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Clinical Trial
. 2021 Sep;41(9):1593-1600.
doi: 10.1007/s00296-021-04927-y. Epub 2021 Jun 24.

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

Alexis Collins  1 , Dennis Lendrem  1   2 , James Wason  3 , Jessica Tarn  1 , Nadia Howard-Tripp  1 , Iris Bodewes  4 , Marjan A Versnel  4 , Jacques-Eric Gottenberg  5 , Raphaele Seror  6   7 , Xavier Mariette  6   7 , Wan-Fai Ng  8   9
Affiliations
Clinical Trial

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

Alexis Collins et al. Rheumatol Int. 2021 Sep.

Abstract

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.

Keywords: Hydroxychloroquine; Interferon; Sjögren’s syndrome.

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Conflict of interest statement

Alexis Collins, Dennis Lendrem, James Wason, Jessica Tarn, Nadia Howard-Tripp, Iris Bodewes, Marjan A. Versnel, Jacques-Eric Gottenberg, Raphaele Seror, Xavier Mariette and Wan-Fai Ng, all declare that they have no conflict of interest. ICMJE COI forms have been completed by all contributing authors.

Figures

Fig. 1
Fig. 1
Adjusted changes and 95% confidence limits for ESSPRI between Baseline and Week 12, Week 12 and Week 24. Footnote: sample sizes for both ESSPRI and ESSDAI. Scores were available for 14 LSB patients (9 Placebo, 5 HCQ), 32 HSB patients (18 Placebo, 14 HCQ), 22 DDF patients (11 Placebo, 11 HCQ) and 39 PDF patients (20 Placebo, 19 HCQ)
Fig. 2
Fig. 2
Adjusted changes and 95% confidence limits for the IFN Score between Baseline and Week 24 following adjustment for Baseline values. There are reductions in IFN scores in both the PDF and DDF subgroups for patients treated with HCQ. IFN scores were analysed for 9 LSB patients (7 Placebo, 2 HCQ), 16 HSB patients (8 Placebo, 8 HCQ), 15 DDF patients (8 Placebo, 7 HCQ) and 28 PDF patients (14 Placebo, 14 HCQ)
Fig. 3
Fig. 3
Adjusted changes and 95% confidence limits for ESSDAI between Baseline and Week 12, Week 12 and Week 24
See this image and copyright information in PMC

Comment in

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