BackgroundTofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA).ObjectivesTo describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies.MethodsData were analysed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analysed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analysed over 12 months in pts randomised to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomised to PBO were excluded from this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiac events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications.ResultsC1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomised to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomised to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]) and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]).ConclusionsTofacitinib was well tolerated in pts with PsA, with a safety profile consistent to that seen in RA; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA.AcknowledgementsThese studies were sponsored by Pfizer Inc. Editorial support was provided by C Viegelmann of CMC and was funded by Pfizer Inc.Disc...

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease can lead to many clinical syndromes. One syndrome simulates rheumatoid arthritis and is thus called "pseudo-rheumatoid arthritis." Since some patients have true rheumatoid arthritis with CPPD crystal deposition disease, the clinician may have difficulty differentiating those patients from others who have the pseudo-rheumatoid syndrome. Such a diagnostic problem can be solved radiographically. Eleven patients with CPPD crystal deposition disease were studied; five had true rheumatoid arthritis and six had pseudo-rheumatoid arthritis. Because osseous erosions were not apparent in the arthropathy of uncomplicated CPPD crystal deposition disease, the detection of skeletal erosive changes indicated a true rheumatoid arthritis process.

OBJECTIVES: This paper reviews current approaches to defining clinically meaningful change in health‐related quality of life (HRQOL). METHODS: Definitions of clinically meaningful change are discussed. Psychometric properties of HRQOL instruments necessary for identifying clinically meaningful change are identified. Two broad methods for identifying clinically meaningful change are contrasted: anchor‐based methods and distribution‐based methods. Anchor‐based methods include forced‐choice paradigms, global change ratings, receiver operating characteristic techniques, goal attainment scaling and external event methods. Distribution‐based methods include individual effect size, the Guyatt responsiveness index, the Jacobson‐Traux reliable‐change index (and subsequent variations), standard error of measurement, and hierarchical linear modeling. Strategies for validating clinically meaningful change measures are discussed. RESULTS: Anchor‐based and distribution‐based methods have both advantages and limitations, and neither appears superior to the other. Anchor‐based methods provide a source for external validation, but are dependent on the specific anchors being used. Distribution‐based methods provide a statistical basis for decision‐making, but may vary on the basis of sample characteristics. CONCLUSIONS: The use of multiple methods to define clinically meaningful change is strongly recommended. Factors to consider in defining clinically meaningful change include the severity of the baseline value, the direction of change, and the importance of the change to the individual.

BACKGROUND: Health‐related quality of life (HR‐QOL) measures have been used to study the impact of disease activity in patients with rheumatoid arthritis (RA). The objective of this study was to evaluate the correlation between SF‐36 scales, physical function (PF), role physical (RP) and bodily pain (BP) and Rapid Assessment of Disease Activity in Rheumatology (RADAR). METHODS: Baseline data was analyzed from the Study of New Onset Rheumatoid Arthritis (S.O.N.O.R.A.SM), a 5‐year prospective, longitudinal, inception cohort study to document long‐term functional, clinical, and humanistic outcomes and patterns of treatment in patients with new onset rheumatoid arthritis. Baseline data collection consisted of RADAR and SF‐36 via telephone interviews by trained interviewers. To assess the correlation, Pearson product moment correlation coefficients were calculated. RESULTS: One hundred thirty‐one patients completed the baseline survey. Mean age of the sample was 56 years; 78% were female; 82% were Caucasian. SF‐36's PF, RP, and BP scales had means of 54 (SE = 0.02), 31 (SE = 0.03), and 47 (SE = 0.02), respectively. Mean scores for RADAR items were 7.2 (SE = 0.22) for “arthritis activity over the past 6 months (AA6M)”, 4.9 (SE = 0.23) for “arthritis activity today (AAT)”, 4.2 (SE = 0.22) for “arthritis pain today (APT)”, and 2.6 (SE = 0.15) for “morning stiffness today (MST)”. SF‐36's PF scale correlated with AA6M (r = 0.39, p < 0.001), AAT (r = 0.49, p < 0.001), APT (r = 0.51, p < 0.001), and MST (r = 0.40, p < 0.001). SF‐36's RP scale correlated with AA6M (r = 0.37, p < 0.001), AAT (r = 0.38, p < 0.001), APT (r = 0.44, p < 0.001), and MST (r = 0.33, p < 0.001). SF‐36's BP scale correlated with AA6M (r = 0.50, p < 0.001), AAT (r = 0.48, p < 0.001), APT (r = 0.59, p < 0.001), and MST (r = 0.42, p < 0.001). CONCLUSION: The SF‐36's BP domain resulted in the highest correlation with RADAR items. The APT item of RADAR had the highest correlation with all three domains of SF‐36. These results suggest that the level of bodily pain is indicative of functioning and well‐being of patients.

BACKGROUND: Both physician‐assessed and patient self‐reported joint counts have been used in the assessment of disease activity in rheumatoid arthritis. The objective of this study was to compare patient vs. physician reported joint counts in patients with new onset RA. METHODS: Baseline data was analyzed from the Study of New Onset Rheumatoid Arthritis (S.O.N.O.R.A.SM), a five‐year prospective, longitudinal, inception cohort study to document long‐term functional, clinical, and humanistic outcomes and patterns of treatment in patients with new onset RA. Baseline data collection consisted of physician and patient surveys. Physicians assessed swollen (SJ) and tender/painful joints (TJ) while patients reported painful joint (PJ). Physician's SJ and TJ consisted of examination in 64 and 66 joints, respectively. Patient's PJ was assessed in 16 joint areas with use of a mannequin. The Pearson product moment correlation coefficient was calculated for SJ, TJ, and PJ counts. RESULTS: One hundred and seven patients completed the baseline survey. Mean age of the sample was 55 ± 15 years; 79% were female; 80% were Caucasian. Mean joint counts were 12.6 (SE = 0.9) SJ, 14.0 (SE = 1.3) TJ, and 6.6 (SE = 0.4) PJ. Patient‐reported PJ correlated with physician‐reported SJ (r = 0.22, p = 0.023) and TJ (r = 0.55, p < 0.001). CONCLUSION: Higher correlation was observed between PJ and TJ compared to SJ. Patient, self‐reported joint counts may be a useful surrogate of joint activity in the absence of physician assessment. However, caution should be taken given that the accuracy of patient, self‐reported joint counts still needs further evaluation. Five‐year follow‐up of this population will provide further insight on the sensitivity to change for both patient and physician reported joint counts as it relates to disease activity.