Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study.

INTRODUCTION: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. METHODS: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events. RESULTS: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports. CONCLUSION: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile. TRIAL REGISTRATION: NCT04574492.

Efficacy of certolizumab pegol across baseline rheumatoid factor subgroups in patients with rheumatoid arthritis: Post-hoc analysis of clinical trials.

AIM: Certolizumab pegol (CZP), an Fc-free, PEGylated tumor necrosis factor inhibitor (TNFi), has shown rapid and sustained reduction in signs and symptoms of rheumatoid arthritis (RA). Elevated rheumatoid factor (RF) level has been associated with RA disease progression and poorer TNFi response. We assessed the efficacy of CZP in patients with early and established RA across baseline RF levels. METHODS: This post-hoc analysis included data from 6 trials: C-OPERA (NCT01451203), pooled RAPID trials (RAPID-1 [NCT00152386], RAPID-2 [NCT00160602], J-RAPID [NCT00791999], RAPID-C [NCT02151851]), and EXXELERATE (NCT01500278). Patients who received CZP or placebo/comparator with methotrexate (MTX) were categorized by baseline RF quartiles. Efficacy was assessed with Disease Activity Score-28 erythrocyte sedimentation rate (DAS28-ESR). RESULTS: Overall, 316, 1537, and 908 patients were included in C-OPERA, pooled RAPID trials, and EXXELERATE, respectively. Patient demographics and baseline disease characteristics were similar between treatment groups and across RF quartiles. DAS28-ESR low disease activity (LDA) and remission (REM) rates were numerically higher in the CZP + MTX group than PBO + MTX group at weeks 12 and 24, across RF quartiles. LDA and REM rates in the CZP + MTX groups were comparable across RF quartiles at weeks 12 and 24. Mean DAS28-ESR decreased from week 0 to week 24 in the CZP + MTX groups, across RF quartiles. CONCLUSION: CZP showed steady efficacy across baseline RF quartiles in patients with early and established RA, over 24 weeks. CZP treatment may be considered in patients with RA irrespective of baseline RF levels and time from diagnosis.

Long-Term Durability of Certolizumab Pegol in Patients with Rheumatoid Arthritis Over 5 Years: An Analysis of Pooled Clinical Trial Data.

INTRODUCTION: There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5 years between different subgroups of patients with RA. METHODS: Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65 years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10 years). RESULTS: Among 6927 patients, the durability of CZP was 39.7% at 5 years. Patients aged ≥ 65 years had a 33% greater risk of CZP discontinuation than patients 18- < 45 years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1 year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%). CONCLUSIONS: CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1 year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.

Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis: 2-Year Results from the Phase 3 SELECT-PsA 1 Study.

INTRODUCTION: Efficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1. METHODS: Exploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported. RESULTS: Of 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA. CONCLUSIONS: In PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03104400.

Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study.

BACKGROUND: In SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1. METHODS: Patients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised. RESULTS: Consistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups. CONCLUSION: Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

Long-term effectiveness and safety of infliximab and golimumab in ankylosing spondylitis patients from a Canadian prospective observational registry.

BACKGROUND: The objectives of this study were to describe the profile of ankylosing spondylitis (AS) patients treated with either infliximab (IFX) or subcutaneous golimumab (GLM) treatment in Canadian routine care setting along with assessing long-term effectiveness and safety. METHODS: AS patients who were eligible for treatment with IFX or subcutaneous GLM as per their respective Canadian product monographs were enrolled into the BioTRAC registry from 2005 to 2017. The study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in clinical outcomes and acute phase reactants. Safety was evaluated by assessing the incidence of adverse events (AEs) and drug survival rates. RESULTS: A total of 389 IFX- and 421 GLM-treated patients were enrolled. A significant decrease in disease duration at baseline was observed in the IFX cohort, from a median of 8.0 in 2005-2008 to 1.0 years in 2009-2015 (p < 0.001). A reduction in baseline BASFI score (p = 0.011) and proportion of patients in ASDAS very high disease activity (p = 0.004) was also observed over time. Meanwhile, in the GLM cohort, most disease parameters remained similar from 2010 to 2017. Treatment with both agents significantly improved all disease parameters over time with similar efficacy between the two agents. The incidence of AEs and SAEs were 136 and 131 events/100 PYs and 10.5 and 8.45 events/100 PYs for IFX- and GLM-treated patients, respectively. CONCLUSION: Both IFX and GLM treatment in AS significantly reduced disease activity in most outcome measures in a similar fashion and were well tolerated in Canadian routine care. TRIAL REGISTRATION: NCT00741793 .

