ACR clinical year in review

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Some of the most influential papers and research in rheumatology from the last year were presented in this ACR highlight.

Here are the some of the most influential papers and research in rheumatology from the last year.

Presented by Dr Karen Costenbader, the review covered research and papers on trials of new therapies, the evolving story of JAK inhibitors, improving clinical care, disparities in rheumatology and combatting covid-19.

Trials of new therapies/indications

Avacopan for the Treatment of ANCA-Associated Vasculitis – NEJM 2021, 18 February

In a study of 331 patients, half were randomised to receive avacopan and half to receive prednisone as adjunct therapy. At 52 weeks, avocopan was superior to prednisone taper with around 66% in sustained remission (vs 55% for PRD). Avacopan was approved by the FDA for AAV in October 2021.

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial – Lancet 2021, 7 May

Patients taking voclosporin vs placebo as add-on to standard of care (MMF and corticosteroids) had a clinically and statistically superior complete renal response rate (41% vs 23%). Voclosporin was FDA approved in January 2021.

Evolving story of JAKi

Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study – Ann Rheum Dis 2021, 13 July

Patients with inadequate response or intolerance to two or more NSAIDs were randomised to receive 5mg tofacitinib bid vs placebo. At week 16, 56% of tofacitinib patients achieved primary endpoint of ASAS20, vs 29% of placebo group.

FDA-mandated post-approval study of tofacitinib in RA patients

The primary outcomes were MACE, CV death, non-fatal MI, non-fatal-stroke and malignancies (excluding non-melanoma skin cancer). Non-inferiority to anti-TNF was not met for MACE or malignancy. There is no published paper as yet.

Improving clinical care

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial – JAMA 2021, 11 March

RA patients in remission who had their csDMARD dose halved experienced more disease flares than those remaining on a stable csDMARD dose (25% vs 6%).

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial – Ann Rheum Dis 2021, 12 October

In a comparison of a tight-control/treat-to-target strategy vs usual care in axSpA patients, difference in primary outcome (ASAS-HI improved by 30% or more) was non-significant, though there was a health economic benefit.

Stepped Exercise Program for Patients With Knee Osteoarthritis: A Randomized Controlled Trial – Ann Int Med 2021, March

Patients who received a stepped exercise program for knee osteoarthritis (internet exercise program -> coaching calls -> in-person physical therapy) had a WOMAC score 6.8 points lower than controls (arthritis education) at 9-months follow-up – a “modest” improvement.

Disparities in rheumatology

Socioeconomic Disparities in Functional Status in a National Sample of Patients With Rheumatoid Arthritis – JAMA Network Open 2021, 4 August

Patients from lower SES levels had worse functional status and faster declines in functioning over time.

An algorithmic approach to reducing unexplained pain disparities in underserved populations – Nature Medicine 2021, 13 January

An AI system trained using x-rays and patients’ own assessments of their condition outperformed doctors in diagnosing osteoarthritis patients, particularly for minority and lower SES patients who tend to be subject to physician bias. This could help lead to better treatment options.

Combatting covid-19

Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes – NEJM 2021, 1 July

In this US study, children and adolescents with covid-associated MIS-C given initial treatment with intravenous immune globulin (IVIg) plus glucocorticoids (GC) had lower risk of cardiovascular dysfunction and initiation of vasopressors and adjunctive therapy than IVIg alone.

Treatment of Multisystem Inflammatory Syndrome in Children – NEJM 2021, 1 July

In an international study with results apparently conflicting with those above, researchers found no difference in outcomes among IVIg alone, IVIg + GC, or GC alone, although IVIg + GC had lower risk of escalation of immunomodulatory treatment.

Reasons for discrepancies could include different populations, different time frames, different criteria for initiating treatment and different covid variants.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry – Ann Rheum Dis 2021, 17 June

In a physician-reported registry of adults with rheumatic disease and covid, 10.5% died. Factors related to death were age, male sex, hypertension and CV disease, chronic lung disease and >10mg/day prednisolone, as well as moderate-to-high disease activity and certain medications (rituximab, sulfasalazine and immunosuppressants).

Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2: A Prospective Cohort Study – Ann Int Med 2021, 31 August

Double-dosed patients with chronic inflammatory disease taking GC and B-cell depleting therapy had lower anti-spike and neutralising antibody responses.

More from ACR21…

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