Dr. C. Balakrishnan, Consultant Rheumatologist, Hinduja Hospital, Mumbai

1. The use of MRI-detected synovitis to determine the number of involved joints for the 2010 ACR/EULAR classification criteria for Rheumatoid Arthritis – is it of additional benefit?

Ann Rheum Dis. Aug 2018

Objectives:

To assess the value of MRI-detected synovitis to determine the number of involved joints on the performance of the 2010-ACR/EULAR classification criteria for rheumatoid arthritis (RA).

Methods:

277 patients with a clinical suspicion of RA consecutively included in the Leiden Early Arthritis Clinic (EAC) cohort underwent 1.5T MRI of MCP, wrist, and MTP joints. Test characteristics of the 2010 criteria were calculated when the number of involved joints was determined with and without including MRI-detected synovitis. Two outcomes were studied: Disease-modifying anti-rheumatic drug (DMARD) initiation and 1987-criteria fulfilment during the first year.

Results:

At baseline, 143 patients were classified as having RA. When MRI-detected synovitis was considered, 14 patients additionally fulfilled the 2010 criteria. Of these, 64% (9/14) started DMARDs. When MRI-detected synovitis was also used to determine the number of involved joints, the sensitivity changed from 62% to 67%; the specificity from 90% to 84%; and the AUC from 0.76 to 0.75. The net reclassification index was 2.4%. When fulfilling the 1987 criteria was used as the outcome, results were similar.

Conclusion:

We found no scientific support that the use of MRI-detected synovitis is of additional benefit for the performance of the 2010 classification criteria.

2. Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA

Ann Rheum Dis. Aug 2018

Objective:

To determine the reasons of methotrexate (MTX) discontinuation, frequency of adverse events (AEs), and whether the time in inactive disease before MTX withdrawal disease is associated with the risk of disease flare.

Methods:

Patients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX were prospectively observed in the national JIA biologic register Biologika in der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up register Juvenile arthritis Methotrexate/Biologics long-term Observation. Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, flare after MTX discontinuation by re-occurrence of at least moderate disease activity, or restart of treatment with a disease-modifying anti-rheumatic drug.

Results:

MTX treatment was initiated in 1514 patients after a mean disease duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness (36.9%) and achieving inactive disease (32.1%) were the most common reasons. Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up. The likelihood of a flare was a function of time in inactive disease prior to MTX discontinuation (HR 0.95; 95% CI 0.92–0.97). Patients with inactive disease for more than 12 months had a significantly lower flare rate (58 of 119, 48.7%; HR 0.48; 95% CI 0.34–0.69). The most frequently reported AE was MTX intolerance, including nausea, aversion, and vomiting, accounting for 441 events (13.0 events/100 exposure years) in 307 (20.3%) patients.

Conclusion

Patients who had an inactive disease for at least 12 months before MTX discontinuation had a significantly lower flare rate.

3. Tofacitinib is associated with attainment of the minimally important reduction in axial magnetic resonance imaging inflammation in ankylosing spondylitis patients.

Rheumatology (Oxford). Aug 2018.

Objective:

Minimally important changes (MICs) for SPondyloArthritis Research Consortium of Canada (SPARCC) MRI scores are ⩾2.5 and ⩾5 for SI joint and spine, respectively. This post-hoc analysis assessed the achievement of MIC in SPARCC scores in biologically naive patients with AS treated with tofacitinib or placebo, and correlation with clinical responses.

Methods

Adult AS patients in a 12-week phase II study (n=207) were randomized in a ratio of 1:1:1:1 to tofacitinib 2, 5, or 10 mg twice daily (BID) or placebo. Minimally important changes in SPARCC SI joint and spine scores were assessed for patients with available MRI data (N=164; 79%). Clinical endpoints at week 12, including Assessment of SpondyloArthritis international Society 20% improvement (ASAS20), were compared between patients achieving/not achieving MIC.

Results:

A greater proportion of patients achieved MIC with tofacitinib 2, 5, and 10 mg BID vs. placebo for SI joint (28.6, 38.6, 29.6 vs. 11.8%) and spine scores (29.3, 36.4, 40.9 vs. 11.8%). Generally, a greater proportion of patients treated with tofacitinib 2, 5, and 10 mg BID or placebo, respectively, who achieved MIC for SI joint and spine scores, achieved ASAS20 (SI joint: 75.0, 88.2, 69.2, 75.0%; spine: 91.7, 85.7, 72.2, 75.0%) vs. patients who did not achieve MIC (SI joint: 51.7, 84.0, 58.1, 48.3%; spine: 46.4, 85.7, 53.8, 48.3%). Numerically greater responses were seen in those patients achieving vs. not achieving MIC across a range of other efficacy assessments.