Incidence and prevalence of giant cell arteritis in Ontario, Canada.

OBJECTIVE: To estimate trends in the incidence and prevalence of GCA over time in Canada. METHODS: We performed a population-based study of Ontario health administrative data using validated case definitions for GCA. Among Ontario residents ≥50 years of age we estimated the annual incidence and prevalence rates between 2000 and 2018. We performed sensitivity analyses using alternative validated case definitions to provide comparative estimates. RESULTS: Between 2000 and 2018 there was a relatively stable incidence over time with 25 new cases per 100 000 people >50 years of age. Age-standardized incidence rates were significantly higher among females than males [31 cases (95% CI: 29, 34) vs 15 cases (95% CI: 13, 18) per 100 000 in 2000]. Trends in age-standardized incidence rates were stable among females but increased among males over time. Incidence rates were highest among those ≥70 years of age. Standardized prevalence rates increased from 125 (95% CI 121, 129) to 235 (95% CI 231, 239) cases per 100 000 from 2000 to 2018. The age-standardized rates among males rose from 76 (95% CI 72, 81) cases in 2000 to 156 (95% CI 151, 161) cases per 100 000 population in 2018. Between 2000 and 2018, the age-standardized rates among females similarly increased over time, from 167 (95% CI 161, 173) to 304 (95% CI 297, 310) cases per 100 000 population. CONCLUSION: The incidence and prevalence of GCA in Ontario is similar to that reported in the USA and northern Europe and considerably higher than that reported for southern Europe and non-European populations.

Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study.

BACKGROUND: The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients' productivity, pain, and fatigue, in Canadian practice. METHODS: FαsT-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients' Assessment of Arthritis Pain (PtAAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). RESULTS: The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. CONCLUSIONS: CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.

Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus.

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Successful treatment of recurrent pleural and pericardial effusions with tocilizumab in a patient with systemic lupus erythematous.

A 22-year-old Caucasian man presented to hospital with pleuritic chest pain. He had had a history of a sun-sensitive rash a year prior. Workup revealed normal cardiac enzymes and chest X-ray. However, electrocardiogram revealed ST elevation and PR depression, and echocardiogram revealed a slight pericardial effusion without other findings. A diagnosis of pericarditis was made. Subsequently, he was found to be positive for antinuclear antibodies (ANAs), as well as antibodies to SSA, SSB and double-stranded DNA; C3 was low, and C4 was undetectable. A diagnosis of systemic lupus erythematosus was made. The patient initially responded to high-dose ibuprofen. One month later, he developed a new pericardial effusion, this time with concomitant massive left-sided pleural effusion, requiring three separate thoracenteses draining a total of 6 L of pleural fluid. The recurrent effusion failed to respond to high-dose corticosteroid treatment. Owing to the severity and rapidity of the recurrence of pleural and pericardial effusion, intravenous tocilizumab was administered. The patient had excellent clinical and radiographic improvement. This case shows that tocilizumab may have a role in the treatment of intractable pleuropericardial effusion and other forms of lupus-associated serositis.

Development and validation of a pediatric IBD knowledge inventory device: the IBD-KID.

