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  1. Article ; Online: Lessons for rituximab therapy in patients with rheumatoid arthritis.

    Garcia-Montoya, Leticia / Villota-Eraso, Catalina / Yusof, Md Yuzaiful Md / Vital, Edward M / Emery, Paul

    The Lancet. Rheumatology

    2020  Volume 2, Issue 8, Page(s) e497–e509

    Abstract: B-cell depletion therapy is an effective option for the treatment of rheumatoid arthritis but often does not result in complete B-cell depletion. Complete B-cell depletion after rituximab treatment is associated with clinical response, and this outcome ... ...

    Abstract B-cell depletion therapy is an effective option for the treatment of rheumatoid arthritis but often does not result in complete B-cell depletion. Complete B-cell depletion after rituximab treatment is associated with clinical response, and this outcome leads to long-term maintenance of therapy. Low pretreatment plasmablast counts, concomitant treatment with disease-modifying antirheumatic drugs, no smoking exposure, the presence of anticitrullinated protein antibodies or rheumatoid factor, and a low interferon signature are all predictive of complete B-cell depletion and clinical response. Half of patients who initially show complete B-cell depletion and clinical response after rituximab treatment eventually lose responsiveness with further infusions. However three-quarters of these patients regain this outcome in their following treatment cycle, suggesting that loss of response is reversible and that patients can still benefit from rituximab retreatment. The efficacy of reduced doses of rituximab is being investigated, but preliminary results suggest that these strategies are best used for maintenance therapy, particularly in patients who suffer adverse events or who are at a high risk of infection. Infusion-related reactions are the most common adverse events associated with rituximab treatment, and monitoring of IgG concentrations is crucial, as low concentrations are correlated with an increased risk of infection.
    Language English
    Publishing date 2020-05-12
    Publishing country England
    Document type Journal Article ; Review
    ISSN 2665-9913
    ISSN (online) 2665-9913
    DOI 10.1016/S2665-9913(20)30033-3
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  2. Article ; Online: Gene Expression and Autoantibody Analysis Revealing Distinct Ancestry-Specific Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus.

    Carter, Lucy M / Alase, Adewonuola / Wigston, Zoe / Psarras, Antonios / Burska, Agata / Sutton, Emily / Yusof, Md Yuzaiful Md / Reynolds, John A / McHugh, Neil / Emery, Paul / Wittmann, Miriam / Bruce, Ian N / Vital, Edward M

    Arthritis & rheumatology (Hoboken, N.J.)

    2023  Volume 75, Issue 5, Page(s) 697–710

    Abstract: Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort ... ...

    Abstract Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort who were refractory to standard therapy.
    Methods: We evaluated baseline expression levels of transcripts known to associate with clinical features of SLE using a 96-probe TaqMan array and whole blood samples from 213 patients with active SLE who had been prospectively enrolled in the British Isles Lupus Assessment Group (BILAG) Biologics Register. We measured autoantibodies using immunoprecipitation and enzyme-linked immunosorbent assays. We determined responses to first-cycle rituximab at 6 months from treatment start in 110 SLE patients by assessing BILAG 2004 disease activity.
    Results: Interferon gene expression scores were lower in patients of European ancestry than in all other ancestry groups. The relationship between blood interferon gene expression scores and scores annotated to plasmablasts, neutrophils, myeloid lineage, inflammation, and erythropoiesis differed between patients of European and non-European ancestries. Hierarchical clustering revealed 3 distinct non-European ancestry patient subsets with stratified responses to rituximab that were not explained by sociodemographic and clinical variables, with responses lowest in an interferon-low, neutrophil-high cluster and highest in a cluster with high expression levels across all signatures (P < 0.001). Clusters in European ancestry patients did not predict response to rituximab but segregated patients by global disease activity and renal involvement. In both ancestral groups, interferon-high clusters were associated with U1 RNP/Sm antibodies.
    Conclusion: Ancestry appears central to the immunologic and clinical heterogeneity in SLE. These results suggest that ancestry, disease activity, and transcriptional signatures could each assist in predicting the effectiveness of B cell depletion therapies.
    MeSH term(s) Humans ; Rituximab/therapeutic use ; Autoantibodies ; B-Lymphocytes ; Treatment Outcome ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics ; Antibodies, Antinuclear ; Interferons ; Gene Expression
    Chemical Substances Rituximab (4F4X42SYQ6) ; Autoantibodies ; Antibodies, Antinuclear ; Interferons (9008-11-1)
    Language English
    Publishing date 2023-03-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42404
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  3. Article ; Online: Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study.

