Optimising treatment outcomes in people living with systemic lupus erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic, autoimmune disease with heterogeneous symptoms, mainly affecting females in their reproductive years. The aim of this thesis was to expand the current understanding of how to optimise treatment outcomes in patients with SLE.

In Studies I–III, we performed post-hoc analyses on two phase 3 clinical trials where we explored therapeutic targets and investigated whether these targets were beneficial to the patients’ health-related quality of life (HRQoL). In Studies IV–V, we studied medication non-adherence to identify determinants and facilitators potentially improving patients’ adherence to medications to expand the current understanding of medication non-adherence in Sweden.

In Study I, we investigated to which extent remission was achievable in SLE patients included in two clinical trials; we evaluated the attainability and suitability of the different definitions as outcome measures and found that remission was overall difficult to attain. The least stringent definition of remission was achieved by 10.5% of participants. That remission definition was based on the SLE disease activity index-2000 (SLEDAI-2K).

In Study II, we examined the attainability of clinical SLEDAI-2K=0 which is based on one index only. We compared clinical SLEDAI-2K=0 to lupus low disease activity state (LLDAS) and SLE-Responder Index (SRI)-4, two composite measurements. The attainability of cSLEDAI-2K=0 (34.5%) was more frequent than the LLDAS (8.6%) but less frequent than SRI-4 (45.1%) and yielded the strongest correlation with the physician’s global assessment (PGA) compound in remission definitions (PGA<0.5; rφ=0.36, P<0.001). Our findings indicated that a definition based on one single index could be a pragmatic outcome measure in SLE studies.

In Study III, we evaluated whether patients in remission or lupus low disease activity state experience a benefit in HRQoL compared to not being in remission or lupus low disease activity state. We found that less time in remission is required compared to lupus low disease activity state to achieve a benefit in HRQoL. Also, sustained remission or lupus low disease activity state yielded a greater HRQoL benefit than when these states were interrupted. It was more difficult to detect a clinically important difference in mental compared to physical HRQoL.

Study IV was a survey study with data collected in Sweden. When assessing non-adherence with a generic instrument, we found that 6.6%, 6.3%, and 10.2% were non-adherent to antimalarial agents (AMA), glucocorticoids (GCs), and SLE-related medications other than AMA or GCs, respectively. Interestingly, non-adherence to anti-rheumatic medications assessed with a rheumatic disease-specific instrument showed that 66.8% of the patients were non-adherent. We identified patients’ negative views on medications and patients’ experience of poor HRQoL to be associated with medication non-adherence.

From our interviews in Study V, we identified patient-, healthcare-, medication-, and disease-related barriers to medication adherence. Our suggested facilitators included improvements in communication between healthcare providers and patients, patient education, accessibility to healthcare, optimisation of the transition from paediatric to adult care, medication reconciliation, psychosocial support, and lastly, inclusion of family members in the care of the patients.

List of scientific papers

I. Ioannis Parodis*, Sharzad Emamikia*, Alvaro Gomez, Cidem Gentline, Elizabeth V Arkema, Katerina Chatzidionysiou, Ronald F van Vollenhoven. Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials. Lancet Rheumatology. 2019;1:163-73. *Equal contribution.
https://doi.org/10.1016/S2665-9913(19)30049-9

II. Ioannis Parodis, Sharzad Emamikia, Alvaro Gomez, Iva Gunnarsson, Ronald van Vollenhoven, Katerina Chatzidionysiou. Clinical SLEDAI-2K zero may be a pragmatic outcome measure in SLE studies. Expert Opinion on Biological Therapy. 2019 Feb; 19(2):157-168.
https://doi.org/10.1080/14712598.2019.1561856

III. Sharzad Emamikia, Shereen Oon, Alvaro Gomez, Julius Lindblom, Alexander Borg, Yvonne Enman, Eric Morand, David Grannas, Ronald F. van Vollenhoven, Mandana Nikpour, Ioannis Parodis. Impact of remission and low disease activity on health-related quality of life in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2022;10.1093.
https://doi.org/10.1093/rheumatology/keac185

IV. Sharzad Emamikia, Alvaro Gomez, Theodor Ådahl, Gunilla von Perner, Yvonne Enman, Katerina Chatzidionysiou, Elizabeth V Arkema, Ioannis Parodis. Medication adherence in patients with systemic lupus erythematosus: results from a Swedish survey. [Manuscript]

V. Sharzad Emamikia, Cidem Gentline, Yvonne Enman, Ioannis Parodis. How can we enhance adherence to medications in patients with systemic lupus erythematosus? Results from a qualitative study. Journal of Clinical Medicine. 2022 Mar 27;11(7):1857.
https://doi.org/10.3390/jcm11071857