Open-Label Extension Study to Evaluate the Safety of Efgartigimod in Adult Patients With Primary Sjögren's Syndrome

An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or any other medically important event. Treatment-emergent adverse events (TEAEs) were defined as AEs with onset on or after the first administration of study drug up to and including 60 days after the last study drug administration. Adverse events in the 'Infections and infestations' SOC were defined as AE of Special Interest (AESIs) because efgartigimod causes a transient reduction in total IgG levels.

A composite of relevant endpoints for Sjögren's syndrome (CRESS) measures systemic disease activity, patient-reported symptoms, tear gland function, salivary gland function, and serology, developed to assess treatment efficacy in participants with SjD. A responder is defined as improvement in at least 3 of the above mentioned 5 items of CRESS. The score ranges from 0 to 9 (higher score = worse symptoms). Responder rates for the efgartigimod-efgartigimod group in the follow-up study are supplemental to those in the antecedent study (ARGX-113-2106). Because responders from the ARGX-113-2106 study (mainly in the efgartigimod-efgartigimod group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

European alliance of associations for rheumatology (EULAR) SjD activity index (ESSDAI) measures systemic disease activity in 12 domains. The activity levels of each domain are multiplied by their respective weights to obtain the total score between 0 and 123 (higher score = worse symptoms). Minimally clinically important improvement in ESSDAI was defined as improvement of at least 3 points in ESSDAI score at Weeks 24 and 48. Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106. Responder rates for the efg-efg group in the follow-up study are supplemental to those in the ARGX-113-2106 study. Because responders from the ARGX-113-2106 study (mainly in the efg-efg group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

ESSDAI measures systemic disease activity in participants with SjD and consists of 12 domains. The activity levels of each domain (range: 0-3 points) are multiplied by their respective weights (range: 1-6 points) to obtain the total score between 0 and 123 (higher score = worse symptoms). Low disease activity in ESSDAI was defined as ESSDAI score of less than 5 at Weeks 24 and 48. Responder rates for the efgartigimod-efgartigimod group in the follow-up study are supplemental to those in the antecedent study (ARGX-113-2106). Because responders from the ARGX-113-2106 study (mainly in the efgartigimod-efgartigimod group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

Clinical EULAR Sjögren's syndrome disease activity index (clinESSDAI) includes same 11 organ-specific domains as ESSDAI but with different domain weighting and this scale does not have biological domain.This way any change in clinESSDAI score reflects disease specific features irrespective of B-cell activity. clinESSDAI score ranges between 0-135 (higher score=worse symptoms).Minimal clinically important improvement in clinESSDAI was defined as improvement of at least 3 points in clinESSDAI score at Weeks 24 and 48.Baseline=last available non-missing measurement from parent study ARGX-113-2106.Responder rates for efgartigimod-efgartigimod group in follow-up study are supplemental to those in antecedent study (ARGX-113-2106).Because responders from ARGX-113-2106 study (mainly in efgartigimod-efgartigimod group) potentially started ARGX-113-2211 with lower baseline scores,further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

clinESSDAI includes the same 11 organ-specific domains as ESSDAI but with different domain weighting and this scale does not have the biological domain. This way any change in clinESSDAI score reflects disease specific features irrespective of B-cell activity. The clinESSDAI score ranges between 0-135 (higher score = worse symptoms). Low disease activity in clinESSDAI was defined as clinESSDAI score of less than 5 at Weeks 24 and 48. Responder rates for the efgartigimod-efgartigimod group in the follow-up study are supplemental to those in the antecedent study (ARGX-113-2106). Because responders from the ARGX-113-2106 study (mainly in the efgartigimod-efgartigimod group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

EULAR Sjögren's syndrome patient-reported index (ESSPRI) is a questionnaire developed to measure self-reported symptoms in participants with SjD and consists of 3 items that measure dryness, fatigue, and pain. The total global score ranges from 0 to 10 by averaging the numeric scores for pain, fatigue, and dryness, with higher scores indicating more symptoms. Minimal clinically important improvement in ESSPRI was defined as decrease of 1 point or at least >=15% at Weeks 24 and 48. Baseline was defined as the last available non-missing measurement from the study ARGX-113-2106. Responder rates for the efg-efg group in the follow-up study are supplemental to those in the ARGX-113-2106 study. Because responders from the ARGX-113-2106 study (mainly in the efg-efg group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this measure is inherently challenging due to biological and clinical limitations.

ESSDAI measures systemic disease activity in participants with SjD and consists of 12 domains: 11 organ-specific domains (cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system, central nervous system, hematological, glandular, constitutional, and lymphadenopathic) and 1 biological domain reflecting B-cell activity that contributes to disease activity level scoring. The activity levels of each domain (range: 0-3 points) are multiplied by their respective weights (range: 1-6 points) to obtain the total score between 0 and 123 (higher score = worse symptoms). Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106.

clinESSDAI includes the same 11 organ-specific domains as ESSDAI but with different domain weighting and this scale does not have the biological domain. This way any change in clinESSDAI score reflects disease specific features irrespective of B-cell activity. The clinESSDAI score ranges between 0-135 (higher score = worse symptoms). Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106.

ESSPRI is a questionnaire developed to measure self-reported symptoms in participants with SjD and consists of 3 items that measure dryness, fatigue, and pain. Each item includes a numeric rating scale ranging from 0: no symptoms (dryness, fatigue, or pain) to 10: maximal imaginable (dryness, fatigue, or pain). The total global score ranges from 0 to 10 and the ESSPRI is calculated by averaging the numeric scores for pain, fatigue, and dryness, with higher scores indicating more symptoms. Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106.

Sjögren's tool for assessing response (STAR) is a composite endpoint assessing multiple clinically relevant disease features. A STAR responder is defined as a participant with a score of at least 5 points. Due to the weighting, participant must be a responder on either systemic disease activity (ESSDAI), patient-reported symptoms (ESSPRI), or both to be an overall STAR responder. The score ranges between 0 and 9 (higher score = worse outcome). Responder rates for the efgartigimod-efgartigimod group in the follow-up study are supplemental to those in the antecedent study (ARGX-113-2106). Because responders from the ARGX-113-2106 study (mainly in the efgartigimod-efgartigimod group) potentially started the ARGX-113-2211 with lower baseline scores, further improvement on this efficacy measure is inherently challenging due to clinical and biological limitations.

Blood samples were collected at indicated timepoints to assess the total Immunoglobulin (Ig)G levels in serum. Total IgG concentrations were quantified using validated methods at a diagnostical laboratory. Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106.

Blood samples were collected at indicated timepoints to assess serum autoantibodies: anti-Ro/Sjögren's syndrome-related antigen A (SS-A) and anti-La/Sjögren's syndrome-related antigen B (SS-B). Baseline was defined as the last available non-missing measurement from the parent study ARGX-113-2106.

Serum samples were collected at indicated timepoints to assess the pharmacokinetic (PK) profile of efgartigimod.

Blood samples were collected to assess anti-drug antibodies (ADAs) against efgartigimod. Samples were analyzed by the designated laboratory in a 3-tiered approach using validated immunogenicity assays. ADA incidence included total number of participants with treatment-boosted and treatment-induced ADA. Treatment-boosted ADA was defined as participants who had a baseline positive sample and the titer value increased 4-fold or more compared to baseline. Treatment-induced ADA was defined as participants who had a baseline negative sample and at least 1 positive post-baseline samples. Number of participants with ADA incidence is presented here.