Serious infections hospital admissions and mortality in patients with early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit (2024)

Type of publication:

Conference abstract

Author(s):

Adas M.; Bechman K.; Russell M.; Karafotias I.; Nagra D.; Patel S.; Gallagher S.; Price E.; *Garton M.; Rutherford A.; Cope A.; Norton S.; Galloway J.;

Citation:

Rheumatology. Conference: British Society for Rheumatology Annual Conference, BSR 2024. Liverpool United Kingdom. 63(Supplement 1) (pp i12), 2024. Date of Publication: 01 Apr 2024.

Abstract:

Background/Aims To identify the risk of serious infections (SI) according to initial treatment strategy, using conventional synthetic disease modifying antirheumatic drugs (csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods An observational cohort study design was used. The population included adults in England with a new onset rheumatoid arthritis (RA), fulfilling ACR/EULAR 2010 criteria, between April 2018-March 2021. Outcomes studied were SI, defined by infections requiring hospitalisation (primary admission diagnosis/nosocomial acquisition) or death (SI stated on death certificate), identified using NHS Digital linkage. Patients' characteristics were tabulated by treatment strategies. Hazard ratios (HR) were calculated using single failure Cox proportional-hazards models, with confounders- adjusted models (age, gender, smoking status, comorbidities, social deprivation) and fully-adjusted models including disease factors (seropositivity, DAS28). Individuals were considered at risk from the date of RA diagnosis, and censored at SI event, death, or March 2021 (whichever was earliest). Results 20,060 patients with RA were included. Initial DMARD therapy was known for 19,572 patients, of whom 11,966 were on methotrexate/ MTX based strategies (mono or combo), 5,059 on csDMARD combination strategies (other than MTX) and 2,547 on no DMARD strategy. 15,319 patients were on corticosteroids at baseline. Mean age 59.5 years (+/-15); 63% female; smoking status (20% current; 30% ex-smokers); comorbidities (21% hypertension; 10% diabetes; and 12% lung disease). Rheumatoid Factor/CCP antibodies were positive in 68%. At presentation, median disease scores were 5.1 (interquartile range [IQR]: 4.0-5.9) for DAS28, 1.1 (IQR: 0.6-1.7) for health assessment questionnaire (HAQ) and 24 (IQR: 16.0-33.0) for musculoskeletal health questionnaire (MSKHQ).There were 519 SI admissions and 17 SI deaths, corresponding to incidence rates per 100 person-years for admissions: 3.19 (95% CI: 2.93-3.48) and deaths: 0.10 (95% CI: 0.06-0.16). In fullyadjusted models, increasing age predicted both SI admissions and deaths. Being a smoker, having a comorbidity, higher disease activity (DAS28), symptom burden (MSKHQ) and disability (HAQ) at presentation associated with more SI admissions. For each 1 unit increase in DAS28, the risk of SI increased by 8% (HR 1.08 [95% CI:1.01-1.16]). Seropositivity did not associate with SI. MTX-based strategies 0.75 (95% CI:0.62-0.91) and csDMARD combination therapy 0.70 (95% CI:0.53-0.94) associated with fewer SI admissions compared to no DMARD. In unadjusted models, corticosteroid associated with more SI admissions 1.29 (95% CI:1.10 -1.62); however, in fully-adjusted models this association was no longer statistically significant. csDMARD strategies did not associated with SI deaths in any of the models. Conclusion Patient and disease factors at diagnosis appear to be important predictors of admissions and mortality for serious infections. Infection risk appears to be greatest in those with higher RA disease activity. An important limitation is that NEIAA does not capture data on treatment changes over time and steroid use beyond baseline.

Link to full-text

Trial of atorvastatin for the primary prevention of cardiovascular events in patients with rheumatoid arthritis (TRACE RA): A multicenter, randomized, placebo controlled trial (2019)

Type of publication:
Journal article

Author(s):
Kitas GD, Nightingale P, Armitage J, Sattar N, Belch JJF, Symmons DPM; TRACE RA consortium.