    Mahmoud, Khaled / Zayat, Ahmed S / Yusof, Md Yuzaiful Md / Dutton, Katherine / Teh, Lee Suan / Yee, Chee-Seng / D'Cruz, David / Ng, Nora / Isenberg, David / Ciurtin, Coziana / Conaghan, Philip G / Emery, Paul / Edwards, Christopher J / Hensor, Elizabeth M A / Vital, Edward M

    Rheumatology (Oxford, England)

    2021  Volume 60, Issue 11, Page(s) 5194–5204

    Abstract: Objectives: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of ... ...

    Abstract Objectives: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis.
    Methods: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM.
    Results: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients.
    Conclusion: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.
    MeSH term(s) Adult ; Female ; Glucocorticoids/therapeutic use ; Humans ; Longitudinal Studies ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/diagnostic imaging ; Lupus Erythematosus, Systemic/drug therapy ; Male ; Methylprednisolone/therapeutic use ; Middle Aged ; Prospective Studies ; Synovitis/diagnostic imaging ; Synovitis/drug therapy ; Synovitis/etiology ; Ultrasonography
    Chemical Substances Glucocorticoids ; Methylprednisolone (X4W7ZR7023)
    Language English
    Publishing date 2021-03-30
    Publishing country England
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keab288
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    Zs.MO 497: Show issues

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  4. Article ; Online: The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation.

    Gordon, Rachael A / Nguyen, Yann / Foulquier, Nathan / Beydon, Maxime / Gheita, Tamer A / Hajji, Raouf / Sahbudin, Ilfita / Hoi, Alberta / Ng, Wan-Fai / Mendonça, Jose Alexandre / Wallace, Daniel J / Shea, Beverley / Bruyn, George Aw / Goodman, Susan M / Fisher, Benjamin A / Baldini, Chiara / Torralba, Karina D / Bootsma, Hendrika / Akpek, Esen K /
    Karakus, Sezen / Baer, Alan N / Chakravarty, Soumya D / Terslev, Lene / D'Agostino, Maria-Antonietta / Mariette, Xavier / DiRenzo, Dana / Rasmussen, Astrid / Papas, Athena / Montoya, Cristina / Arends, Suzanne / Yusof, Md Yuzaiful Md / Pintilie, Ionut / Warner, Blake M / Hammitt, Katherine M / Strand, Vibeke / Bouillot, Coralie / Tugwell, Peter / Inanc, Nevsun / Andreu, José Luis / Wahren-Herlenius, Marie / Devauchelle-Pensec, Valerie / Shiboski, Caroline H / Benyoussef, Anas / Masli, Sharmila / Lee, Adrian Y S / Cornec, Divi / Bowman, Simon / Rischmueller, Maureen / McCoy, Sara S / Seror, Raphaele

    Seminars in arthritis and rheumatism

    2024  Volume 65, Page(s) 152378

    Abstract: Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for ... ...

    Abstract Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.
    MeSH term(s) Humans ; Treatment Outcome ; Sjogren's Syndrome/therapy ; Pain ; Fatigue
    Language English
    Publishing date 2024-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120247-9
    ISSN 1532-866X ; 0049-0172
    ISSN (online) 1532-866X
    ISSN 0049-0172
    DOI 10.1016/j.semarthrit.2024.152378
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