Evaluating the real-world effectiveness of belimumab in patients with SLE using SLE-related laboratory values and rheumatoid arthritis-derived disease activity measures: RAPID3, swollen joint count and tender joint count.

OBJECTIVE: To investigate the real-world impact of intravenous belimumab treatment among patients with SLE using rheumatoid arthritis-derived disease activity measures and SLE-related laboratory values. METHODS: This retrospective cohort study used US electronic medical record data from the United Rheumatology Normalised Integrated Community Evidence (UR-NICE) database. Adult patients with SLE who initiated intravenous belimumab between 1 January 2012 and 3 December 2019 (index), had 12 months of pre-index and 24 months of post-index clinical activity, and had ≥6 infusions of belimumab during the 24 months post-index were included. The primary outcome measure was time to first improvement of minimally important difference (MID) for Routine Assessment of Patient Index Data 3 (RAPID3), Patient Pain Index (PPI), swollen joint count, tender joint count (TJC), complement C3 and C4 and anti-double-stranded DNA antibodies during the on-treatment follow-up period of up to 24 months. The secondary outcome measure evaluated the trajectories of these outcome measures for up to 24 months of belimumab treatment. RESULTS: Of 495 patients included, between 21.0% and 52.1% had ≥1 record for each of the disease activity measures or laboratory values in the pre-index and post-index periods and were included in analyses for that measure. The proportion of patients achieving MID for each measure increased rapidly within 3 months, with continued gradual improvement throughout the remaining on-treatment period, up to 24 months. After 6 months, 52.3% and 55.3% of patients had achieved MID in RAPID3 and PPI, respectively. Outcome measure trajectories indicated improved disease activity with belimumab treatment, particularly in RAPID3, TJC and laboratory values. CONCLUSIONS: In this real-world effectiveness study, belimumab therapy for SLE resulted in clinically meaningful improvements in rheumatoid arthritis-derived disease activity measures within 3 months of treatment, with patients who remained on belimumab therapy experiencing improvement even up to 24 months of observation.

Steroid-sparing effect of belimumab: results from a retrospective observational study of real-world data.

OBJECTIVE: Comparison of oral corticosteroid (OCS) use in patients with SLE in a US rheumatology network pre- and post-belimumab initiation. METHODS: This retrospective cohort study (GSK Study 214140) used data from the Patient-Important Outcomes Data Repository (PIONEER)-Rheumatology database. Eligible adults with SLE initiated belimumab between 1 January 2012 and 30 June 2021, and had available data for >180 days pre- and >360 days post-belimumab initiation. The index was the date of belimumab initiation. Changes in OCS use were measured by: proportion of patients receiving OCS; mean total OCS dose/patient; mean total number of OCS days supplied/patient; mean daily OCS dose for days supplied/patient; the proportion of patients with OCS doses of ≤5 mg/day and ≤7.5 mg/day for days supplied. These changes were assessed between period (P)1 (6 months pre-index) and P2 (first 6 months post-index) and P3 (second 6 months post-index) in patients with OCS use in P1 who persisted with belimumab at each assessed period. RESULTS: Overall, 608 patients received belimumab for 180 days (full analysis set (FAS)) and 492 for 360 days. Most patients were female (92.8%); 70.4% had moderate SLE. In P1, 56.3% of FAS patients and 54.5% of patients who persisted with belimumab for 360 days received OCS.Among patients receiving OCS in P1, significantly fewer patients received OCS in P2 (78.4%) and P3 (64.9%) vs P1 (100.0%). Significant reductions from P1 were observed in P2 and P3 in the mean total OCS dose/patient, the mean OCS daily dose for days supplied and the proportions of patients with OCS dose of ≤5 mg/day and ≤7.5 mg/day, and the mean total OCS days supplied/patient in P3 only. CONCLUSIONS: This analysis showed significant reductions in OCS dose and use in patients with SLE who persisted with belimumab, providing more real-world evidence for belimumab's steroid-sparing effect.