Collaborators (137) Kitas G, Belch J, Symmons D, Williams H, Vasishta S, Storey R, Nightingale P, Bruce I, Durrington P, McInnes I, Nightingale P, Sattar N, Situnayake D, Struthers A, Lowe G, Armitage J, Fox K, Haskard D, Dore C, Bosworth A, Kitas G, Belch J, Symmons D, Williams H, Frenneaux M, Edwards C, Emberson J, Bax D, Cobbe S, Stott D, Sturrock R, Macfarlane P, Klocke R, Pullar T, Knight S, Rowe I, Kumar P, Goodson N, Mulherin D, Brzeski M, Gardiner P, Situnayake D, Walker D, Callaghan R, Allen M, McCarey D, George E, Deighton C, Kirkham B, Teh LS, Luqmani R, Chakravarty K, Nixon J, Richards S, Scott D, Woolf T, Prouse P, Packham J, Davies M, DeLord D, O'Neill T, Pande I, Harvie J, Watts R, Rankin E, Papasavvas G, Emery P, Sinha A, Dasgupta B, Bruce I, Creamer P, Zoma A, Walsh D, Van-Laar J, *Capps N, Cairns A, Marguerie C, Kumar N, Abernethy R, Lillicrap M, Ralston S, Makadsi R, Hopkinson N, Tan S, Akil M, Ahmad Y, Adler M, Bukhari M, Sanders P, Roussou E, Binymin K, Hassan A, Hughes R, O'Reilly D, Sainsbury P, Richmond R, Malgorzata M, Nisar M, McEntergart A, Roy D, Marks J, Batley M, McKenna F, Irani M, Harris H, Smyth A, Tunn E, Young A, Thomas J, Hall F, Marshall T, Rao C, Baburaj K, Dixey J, Gendi N, Birrell F, Chelliah G, Teh LS, Morgan A, Fishman D, Knights S, Coady D, Makadsi R, Smith B, Harrison B, Walker D, Siebert S, Chan A, Putchakayala K, Al-Ansari A, Gough A, Naz S, Kumar N, Pyne D, Mahmud T, Patel Y, Isdale A.

Citation:
Arthritis Rheumatol. 2019 Apr 15. doi: 10.1002/art.40892. [Epub ahead of print]

Abstract:
OBJECTIVE:

Rheumatoid arthritis (RA) is associated with increased cardiovascular event (CVE) risk. The impact of statins in RA is not established. We assessed whether atorvastatin is superior to placebo for the primary prevention of CVE in RA patients.

METHODS:

Randomized, double-blind, placebo-controlled trial designed for 80% power at p<0.05 to detect a 32% CVE risk reduction based on an estimated 1.8% per annum (pa) event rate. Patients aged >50 years or with RA duration >10 years; without clinical atherosclerosis, diabetes, or myopathy; received atorvastatin 40mg daily or matching placebo. Primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, transient ischemic attack, or any arterial revascularization. Secondary/tertiary endpoints included plasma lipids and safety.

RESULTS:

3002 patients (mean age 61 years, 74% female) were followed for a median 2.51 years (IQR 1.90-3.49) [7,827 patient-years] – early termination was due to lower than expected event rate (0.77% pa). Among patients allocated atorvastatin 24/1504 (1.6%) had a primary endpoint, compared with 36/1498 (2.4%) on placebo (hazard ratio 0.66, 95%CI 0.39-1.11, p=0.115); adjusted hazard ratio (0.60, 95%CI 0.32-1.15, p=0.127). At trial end, patients on atorvastatin had 0.77±0.04 mmol/L lower LDL-cholesterol compared to placebo (p<0.0001); CRP (mg/L) was also significantly lower on atorvastatin than placebo (2.59 (0.94-6.08) vs. 3.60 (1.47-7.49) – p<0.0001). CVE risk reduction per mmol/L LDLc reduction was 42% (95%CI -14%-70%). Adverse events in the atorvastatin (298 (19.8%)) and placebo (292 (19.5%)) groups were similar.

CONCLUSION:

Atorvastatin 40mg daily was safe and resulted in significantly greater reduction of LDLc than placebo in patients with RA. The 40% (adjusted) CVE risk reduction is consistent with the Cholesterol Treatment Trialists' Collaboration meta-analysis of statin effects in other populations.

Altmetrics