Conclusion

Approximately one-third of tofacitinib-treated AS patients experienced clinically meaningful reductions in spinal MRI inflammation at week 12. Patients achieving MIC for MRI inflammation showed a greater clinical response.

4. A novel lupus activity index accounting for glucocorticoids: SLEDAI-2K glucocorticoid index

Rheumatology (Oxford). Aug 2018.

Objective:

To develop and validate a modification of SLEDAI-2K to accurately describe disease activity while accounting for glucocorticoid (GC) doses.

Methods:

The first two phases focused on the development of the index. Phase 1: Identification of scenarios of real patients seen prospectively in a longitudinal cohort. Phase 2: Derivation of an equation that explains the association between SLEDAI-2K and GC doses using physician global assessment as the external construct. Phase 3: Comparison of SLEDAI-2K and SLEDAI-2K GC (SLEDAI-2KG), using different cutoff points (4–7), in identifying responders in response to therapy.

Results:

In phase 1, 150 scenarios with different organ involvement and a range of GC doses were identified. In phase 2, three rheumatologists ranked disease activity using physician global assessment. A quadratic linear regression model relating GC doses and SLEDAI-2K resulted in the following equation: SLEDAI-2KG score = SLEDAI-2K score + [0.32 × GC – 0.0031 × GC2]. The weighted score of different GC doses was derived. In phase 3, SLEDAI-2KG identified more responders in a total of 111 patients at 6 months (84 vs. 93%) and at 12 months (76 vs. 92%) compared with SLEDAI-2K. SLEDAI-2KG performances were superior to SLEDAI-2K with all cutoff points (5–7).

Conclusion:

We developed a modification of SLEDAI-2K, namely SLEDAI-2KG, that describes disease activity while accounting for the GC-dose category. SLEDAI-2KG identifies more responders compared with SLEDAI-2K.

5. Correlation between bone quality and microvascular damage in systemic sclerosis patients

Rheumatology (Oxford). Aug 2018.

Objective:

SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, using trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT).

Methods:

Eighty-four SSc patients, 98 RA patients, and 60 CNT were studied. BMD (g/cm2) of the lumbar spine (L1–L4) was analyzed with a DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. Nailfold videocapillaroscopy patterns were analyzed.

Results:

A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA, and BMD was found to be significantly lower compared with that in the CNT (p<0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (p<0.001). Trabecular bone score values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs. active and early pattern, p<0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (p=0.238).

Conclusion:

The data obtained showed a significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern).

6. Characterization of the nasal microbiota in granulomatosis with polyangiitis

Ann Rheum Dis. Oct 2018.

Objective:

Prior studies have suggested a potential link between nasal microbes and GPA; Wegener’s, however, these studies relied on culture-dependent methods. This study comprehensively examined the entire community of nasal microbiota (bacteria and fungi) in participants with GPA compared with healthy controls using deep-sequencing methods.

Methods:

16S rRNA and internal transcribed spacer gene sequencing were performed on nasal microbial DNA isolated from nasal swabs of 60 participants with GPA and 41 healthy controls. Alpha and beta diversity as well as the relative abundance of the most abundant bacterial and fungal taxa were assessed. The effects of covariates, including disease activity and immunosuppressive therapies on microbial composition, were evaluated.

Results:

Compared with controls, participants with GPA had a significantly different microbial composition (weighted UniFrac p=0.04) and lower relative abundance of Propionibacterium†acnes†and Staphylococcus†epidermidis†(for both, false discovery rate-corrected p=0.02). Disease activity in GPA was associated with a lower abundance of fungal order Malasseziales†compared with participants with GPA in remission (p=0.04) and controls (p=0.01). Use of a non-GC immunosuppressive therapy was associated with “healthy” nasal microbiota while participants with GPA who were off immunosuppressive therapy had more dysbiosis (weighted UniFrac p=0.01). No difference in the relative abundance of Staphylococcus aureus was observed between GPA and controls.

Conclusion:

GPA is associated with an altered nasal microbial composition, at both the bacterial and fungal levels. Use of immunosuppressive therapies and disease remission are associated with healthy microbial communities.