Tracking of Systemic Lupus Erythematosus (SLE) Longitudinally Using Biosensor and Patient-Reported Data: A Report on the Fully Decentralized Mobile Study to Measure and Predict Lupus Disease Activity Using Digital Signals-The OASIS Study.

(1) Objective: Systemic lupus erythematosus (SLE) is a complex disease involving immune dysregulation, episodic flares, and poor quality of life (QOL). For a decentralized digital study of SLE patients, machine learning was used to assess patient-reported outcomes (PROs), QOL, and biometric data for predicting possible disease flares. (2) Methods: Participants were recruited from the LupusCorner online community. Adults self-reporting an SLE diagnosis were consented and given a mobile application to record patient profile (PP), PRO, and QOL metrics, and enlisted participants received smartwatches for digital biometric monitoring. The resulting data were profiled using feature selection and classification algorithms. (3) Results: 550 participants completed digital surveys, 144 (26%) agreed to wear smartwatches, and medical records (MRs) were obtained for 68. Mining of PP, PRO, QOL, and biometric data yielded a 26-feature model for classifying participants according to MR-identified disease flare risk. ROC curves significantly distinguished true from false positives (ten-fold cross-validation: p < 0.00023; five-fold: p < 0.00022). A 25-feature Bayesian model enabled time-variant prediction of participant-reported possible flares (P(true) > 0.85, p < 0.001; P(nonflare) > 0.83, p < 0.0001). (4) Conclusions: Regular profiling of patient well-being and biometric activity may support proactive screening for circumstances warranting clinical assessment.

Healthcare Resource Utilization and Associated Costs in Patients With Systemic Lupus Erythematosus Diagnosed With Lupus Nephritis.

BACKGROUND: Lupus nephritis (LN) is among the most severe organ manifestations of systemic lupus erythematosus (SLE), affecting between 31% and 48% of patients, usually within five years of SLE diagnosis. SLE without LN is associated with a high economic burden on the healthcare system, and although data are limited, several studies have shown that SLE with LN could increase this burden.  Aim: We aimed to compare the economic burden of LN versus SLE without LN among patients managed in routine clinical practices in the USA and describe the clinical course of these patients. MATERIALS AND METHODS: This was a retrospective observational study of patients with commercial or Medicare Advantage health insurance. It included 2310 patients with LN and 2310 matched patients who had SLE without LN; each patient was followed for 12 months after diagnosis (the patient's index date). Outcome measures included healthcare resource utilization (HCRU), direct healthcare costs, and SLE clinical manifestations.  Results: In all healthcare settings, the mean (SD) use of all-cause healthcare resources was significantly higher in the LN versus SLE without LN cohort, including the mean number of ambulatory visits (53.9 (55.1) vs 33.0 (26.0)), emergency room visits (2.9 (7.9) vs 1.6 (3.3)), inpatient stays (0.9 (1.5) vs 0.3 (0.8)), and pharmacy fills (65.0 (48.3) vs 51.2 (42.6)) (all p<0.001). Total all-cause costs per patient in the LN cohort were also significantly higher compared with the SLE without LN cohort ($50,975 (86,281) vs $26,262 (52,720), p<0.001), including costs for inpatient stays and outpatient visits. Clinically, a significantly higher proportion of patients with LN experienced moderate or severe SLE flares compared with the SLE without LN cohort (p<0.001), which may explain the difference in HCRU and healthcare costs. CONCLUSION: All-cause HCRU and costs were higher for patients with LN than for matched patients with SLE without LN, highlighting the economic burden associated with LN.

Real-World Clinical Outcomes in Belimumab-Treated US African American and Hispanic Patients with Systemic Lupus Erythematosus: A Retrospective, Observational Study.

