Never Too Late: Late-Breaking Abstracts Create Excitement

EULAR 2022 (VIRTUAL)—The pace of scientific progress in research medicine is incredible and seems to only accelerate with time. Thus, the 2022 Congress of the European Alliance of Associations for Rheumatology (EULAR) session on late-breaking abstracts fittingly captured the excitement and timeliness of a number of research projects that have just recently been completed and analyzed, thereby providing insights into a wide array of topics.

Deucravacitinib for SLE

Eric Morand, MD, PhD, professor and head of the School of Clinical Sciences at Monash Health and head of the Monash Health Rheumatology Unit, Melbourne, Australia, provided the first presentation on a study investigating the efficacy and safety of deucravacitinib in patients with active systemic lupus erythematosus (SLE). Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 inhibitor.

In a 48-week, randomized, double-blind, placebo-controlled phase 2 trial, 363 patients with SLE on standard background medications were randomized to receive deucravacitinib 3 mg twice per day (BID), 6 mg BID, 12 mg BID or placebo. Of note, oral corticosteroid tapering to 7.5 mg/day was required from weeks 8–20.

The primary end point in this study was the proportion of patients achieving an SLE Responder Index (4) (SRI[4]) response at week 32. The authors found a significantly greater proportion of patients in the group receiving 3 mg of deucravacitinib twice daily (58.2% vs. placebo 34.4%; P=0.0006) and the group receiving 6 mg of deucravacitinib twice daily group (49.5% vs. placebo 34.4%; P=0.021) achieved an SRI(4) response than patients receiving a placebo. The SRI(4) response was sustained across all deucravacitinib groups up to 48 weeks.¹

The rates of adverse events were similar in the deucravacitinib and placebo groups, and the most common adverse events with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache and urinary tract infections.

The authors concluded that deucravacitinib shows promise as a novel therapy for SLE and warrants a phase 3 trial.

Bimekizumab for Psoriatic Arthritis

Next, Iain McInnes, MD, PhD, professor of experimental medicine, director of Research Institute (Immunology), Muirhead Chair of Medicine and director of Institute School of Medicine, Dentistry and Nursing, University of Glasgow, Scotland, discussed a study on the efficacy and safety of bimekizumab in patients with psoriatic arthritis naive to biologic disease-modifying anti-rheumatic drugs (bDMARDs).

Bimekizumab is a monoclonal anti-IgG1 antibody that selectively inhibits interleukin (IL) 17F and IL-17A. Patients in this study were randomized to 160 mg of bimekizumab via subcutaneous injection every four weeks, 40 mg of adalimumab via subcutaneous injection every two weeks or placebo.

With bimekizumab treatment, the authors noted improvements in joint and skin outcomes, as well as in the composite outcome of minimal disease activity, in the patients in the trial.² Bimekizumab met the primary (i.e., ACR50 at week 15) and ranked secondary end points (i.e., 1: Health Assessment Questionnaire-Disability Index change from baseline; 2: PASI90; 3: Short Form 36 physical component summary change from baseline; 4: minimal disease activity; and 5: van der Heijde-modified total Sharp score change from baseline). Bimekizumab resulted in inhibition of structural progression in the overall population of patients, as well as in patients with risk factors for progression, such as elevated high sensitivity C-reactive protein (hsCRP) and/or ≥1 bone erosion at baseline.

Dr. McInnes noted the dual inhibition of IL-17F and IL-17A seems to provide efficacy across multiple domains of psoriatic arthritis, perhaps presenting a model for treatment of this disease.

Baricitinib for Juvenile Idiopathic Arthritis

In the third abstract presentation, Athimalaipet Ramanan, FRCPCH, FRCP, professor, consultant pediatric rheumatologist at Bristol Royal Hospital for Children and Royal National Hospital for Rheumatic Diseases, Bath, England, discussed a phase 3 trial of baricitinib in the treatment of patients with juvenile idiopathic arthritis (JIA).

As many rheumatologists are aware, baricitinib is a Janus kinase 1/2 selective inhibitor approved for the treatment of rheumatoid arthritis. The multi-center, double-blind, efficacy and safety study was divided into three periods: a two-week pharmacokinetic/safety assessment, a 12-week open-label lead-in and an up-to-week 32 double-blind withdrawal period.³

In this study, time of flare was significantly shorter for patients receiving a placebo than for those receiving baricitinib (hazard ratio 0.24 [95% CI 0.13,0.45]; P<0.001). The proportion of patients with a flare was significantly lower for baricitinib vs. placebo (14 [17.1%] vs. 41 [50.6%]; P<0.001). At week 12 in the group of patients receiving baricitinib, 76.3% achieved JIA-ACR30, 63.5% achieved JIA-ACR50, 46.1% achieved JIA-ACR70, and 20.1% achieved JIA-ACR90. When considering the known safety profile of baricitinib in adults with rheumatoid arthritis, no new safety findings of concern were found.

The patients enrolled in this trial were individuals aged 2 to <18 years with extended oligo- or polyarticular JIA, enthesitis-related arthritis or juvenile psoriatic arthritis and an inadequate response to one or more conventional synthetic DMARDs (csDMARDs) and/or bDMARDs. The authors noted that baricitinib may be a potential treatment for such patients.

