Maintenance of clinical remission in early axial spondyloarthritis following certolizumab pegol dose reduction

Background:  The best strategy for maintaining clinical remission in patients with axial spondyloarthritis (axSpA) has not been defined. C-OPTIMISE compared dose continuation, reduction and withdrawal of the tumour necrosis factor inhibitor certolizumab pegol (CZP) following achievement of sustained remission in patients with early axSpA.  Methods: C-OPTIMISE was a two-part, multicentre phase 3b study in adults with early active axSpA (radiographic or non-radiographic). During the 48-week open-label induction period, patients received CZP 200 mg every 2 weeks (Q2W). At Week 48, patients in sustained remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.5 at any time point) during the double-blind period.  Results: At Week 48, 43.9% (323/736) patients achieved sustained remission, of whom 313 were randomised to CZP full maintenance dose, CZP reduced maintenance dose or placebo. During Weeks 48 to 96, 83.7% (87/104), 79.0% (83/105) and 20.2% (21/104) of patients receiving the full maintenance dose, reduced maintenance dose or placebo, respectively, were flare-free (p<0.001 vs placebo in both CZP groups). Responses in radiographic and non-radiographic axSpA patients were comparable.  Conclusions: Patients with early axSpA who achieve sustained remission at 48 weeks can reduce their CZP maintenance dose; however, treatment should not be completely discontinued due to the high risk of flare following CZP withdrawal.  Trial registration number: NCT02505542, ClinicalTrials.gov

Instrument selection for the ASAS core outcome set for axial spondyloarthritis

OBJECTIVES: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA). METHODS: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS. RESULTS: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments. CONCLUSIONS: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials

Results of the worldwide, cross-sectional ASAS-PerSpA study

Objectives: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. Methods: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. Results: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%). Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). Conclusion: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.publishersversionpublishe

Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis

Background. Recent works have suggested a possible link between IL-33 and B-cell biology. We aimed to study in different cohorts and with an accurate ELISA assay the possible association between serum IL-33 detection and response to rituximab (RTX) in rheumatoid arthritis (RA) patients. Method. Serum IL-33, rheumatoid factor (RF), anti-citrullinated cyclic peptide antibodies (anti-CCP), high serum IgG level were assessed in 111 RA patients receiving a first course of 2 grams RTX (cohort 1) in an observational study and in 74 RA patients treated with the same schedule in routine care (cohort 2). Uni and multivariate analyzes identified factors associated with a European League Against Rheumatism response at 24 weeks. Results. At week 24, 84/111 (76%) and 54/74 (73%) patients reached EULAR response in the cohorts 1 and 2, respectively. Serum IL-33 was detectable in only 33,5% of the patients. In the combined cohorts, presence of RF or anti-CCP (OR 3.27, 95%CI [1.13-9.46]; p=0.03), high serum IgG (OR 2.32, 95%CI [1.01-5.33]; p=0.048) and detectable serum IL-33 (OR 2.40, 95%CI [1.01-5.72]; p=0.047) were all associated with RTX response in multivariate analysis. Combination of these 3 factors increased the likelihood to response to RTX. When serum IL-33 detection was added to seropositivity and serum IgG level, 100% of the patients with the 3 risk factors (corresponding to 9% of the population) responded to RTX (OR versus patients with none of the 3 risk factors = 29.61; 95% CI [1.30-674.79] p=0.034) Conclusion. Detectable serum IL-33 may predict clinical response to RTX, independently of and synergistically with autoantibodies and serum IgG level