INTRODUCTION: This analysis aims to describe real-world clinical outcomes in US African American and Hispanic patients with systemic lupus erythematosus (SLE) receiving belimumab. METHODS: In this post hoc analysis of OBSErve US (GSK Study 117,295) data, patients received intravenous belimumab (10 mg/kg) over 24 months. Outcomes assessed every 6 months after belimumab initiation (index) included: physician-assessed overall clinical response (worse, no improvement, < 20%, 20-49%, 50-79%, ≥ 80% improvement), physician-assessed disease severity (mild, moderate, severe), oral corticosteroid (OCS) use and healthcare resource utilization (HCRU). RESULTS: Of 501 patients enrolled, 123 and 88 were African American and Hispanic respectively; 69 (56.1%) and 43 (48.8%) were receiving belimumab at 24 months. Of those, 88.4%/95.3% (African American/Hispanic) were female; mean (standard deviation [SD]) age was 41.6 (12.5)/42.2 (10.5) years. Within 6 months post-index, 91.3%/90.7% of patients still receiving belimumab had a ≥ 20% physician-assessed clinical improvement. Among 24 months completers, proportions of patients with severe SLE fell from 34.8%/25.6% at index to 2.9%/4.7% at Month 6 and 2.9%/0% at Month 24. The proportion of patients receiving OCS and mean (SD) daily OCS dose also decreased, from 82.6%/81.4% and 19.7 (12.8)/18.8 (10.0) mg/day at index to 50.7%/34.9% and 3.1 (3.2)/1.6 (2.4) mg/day at Month 24. Fewer patients were hospitalized or required ancillary care services at 18-24 months post-index versus 6 months pre-index. CONCLUSION: Belimumab treatment for up to 2 years improved clinical outcomes, disease severity, mean OCS dose and HCRU in US African American and Hispanic patients with SLE, providing real-world evidence for enduring belimumab effectiveness in populations that are markedly impacted by SLE.

A 5-Year Retrospective, Observational Study Assessing Rheumatoid Arthritis Disease Outcome Measures to Characterize Systemic Lupus Erythematosus Burden in the USA.

INTRODUCTION: We evaluated the use of rheumatoid arthritis (RA) disease measures in patients with systemic lupus erythematosus (SLE) in a US community-based rheumatology physician network over 5 years. METHODS: This retrospective, observational cohort study (GSK Study 213818) of patients with SLE utilized electronic medical records (01 January 2010-31 December 2019) from the United Rheumatology Normalized Integrated Community Evidence database. The index was the date of first SLE diagnosis recorded in the database; the observation period was 5 years post-index. RA disease measures evaluated were: Pain Index, Multi-Dimensional Health Assessment Questionnaire (MD-HAQ), Patient Global Assessment (PtGA), Physician Global Assessment (PGA), Swollen Joint Count (SJC), Tender Joint Count (TJC), Routine Assessment of Patient Index Data 3 (RAPID3), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score 28 (DAS-28). The number of patients with measures utilized, the score on each measure, and proportion of patients per disease activity category were assessed. RESULTS: Overall, 5990 patients with SLE were included. The most frequently used measures were Pain Index, SJC, TJC, MD-HAQ, PtGA, RAPID3, and PGA (cumulative use over Years 1-5: 23.9-71.3%). For all measures, frequency of use was lowest in Year 1, followed by a general increase from Year 1 to Year 5. Scores remained relatively stable for most measures, and the proportion of patients in remission or with low/moderate disease activity per RAPID3 increased. CONCLUSION: RA disease measure utilization in SLE was generally infrequent but increased over time. Pain Index and MD-HAQ were the most commonly applied cumulatively across 5 years of follow-up. The rationale for the increased use of these measures in SLE over time requires further exploration. In the absence of a clinically applicable SLE-specific measure, the use of RA measures, for example in conjunction with SLE measures, may provide an alternative approach for measuring disease activity, representing an opportunity to improve patient outcomes.

Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related Disease.