Methotrexate & AstraZeneca COVID-19 Vaccine

In the fourth presentation of the session, Anu Sreekanth, MD, Sree Sudheendra Medical Mission, Kochi, India, discussed the effects of withdrawing methotrexate after both doses vs. after only the second dose of the ChAdOx1 nCoV-19 vaccine (from AstraZeneca) among patients with autoimmune inflammatory arthritis.

In this study, the authors recruited patients with rheumatoid arthritis or psoriatic arthritis on a stable dose of methotrexate without prior COVID-19 infection. Unvaccinated patients were randomized to either hold or continue methotrexate for two weeks after each dose of the vaccine. For patients who had continued methotrexate during their first dose of the vaccine, these individuals were randomized to hold or continue methotrexate for two weeks after the second dose of the vaccine.

The authors found that holding methotrexate after both doses or only after the second vaccine dose yielded higher anti-receptor binding domain antibody titers than continuing methotrexate. In addition, holding methotrexate after only the second dose appeared to be non-inferior to holding methotrexate after both doses of the vaccine, with a lower risk of flare.⁴

Sarilumab for Relapsing Polymyalgia Rheumatica

In the penultimate presentation, Bhaskar Dasgupta, MBBS, MD, FRCP, consultant rheumatologist, The London Clinic, England, discussed the efficacy of sarilumab in patients with relapsing polymyalgia rheumatica (PMR). Sarilumab is a fully human anti-IL-6Rα monoclonal antibody.

In this study, patients with PMR who had flared on ≥7.5 mg/day prednisone or equivalent were randomized to 52 weeks of treatment with 200 mg of sarilumab every two weeks plus a 14-week glucocorticoid tapering regimen, or placebo every two weeks plus a 52-week glucocorticoid tapering regimen.

The primary end point in the study was the proportion of patients achieving sustained remission at week 52—as defined by remission at week 12, absence of disease flare, C-reactive protein normalization from weeks 12–52 and adherence to the protocolized glucocorticoid taper from weeks 12–52. Sustained remission rate was significantly higher in the sarilumab arm vs. the comparator arm (28.3% vs. 10.3%; P=0.0193), and patients in the sarilumab arm were 44% less likely to have a flare after achieving clinical remission compared with patients in the comparator arm (16.7% vs. 29.3%; HR 0.56; 95% CI 0.35–0.90; P=0.0158).

Dr. Dasgupta noted the study was terminated early because of prolonged recruitment timelines during the COVID-19 pandemic. However, using the data that was collected, the authors concluded that sarilumab with a 14-week glucocorticoid taper showed significant efficacy compared with the comparator arm in glucocorticoid-refractory PMR patients, including clinically meaningful improvement in quality of life.⁵ This could represent a notable additional therapy in this often difficult-to-treat condition.

Orelabrutinib for SLE

In the final presentation, Zhanguo Li, MD, PhD, professor, chief of the Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, discussed orelabrutinib in the treatment of SLE. The medication is an irreversible inhibitor of Bruton’s tyrosine kinase, and in this study SRI(4) and SLE Disease Activity Index (SLEDAI) scores appeared to improve in patients receiving all three dose levels of orelabrutinib (i.e., 50, 80 and 100 mg by mouth daily) compared with placebo.⁶ This study presents orelabrutinib as a potentially efficacious agent in the treatment of SLE.

In Sum

In coming years, many potential therapeutics in rheumatology may be said to have found their footholds in these initial oral presentations.

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Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.

References

1. Morand E, Pike M, Merrill JT, et al. Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: A phase 2, randomized, double-blind, placebo-controlled study [abstract LB0004]. Ann Rheum Dis. 2022;81(suppl 1):209.
2. Mcinnes I, Coates L, Landewé RBM, et al. Bimekizumab in bdmard-naive patients with psoriatic arthritis: 24-week efficacy & safety from BE OPTIMAL, a phase 3, multicentre, randomised, placebo-controlled, active reference study [abstract LB0001]. Ann Rheum Dis. 2022;81(suppl 1):206–207.
3. Ramanan A, Quartier P, Okamoto N, et al. Baricitinib in juvenile idiopathic arthritis: A phase 3, double-blind, placebo-controlled, withdrawal, efficacy and safety study [abstract LB0002]. Ann Rheum Dis. 2022;81(suppl 1):207–208.
4. Sreekanth A, Skaria T, Joseph S, et al. Withdrawing methotrexate after both versus only second dose of the ChAdOx1 nCoV-19 vaccine in patients with autoimmune inflammatory arthritis: two independent randomized controlled trials (MIVAC I and II) [abstract LB0003]. Ann Rheum Dis. 2022;81(suppl 1):208–209.
5. Dasgupta B, Unizony S, Warrington KJ, et al. Sarilumab in patients with relapsing polymyalgia rheumatica: A Phase 3, multicenter, randomized, double blind, placebo controlled trial (SAPHYR) [abstract LB0006]. Ann Rheum Dis. 2022;81(suppl 1):210–211.
6. Li R, Zhu X, Liu S, et al. Orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), for the treatment of systemic lupus erythematosus (SLE): results of a randomized, double-blind, placebo-controlled, phase IB/IIA dose-finding study [abstract LB0005]. Ann Rheum Dis. 2022;81(suppl 1):210.