With the ongoing expansion of the therapeutic landscape, treatment management for chronic inflammatory rheumatic diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) is also changing. The diseases are often associated with physical and psychological limitations and remission is the primary treatment goal in order to improve the patient’s quality of life.1-5 Individual treatment decisions play an important role here.6 At the annual congress of the Swiss Society of Rheumatology (SGR), treatments for RA, PsA and AS were discussed at an interactive symposium.
Rheumatic diseases can be associated with extra-articular manifestations and comorbidities that increase the risk of mortality.1-3 RA patients show an increased risk of cardiovascular events, which are also more often fatal compared to the general population.7 Up to 30% of the risk of cardiovascular disease in men and women is associated with the disease characteristics of RA. Achieving remission therefore not only improves the quality of life (QoL) of RA patients, but also reduces the risk of cardiovascular events as well as serious infections and malignancies.8-12 In PsA, a heterogeneous disease characterized by musculoskeletal manifestations in the peripheral joints, in the spine and on the skin, the QoL of those affected is also severely restricted. About two-thirds of patients have more than one active domain; these multiple manifestations further increase the disease burden.13, 14 Individual treatment decisions are of great importance here.6 AS is also a chronic inflammatory, progressive and heterogeneous musculoskeletal disorder associated with inflammatory back pain and stiffness of the spine, primarily affecting the axial skeleton and associated with a severe physical, psychological and socioeconomic burden for those affected.15, 16 In contrast to other rheumatic diseases, there is a limited range of treatment options for AS that show limited clinical efficacy and include tumor necrosis factor (TNF), interleukin (IL)-17 and Janus kinase (JAK) inhibitors.17
Benefit-risk profile of upadacitinib in RA
In RA patients who had shown an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), the JAK inhibitor (JAKi) upadacitinib (UPA, RINVOQ®) achieved better efficacy in achieving remission than the active substance adalimumab (ADA) in pivotal studies.18 In more refractory patients who had already responded inadequately to a biologic (bDMARDs), UPA was also superior to treatment with abatacept.19 A benefit-risk analysis based on a hypothetical cohort of 100 methotrexate (MTX)-refractory RA patients showed that treatment with UPA + MTX resulted in better remission rates in the DAS28-CRP* score than treatment with ADA + MTX. The rates of major adverse cardiovascular events (MACE), malignancies and venous thromboembolism (VTE) were comparable between treatments.20
A recently published analysis of RA patients aged ≥50 years and with at least one cardiovascular risk factor examined a similar population to the ORAL Surveillance Study.21 This analysis showed that the incidence of MACE, malignant tumors (except non-melanoma skin cancer (NMSC)) and VTE was generally higher in populations with increased cardiovascular risk. However, the incidence of these adverse events was also comparable between the respective therapy with UPA, ADA and MTX(Fig. 1).22 Overall, UPA showed a positive benefit-risk profile in the studies conducted.20, 22
Fig. 1: Risk-benefit analysis of JAKi in RA. A) Efficacy of UPA in clinical head-to-head phase 3 trials. B) Safety of UPA in RA patients ≥50 years and with ≥1 cardiovascular risk factor.
ABA, abatacept; ADA, adalimumab; CV, cardiovascular; DAS28, disease activity score based on 28 joints; EAIR, exposure adjusted incidence rate; EOW, every other week; EXCL, excluded; IV, intravenous; IR, inadequate response; MACE, major adverse cardiovascular events; MTX, methotrexate; NMSC, non-melanocytic skin cancer; PBO, placebo; QD, once daily; PY, patient years; RA, rheumatoid arthritis; UPA, upadacitinib.
Adapted from 18, 19, 23
Risankizumab improves QoL in different patient groups24
Risankizumab (RZB, SKYRIZI®) is a selective inhibitor of the p19 subunit of interleukin-23, which has shown robust and long-lasting efficacy in all manifestations of PsA(Fig. 2).24, 25 RZB achieved good efficacy in patients with both limited and intensive joint involvement.26 Furthermore, treatment with RCB led to a significant improvement in QoL in various patient groups.24 Given the heterogeneity of PsA, treatment decisions should be individually tailored and the efficacy of the drugs used on musculoskeletal and extra-musculoskeletal manifestations should be taken into account. The patient’s preference for oral dosing over subcutaneous injections at longer intervals should also be taken into account in the treatment decision.6 With the 12-weekly dosing regimen, RZB can bring about sustained improvements in musculoskeletal manifestations and skin appearance for PsA patients and shows a favorable safety profile.27
Since September 2023, RZB has also been approved for the treatment of adult patients with moderate to severe active Crohn’s disease who have responded inadequately to conventional therapy or a biologic.28
Fig. 2: RZB shows efficacy in all manifestations of PsA.
aPatientswith ≥ 3% BSA at baseline; bPatientswith LEI > 0 at baseline; cPatientswith LDI > 0 at baseline; dPatientswith spondylitis at baseline.
ACR50, American College of Rheumatology 50% improvement; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BSA: body surface area; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MCID, minimal clinically important difference; MDA, minimal disease activity; PASI 90, Psoriasis Area Severity Index 90% improvement; PsA, psoriatic arthritis; PsA-mTSS, psoriatic arthritis modified total Sharp score; Q12W, every 12 weeks.
Adapted from 24, 25
Upadacitinib in the AS
A recent network meta-analysis indicates comparable efficacy of all previously approved treatments for AS(Fig. 3).17 In contrast, UPA consistently showed numerically higher response rates, such as reaching ASAS40*, and a lower number-needed-to-treat (NNT) in biologic-naïve AS patients, as well as AS patients who had inadequately responded to biologics or TNF inhibitors.17 With its novel mechanism of action, UPA offers a rapid response, improved remission rates (or low disease activity) and a consistent safety profile with once-daily oral administration in the treatment of AS.29
Conclusion
The treatment landscape for rheumatic diseases is growing and offers more and more potential for individual treatment decisions. These should take into account the heterogeneity of the diseases as well as the patient’s wishes in order to achieve remission and improve the QoL of those affected in a sustainable and long-term manner.6
* DAS28-CRP, score for disease activity based on 28 joints; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; ASAS40, Assessment of Spondyloarthritis International Society Improvement ≥40%
Text: Dr. sc. nat. Katja Becker
Brief technical information RINVOQ® and SKYRIZI®.
This article was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, Cham.
CH-SKZ-230006_10/2023
This article has been released in German.
Article online since 21.11.2023
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27 Current technical information on SKYRIZI® (rizankizumab) at www.swissmedicinfo.ch.
28. current expert information on SKYRIZI® (risankizumab) Crohn’s disease at www.swissmedicinfo.ch.
29 Current technical information for RINVOQ® (upadacitinib) at www.swissmedicinfo.ch.
The references can be requested by professionals at medinfo.ch@abbvie.com.