CASE: A 50-year-old African American male presented with abdominal pain and significant weight loss. On physical examination, he had parotid and submandibular gland enlargement associated with right eye proptosis. Computed tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph nodes, and ascending aortic aneurysm. Laboratory results were remarkable for elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed chronic sclerosing sialadenitis, with a large subset of inflammatory cells positively staining for IgG4. The histology of the paravertebral mass demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related disease (IgG4-RD). Steroid therapy initially yielded improvement; however, after steroids were stopped, there was disease recurrence. Prednisone was restarted, and the plan was to start him on rituximab. Interestingly, the patient's brother also had IgG4-RD. CONCLUSION: IgG4-RD can present as a paravertebral mass which is usually responsive to steroids; however, recurrent and resistant disease can be seen for which steroid-sparing agents such as rituximab should be considered. In addition, to the best of our knowledge, this is the first reported case of IgG4-RD in two family members presenting as a paravertebral mass, highlighting an exciting area for more research in the future.

Embolic Stroke as the Initial Manifestation of Systemic Lupus Erythematosus.

We present a case of a 21-year-old African-American female with no significant medical history, who presented to the emergency department with a one-week history of blurry and double vision. Ophthalmology evaluation revealed bilateral retinal artery occlusion. Further workup with imaging of the brain was consistent with an ischemic stroke. Hereditary hypercoagulable workup was unremarkable and initial testing for antiphospholipid syndrome was positive. She underwent transesophageal echocardiogram (TEE), which showed severe mitral regurgitation and thickening of mitral valve leaflets consistent with Libman-Sacks endocarditis. Autoimmune workup was positive for IF-ANA, anti-RNP, and anti-Smith antibody. She fulfilled 4/11 of the ACR criteria and met 5 of the SLICC (Systemic Lupus International Collaborating Clinics) criteria for lupus (nonscaring alopecia, thrombocytopenia, positive ANA, and positive anti-Smith and positive anti-phospholipid antibodies). This case highlights the importance of early recognition of underlying connective tissue diseases and timely management of these diseases in young patients with no previous manifestations of diseases.

A challenging twist in pulmonary renal syndrome.

Case. We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. A 75-year-old African American woman with history of high blood pressure on hydralazine for 3 years presented with acute onset of shortness of breath and hemoptysis. Lab workup revealed a severe normocytic anemia and a serum creatinine of 5.09 mg/dL (baseline 0.9). Bronchoscopy demonstrated active pulmonary hemorrhage. A urine sample revealed red cell casts and a renal biopsy demonstrated pauci-immune, focally necrotizing glomerulonephritis with small crescents consistent with possible anti-neutrophil cytoplasmic antibody-positive renal vasculitis. Serologies showed high-titer MPO-ANCA and high-titer anti-histone antibodies. She was treated with intravenous steroids and subsequently with immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Conclusion. Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present as a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titer of anti-myeloperoxidase anti-neutrophil cytoplasmic antibody with multiantigenicity, positive anti-histone antibodies, and the lack of immunoglobulin and complement deposition. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed.

Managing osteoarthritic knee pain.

Osteoarthritis is one of the most common forms of arthritis seen in primary care practice. Pain associated with this condition is the chief complaint of most patients, prompting them to seek medical attention. Pain can originate from the synovial membrane, joint capsule, periarticular muscles and ligaments, and periosteum and subchondral bone, among other sources. Although osteoarthritis is traditionally thought of as a noninflammatory type of arthritis, inflammatory mechanisms can be present. Therefore, management of osteoarthritic pain involves both nonpharmacologic and pharmacologic modes of therapy. Nonpharmacologic approaches include osteopathic manipulative treatment, physical therapy, exercise, use of assistive devices, and weight reduction. Pharmacologic options may be topical, intra-articular, or oral in route of administration and include acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids. Patients often benefit from combinations of therapeutic modalities. Although pain relief is a chief motivator for patients with osteoarthritis to seek medical attention, a secondary benefit of successful treatment is slowing the decrease in patients' quality of life.

Association of baseline disease and patient characteristics with response to etoricoxib and indomethacin for acute gout.

