Revisiting the JOQUER trial: stratification of primary Sjögren’s syndrome and the clinical and interferon response to hydroxychloroquine

Alexis Collins, Dennis Lendrem, James Wason, Jessica Tarn, Nadia Howard-Tripp, Iris Bodewes, Marjan A. Versnel, Jacques Eric Gottenberg, Raphaele Seror, Xavier Mariette, Wan Fai Ng*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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To re-analyse the clinical outcomes and interferon (IFN) activity data from the JOQUER trial, a phase III trial investigating hydroxychloroquine (HCQ) in patients with primary Sjögren’s syndrome (pSS), after stratifying patients into putative pathobiological subgroups utilizing the Newcastle Sjögren’s Stratification Tool (NSST) based on patient-reported symptoms of dryness, pain, fatigue, anxiety and depression. 107 patients were assigned to one of four subgroups using NSST at baseline—the high symptom burden (HSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and low symptom burden (LSB). Endpoints were re-analysed after stratification, testing for treatment differences within subgroups and adjusting for baseline differences using a repeated measures covariate model. The HSB subgroup (n = 32) showed a relative improvement in ESSPRI of 1.49 points (95% CI 0.54–2.43; p = 0.002) within 12 weeks in patients taking HCQ compared to placebo, with no further changes after 24 weeks. For the LSB subgroup (n = 14), the ESSPRI worsened in the placebo but not the HCQ arm after 12 weeks (mean difference 1.44, 95% CI 0.05–2.83, p = 0.042). Neither the HSB nor the LSB patients showed significant changes in IFN activity at 24 weeks. There were no significant differences in ESSPRI in the PDF (n = 39) and DDF (n = 22) patients taking HCQ. However, significant reductions in overall IFN score at 24 weeks were seen in both PDF (difference at 24 weeks; 6.41, 95% CI, 2.48–10.34, p = 0.002) and DDF (difference at 24 weeks; 7.23, 95% CI, 1.85–12.6, p = 0.009) without improvement in ESSPRI. Although the JOQUER trial reported no overall benefit from HCQ in pSS patients, stratification suggests that both HSB and LSB subgroups may respond to HCQ. However, these patients may benefit through mechanisms other than the reduction of IFN activities.

Original languageEnglish
Pages (from-to)1593-1600
Number of pages8
JournalRheumatology International
Issue number9
Publication statusPublished - 24 Jun 2021

Bibliographical note

Funding Information:
The Medical Research Council funded the work leading to the development of the Newcastle Sjögren’s Stratification Tool (NSST). The Foundation for Research in Rheumatology (FOREUM) funded the work for the re-analysis of the clinical trials and included funding for JRT and DL. The work was also funded by the Innovative Medicines Initiative 2 Joint Undertaking (JU) (NECESSITY grant agreement No 806975) receiving support from the European Union’s Horizon 2020 research and innovation program and EFPIA. DL’s work has also been funded by NIHR Newcastle Biomedical Research Centre. AFC’s work was funded by the Academic Foundation Programme at the Northern Foundation School. ILB was funded by the Dutch Arthritis Society (14–3–404). The JOQUER trial was sponsored by Assistance Publique-Hôpitaux de Paris (AP-HP) with a grant from the French Ministry of Research (Programme Hospitalier de Recherche Clinique National 2007 P070125).

Publisher Copyright:
© 2021, The Author(s).


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