disease activity with minimal or no pain and with normalised physical function were numerically greater with baricitinib than placebo. Baricitinib 4 mg once daily provided enhanced improvement in pain and physical function in patients with well-controlled RA, suggesting it may produce effects beyond immunomodulation.

Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotrexate: Results from the RA-BEAM Trial.

The purpose of the study was to assess the proportion of patients who achieve pain relief thresholds, the time needed to reach the thresholds, and the relationship between pain and inflammation among patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate in RA-BEAM (NCT0170358). A randomized, double-blind trial was conducted, comparing baricitinib (N = 487), adalimumab (N = 330), and placebo (N = 488) plus methotrexate. Pain was evaluated by patient's assessment on a 0-100 mm visual analog scale (VAS). The following were assessed through a 24-week placebo-controlled period: the proportion of patients who achieved ≥30%, ≥50%, and ≥70% pain relief, the time to achieve these pain relief thresholds, remaining pain (VAS ≤ 10 mm, ≤20 mm, or ≤40 mm), and the relationship between inflammation markers and pain relief. Baricitinib-treated patients were more likely (p < 0.05) to achieve ≥30%, ≥50%, and ≥70% pain relief than placebo- and adalimumab-treated patients, as early as Week 1 vs. placebo and at Week 4 vs. adalimumab. A greater proportion of baricitinib-treated patients achieved ≤20 mm or ≤40 mm remaining pain vs. placebo- and adalimumab-treated patients. Baricitinib-treated patients tended to demonstrate consistent pain relief independent of levels of inflammation control. In RA patients with an inadequate response to methotrexate, baricitinib provided greater and more rapid pain relief than adalimumab and placebo. Analyses suggest the relationship between inflammation and pain may be different for baricitinib and adalimumab treatments.

Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials.

OBJECTIVE: To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms. METHODS: Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores). RESULTS: Patients achieving remission/low disease activity (LDA) at Week 24 had larger/significant improvements from baseline in pain, MJS, disability, fatigue, and physical and emotional quality of life versus patients with high/moderate disease activity. Some patients achieving remission and LDA, reported residual pain (pain VAS >10 mm): 20.8-39.3% and 48.7-70.0% (overall study populations), 16.0-34.5% and 47.1-62.0% (Japanese patients). Residual MJS and fatigue were also reported. CONCLUSION: Remission/LDA were associated with improvements in PROs in overall and Japanese patient populations; however, some patients achieving remission had residual symptoms, including pain.

Changing Smart Pump Vendors: Lessons Learned.

Smart infusion pump technology is a mainstay in health care, and the integration and use of those pumps is crucial for patient safety. An institution purchasing smart infusion pumps has the ability to trial the various vendors before purchase, however literature that documents a conversion from one pump to another is lacking. This article describes the conversion from one smart infusion pump platform to another at a government institution and a large multisite facility. The differences in 2 smart infusion pumps are described as well as lessons learned following the conversion in both organizations.