BACKGROUND AND OBJECTIVE: Disease history and clinical features can influence treatment response in patients with acute gout. The purpose of this pooled subgroup analysis was to assess the association of baseline disease and patient characteristics with response to treatment in acute gout using data from two identical studies. METHODS: Patients > or = 18 years of age with onset of acute gout within 48 h associated with moderate, severe, or extreme pain involving less than four joints were eligible for inclusion in the primary studies, and were randomized to etoricoxib 120 mg once daily (N = 178) or indomethacin 50 mg three times daily (N = 161). The primary and secondary efficacy endpoints were analyzed using an analysis of covariance model to detect potential differential treatment responses across several subgroups: joint involvement (mono-articular vs. oligo-articular), baseline pain severity (moderate vs. severe), concomitant allopurinol and/or colchicine use (users vs. nonusers), age (< 45, 45-55, and > 55 years), gender, and race (white or other). RESULTS: Overall, etoricoxib and indomethacin demonstrated comparable efficacy across all subgroups. Compared with patients with oligo-articular disease, those with mono-articular disease had significantly greater improvements in patient assessment of pain, patient global assessment of response to therapy (PGART), investigator global assessment of response to therapy (IGART), and study joint tenderness (p < 0.001 for all). Greater improvements were seen in patient assessment of pain (p < 0.001) and study joint tenderness (p < 0.05) for severe/extreme baseline pain compared with moderate baseline pain. Concomitant use of colchicine and/or allopurinol was associated with significantly worse IGART (p < 0.05). CONCLUSIONS: This pooled subgroup analysis demonstrated significantly greater response of acute gout to either etoricoxib or indomethacin among those with monoarticular disease, severe/extreme baseline pain, and non-use of colchicine and/or allopurinol. These results should be interpreted in the context of a pooled subgroup analysis with a limited sample size, and with the understanding that associations identified in such analyses do not define causation. Despite limitations, the results provide insights into the types of patients more likely to respond better to anti-inflammatory medication, and reiterate the importance of earlier effective control of the disease.

Rofecoxib 12.5 mg, rofecoxib 25 mg, and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies.

OBJECTIVE: To compare the efficacy of rofecoxib and celecoxib for the treatment of knee or hip OA over 6 weeks. METHODS: Two similarly designed, multicenter, randomized, double-blind, placebo-controlled studies. Patients were randomly assigned 3:3:3:1 in Study 1 to once daily (QD) rofecoxib 12.5 mg (N = 456), rofecoxib 25 mg (N = 459), celecoxib 200 mg (N = 456), or placebo (N = 150) and 3:3:1 in Study 2 to QD rofecoxib 25 mg (N = 471), celecoxib 200 mg (N = 460), or placebo (N = 151). There was no rofecoxib 12.5 mg arm in Study 2. The primary outcome measure of both studies was pain at night over 6 weeks for rofecoxib 25 mg vs. celecoxib 200 mg. Efficacy comparisons with rofecoxib 12.5 mg in Study 1 were included as pre-specified study objectives but not as pre-specified study hypotheses. Secondary endpoints included Patient Global Assessment of Response to Therapy (PGART) over 6 weeks and over 1 week. Safety was evaluated through the assessment of spontaneously reported adverse experiences (AEs), evaluation of vital signs, and laboratory data reported by investigators and patients. RESULTS: For the primary endpoint, reduction in pain at night over 6 weeks in Study 1 was not significantly different between active treatments; in Study 2 rofecoxib 25 mg significantly (p = 0.023) reduced pain at night compared with celecoxib 200 mg over 6 weeks. For the secondary endpoints, in both studies, significantly (p < 0.05) more patients treated with rofecoxib 25 mg than celecoxib 200 mg had a good or excellent PGART over 6 weeks, and over the first week (p < 0.01). In both studies, there were no significant differences between active medications in the incidence of reported overall, serious, or drug-related AEs. The reported AE rates with the active treatments were generally similar to those with placebo in the two studies. CONCLUSIONS: Rofecoxib 25 mg was significantly better than celecoxib 200 mg in relieving night pain at 6 weeks in one study; this was not confirmed in the accompanying study.

Management of osteoarthritic knee pain.