OBJECTIVES: Questionnaires exist to assess inflammatory bowel disease (IBD)-related knowledge of adults. Owing to wording and content concerns, these were believed to be inappropriate for use in pediatric patients. The aim of this study was to develop a questionnaire to assess disease-related knowledge of pediatric patients with IBD and their parents. METHODS: Following a formal process of item generation and reduction, the IBD-Knowledge Inventory Device was developed and pilot tested. It was administered to 10- to 17-year-old patients with IBD, and to 1 of each of their parents. To evaluate its discriminatory validity, pediatric residents, nurses, and ward clerks completed the questionnaire. RESULTS: A total of 99 patients (mean 42, Crohn disease 46, age 14(±2) years) and 99 parents completed the IBD-Knowledge Inventory Device. Parent knowledge scores, 15(±4), were higher than those of patients, 11(±4), P < 0.001. Patient and parent knowledge scores were strongly correlated (r = 0.62, P < 0.001). Patient knowledge score was significantly related to disease type (Crohn disease scored higher than ulcerative colitis, P = 0.004) and to perceived knowledge level (P < 0.001) by regression analysis. Similarly, parent knowledge score was significantly related to sex (girls scored higher, P = 0.014), postsecondary education (P < 0.001), and perceived knowledge level (P = 0.002). The questionnaire scores of 23 were 19, 16, and 10, respectively, for residents, nurses, and ward clerks. Both residents and nurses scored significantly higher than ward clerks (P = 0.001 for both). CONCLUSIONS: A valid IBD-related knowledge assessment questionnaire was developed for use in older children and adolescents with IBD and their parents.

Closing the osteoporosis care gap: increased osteoporosis awareness among geriatrics and rehabilitation teams.

BACKGROUND: A care gap exists between recommendations and practice regarding the diagnosis and treatment of osteoporosis in fracture patients. The current study was designed to determine rates and predictors of in-hospital diagnosis and treatment of osteoporosis in patients admitted with fragility hip fractures, and to assess differences in these rates since the outset of the multipronged "Fracture? Think Osteoporosis" (FTOP) Program, which includes education of geriatrics and rehabilitation teams. METHODS: This is a retrospective cohort study conducted with data from two Hamilton, Ontario, university-based tertiary-care hospitals, and represents a follow-up to a previous study conducted 8 years earlier. Data pertaining to all 354 patients, age > or = 50, admitted between March 2003 and April 2004, inclusive, with a diagnosis of fragility hip fracture were evaluated. Twelve patients were excluded leaving 342 patients for analysis, with 75% female, mean age 81.Outcomes included: Primary -- In-hospital diagnosis of osteoporosis and/or initiation of anti-resorptive treatment ("new osteoporosis diagnosis/treatment"). Secondary -- In-hospital mortality, BMD referrals, pre-admission osteoporosis diagnosis and treatment. RESULTS: At admission, 27.8% of patients had a pre-existing diagnosis of osteoporosis and/or were taking anti-resorptive treatment. Among patients with no previous osteoporosis diagnosis/treatment: 35.7% received a new diagnosis of osteoporosis, 21% were initiated on anti-resorptive treatment, and 14.3% received a BMD referral. The greatest predictor of new osteoporosis diagnosis/treatment was transfer to a rehabilitation or geriatrics unit: 79.5% of rehabilitation/geriatrics versus 18.5% of patients receiving only orthopedics care met this outcome (p < 0.001). CONCLUSION: New diagnosis of osteoporosis among patients admitted with hip fracture has improved from 1.8% in the mid 1990's to 35.7%. Initiation of bisphosphonate therapy has likewise improved from 0% to 21%. Although multiple factors have likely contributed, the differential response between rehabilitation/geriatrics versus orthopedics patients suggests that education of the geriatric and rehabilitation teams, including one-on-one and group-based sessions, implemented as part of the FTOP Program, has played a role in this improvement. A significant care gap still exists for patients discharged directly from orthopedic units. The application of targeted inpatient and post-discharge initiatives, such as those that comprise the entire FTOP Program, may be of particular value in this setting.

The relationship between exercise and osteoarthritis in the elderly.

