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Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib.

ABSTRACT: Objectives:Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10?mg two times a day in patients with seropositive vs seronegative RA. Methods:Data were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]). 'Serotype' subgroups were: anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At month 3, ACR20/50/70 response rates, Disease Activity Score (DAS28-4[ESR])-defined remission (DAS28-4[ESR]<2.6) and low disease activity (LDA; DAS28-4[ESR]?3.2), changes from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36) physical functioning and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Safety endpoints were compared. Results:Baseline demographics/characteristics were similar across subgroups. Tofacitinib significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than anti-CCP-/RF- patients had ACR20/50/70 responses (ACR20/50: both tofacitinib doses; ACR70: 10?mg two times a day). SF-36 physical functioning improved in anti-CCP+/RF+, anti-CCP+/RF- and anti-CCP-/RF+ patients (both tofacitinib doses) and anti-CCP-/RF- patients (10?mg two times a day) vs placebo. More anti-CCP+/RF+ and anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(ESR) remission and LDA with tofacitinib 10?mg two times a day. Frequency of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across subgroups. Conclusion:Generally, tofacitinib efficacy (ACR20/50/70 responses) and safety were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical functioning appeared lower in anti-CCP- patients.

SUBMITTER: Bird P

PROVIDER: S-EPMC6397430 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib.

Bird Paul P Hall Stephen S Nash Peter P Connell Carol A CA Kwok Kenneth K Witcombe David D Thirunavukkarasu Krishan K

RMD open 20190223 1

<h4>Objectives</h4>Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA.<h4>Methods</h4>Data were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL S ...[more]

PMID: 30886732

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Project description:Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease.Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register.Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk.Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.

Project description:IntroductionRheumatoid arthritis (RA) is an inflammatory disease whose clinical phenotype largely depends on the presence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Seronegative RA appears to be a less severe disease, but this remains controversial. This study aimed to assess whether seronegative patients show a less severe disease than seropositive patients.MethodsA cross-sectional study was conducted on RA outpatients from a single center. Clinical activity scales, laboratory evaluations, and cardiovascular risk scores were assessed. Musculoskeletal ultrasound (US) examinations were performed.ResultsOne hundred and fourteen patients were enrolled. Eighty-five were seropositive (76% women) and 29 seronegative (93% women). Seropositive patients had a younger age at disease onset (43 ± 14 vs. 54 ± 11; p = 0.001) and used sulfasalazine (47 vs. 17%; p = 0.004) and glucocorticoids (36 vs. 10%; p = 0.007) more frequently. No differences in clinical activity scales and in 10-year cardiovascular risk were observed. Pathological US data were found more frequently in seropositive patients in the 2nd metacarpophalangeal (MCP) joint, both in grayscale (71 vs. 38%; p = 0.008) and in power Doppler (PD; 53 vs. 9%; p < 0.001); erosions (36 vs. 9%; p = 0.020) were also more frequent. We found greater severity of PD signals in the 2nd MCP and 3rd MCP joints of the seropositive patients, while synovitis severity was higher only in the 2nd MCP joints. The percentage of total joints with erosions (9 vs. 1%; p < 0.001) and 2nd MCP joints with erosions (25 vs. 7%; p < 0.001) was higher in seropositive patients.ConclusionRA patients show a differentiated phenotype according to their ACPA and RF status. In seronegative patients, RA begins later in life and has a lower requirement for antirheumatic therapies. On US evaluation, seropositive patients show more joint damage, especially in MCP joints. Despite this, long-term cardiovascular risk is similar among RA patients, regardless of their RF and ACPA status.

Dataset Information

Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib.

Publications

Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib.

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