Osteoarthritis (OA) is one of the most common forms of arthritis seen in primary care practice. The pain associated with this condition is the chief complaint of most patients, prompting them to seek medical attention. Pain can originate from the synovial membrane, joint capsule, periarticular muscles and ligaments, and periosteum and subchondral bone, among other sources. Osteoarthritis is traditionally thought of as a noninflammatory type of arthritis; however, inflammatory mechanisms can be present. Therefore, the management of osteoarthritic pain involves nonpharmacologic modes of therapy as well as pharmacologic agents. Nonpharmacologic therapeutic modalities include osteopathic manipulative treatment, physical therapy, exercise, use of assistive devices, and weight reduction. Pharmacologic options, categorized as topical, intra-articular, or oral, include acetaminophen, nonsteroidal anti-inflammatory agents, and cyclooxygenase type 2 inhibitors. Patients often benefit from use of a combination of these therapeutic modalities. Although pain relief is a chief motivator for patients with OA to seek medical attention, a secondary benefit of successful treatment is to delay the decreased quality of life associated with osteoarthritic pain.

Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of etoricoxib and indomethacin in the treatment of patients with acute gout. METHODS: A randomized, double-blind, active-comparator study was conducted at 42 sites. A total of 189 men and women (> or =18 years of age) who were experiencing an acute attack (< or =48 hours) of clinically diagnosed gout were treated for 8 days with etoricoxib, 120 mg/day (n = 103), or indomethacin, 50 mg 3 times a day (n = 86). The primary efficacy end point was the patient's assessment of pain in the study joint (0-4-point Likert scale) over days 2-5. Safety was assessed by adverse experiences (AEs) occurring during the trial. RESULTS: Etoricoxib demonstrated clinical efficacy comparable to that of indomethacin in terms of the patient's assessment of pain in the study joint. The difference in the mean change from baseline over days 2-5 was -0.08 (95% confidence interval -0.29, 0.13) (P = 0.46), which fell within the prespecified comparability bounds of -0.5 to 0.5. Secondary end points over the 8-day study, including the onset of efficacy, reduction in signs of inflammation, and patient's and investigator's global assessments of response to therapy, confirmed the comparable efficacy of the two treatments. The etoricoxib-treated patients had a numerically lower incidence of AEs (43.7%) than did the indomethacin-treated patients (57.0%) and a significantly lower incidence of drug-related AEs (16.5% versus 37.2%; P < 0.05). CONCLUSION: Etoricoxib at a dosage of 120 mg once daily was confirmed to be an effective treatment for acute gout. Etoricoxib was comparable in efficacy to indomethacin at a dosage of 50 mg 3 times daily, and it was generally safe and well tolerated.

An analysis of osteoporosis-related hip fractures using hospital discharge data.

The purpose of this study was to assess whether physicians in practice inadequately diagnose osteoporosis in a high-risk population of postmenopausal women who have sustained hip fractures. Using the Texas Hospital Discharge Data-Public Use Data File (PUDF) provided through the Texas Health Care Information Council, the authors conducted a review of all postmenopausal women older than 55 years with fractured hips discharged from Texas hospitals during 1999. A total of 13,628 patients meeting these criteria were found using the PUDF. In their diagnoses, physicians for 2233 (16.3%) of these 13,628 women also specified the code for osteoporosis (P < .001) from the ninth revision of the International Classification of Diseases. It is estimated that between 40% and 50% of postmenopausal women have osteoporosis. Therefore, women with fragility fractures form an even more at-risk subset of the population--so much so that one would expect a majority of these women to carry diagnoses of osteoporosis. The age distribution in each group was comparable, implying that receiving a coded diagnosis for osteoporosis was not related to the age of the patient when she was admitted to the hospital. Further, when data was analyzed by race or ethnicity, percentages for each group (ie, diagnosed with hip fracture only versus diagnosed with hip fracture and osteoporosis) were comparable. In conclusion, physicians practicing in Texas during calendar year 1999 inadequately diagnosed osteoporosis in a high-risk population of postmenopausal women who were admitted to hospitals with fractured hips. Future analysis of subsequent annual databases will identify whether continuing medical education efforts cause physicians to diagnosis osteoporosis in this high-risk population more frequently.