OBJECTIVES: To review within a prescribed evidence-based framework (1) the relationship between intermittent or lifelong physical activity and the subsequent onset or progression of osteoarthritis (OA) in later life and (2) the effect of structured exercise routines on the management of OA in the elderly. DATA SOURCES: A systematic literature search of MEDLINE (1950 to April Week 2, 2008) and EMBASE (1980 to 2008 Week 16) was carried out using the Ovid interface. Relevant mapped terms addressing the identified objectives were combined and exploded according to a defined protocol. STUDY SELECTION: Studies that met relevancy criteria and were of high methodologic quality (prospective cohort studies for the risk factor component and systematic reviews and randomized controlled trials for the therapy component) were extracted and then hand searched for any additional studies. Final inclusion was based on agreement between two independent assessors, according to prescribed criteria. Any studies that were not in the English language, did not address the questions of interest in humans, or did not include a population that had at least a mean age of 55 years at the time of study termination, were excluded. Only land-based regimens were included in the therapy component of the review. DATA EXTRACTION: Pertinent information on subjects, risks, and outcomes (when assessing physical activity as a risk factor for OA in the elderly) and subjects, interventions, and outcomes (when evaluating the application of exercise in the management of OA in older persons) was extracted from the selected studies. DATA SYNTHESIS: Ten studies met entry criteria for examining the relationship between physical activity and the development or progression of OA. Likely because of study variations and differences in the nature, duration and intensities of exercise regimens, no clearcut consensus was apparent on whether or not physical activity was a risk factor for OA. Six scientific reviews and ten single blinded randomized controlled trials were included when evaluating the effect of exercise on OA management. Regardless of wide variability in the included studies, a majority demonstrated that structured exercise programs were effective in the management of older subjects with OA. CONCLUSIONS: : Nuances of study design, differences in age and type of target populations, variability in the intensity, duration, and nature of physical activity in the respective studies, and lack of standardization in the way radiographic data are interpreted are among the factors that prevent consensus regarding the effect of physical activity on later development of OA. Similarly, there is considerable heterogeneity in the studies that assessed exercise in the treatment of OA. Nonetheless, there is substantive evidence in support of the benefits of one or another strength training or aerobic exercise regimen in the management of OA in middle-aged and elderly subjects.

Is regular exercise a friend or foe of the aging immune system? A systematic review.

OBJECTIVE: The purpose of the current review is to synthesize the available evidence from prospective clinical trials that are relevant to the clinical question: "What, if any, are the effects of regular aerobic and/or resistance exercise on the immune system in healthy older adults?" DATA SOURCES: Electronic databases were searched, using terms pertaining to immunology, exercise, and aging. Using the Ovid interface, the following databases were explored: Allied and Complimentary Medicine (AMED) (1985 to 2008), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 2008), all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA, and NHSEED), EMBASE (1980 to 2008), and MEDLINE (1950 to 2008). The MEDLINE database was searched a second time through the PubMed interface. STUDY SELECTION: Prospective controlled clinical trials were selected for review if they investigated the effects of an exercise intervention (minimum 4 weeks in duration) on an immune outcome measure in an older but otherwise healthy population. A total of 19 articles representing 17 trials were identified. DATA EXTRACTION: Quality assessment of the relevant articles was performed using the Jadad et al criteria. Data extraction was performed using a standardized instrument. Data regarding the participants, interventions, and laboratory and clinical immunologic outcomes were synthesized. DATA SYNTHESIS: Available data provide no clear evidence of acute or chronic effects of exercise on lymphocyte or natural killer (NK) cell numbers or phenotype (ie, surface markers)/activity, with 2 exceptions: (1) strength or endurance exercise may cause an acute transient elevation in circulating CD8+ T cells, and (2) regular aerobic exercise appears to enhance immunologic memory in the context of vaccination. The effects of strength training on NK cell activity are unclear. Furthermore, regular aerobic exercise appears to be associated with a reduction in chronic inflammation. Finally, no prospective controlled trials have clearly documented clinical immunologic benefits of regular exercise, which may well relate to underpowering of these studies. CONCLUSIONS: Overall, in healthy older adults, regular, particularly aerobic, exercise appears to be a friend of the immune system, helping to offset diminished adaptive responses and chronic inflammation. The possibility exists that particularly strenuous exercise may cause acute immunologic changes, such as diminished NK cell activity, which could predispose to infection in certain individuals. However, given the possible benefits of regular exercise on the immune system and the many definite benefits on other systems, the evidence presented here should not dissuade practitioners from suggesting regular exercise to otherwise healthy older adults.