A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA (R)) to the reference product (Humira (R)) in patients with active rheumatoid arthritis

Background: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA (R), CinnaGen, Iran) to the innovator product (Humira (R), AbbVie, USA) in adult patients with active rheumatoid arthritis (RA). Methods: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA (R) or Humira (R) every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety. Results: Patients who were randomized to CinnoRA (R) or Humira (R) arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA (R) group was non-inferior to the Humira (R) group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA (R) and Humira (R) groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant. Conclusion: CinnoRA (R) was shown to be non-inferior to Humira (R) in terms of efficacy at week 24 with a comparable safety profile to the reference product

Secondary Sjogren's Syndrome in 83 Patients With Rheumatoid Arthritis

Sjogren syndrome (SS) can occur alone, primary Sjogren syndrome, or in association with other rheumatic diseases, secondary Sjogren syndrome (sSS), such as Rheumatoid arthritis (RA). The occurrence of Sjogren syndrome with RA makes it course worse and increases high morbidity and mortality of RA. In this exploratory study we aim to determine the prevalence of sSS (diagnosed based on the revised version of American–European consensus Group Classification Criteria: AUCG-criteria), sicca symptoms (dry eye, dry mouth), positive autoantibody tests (Anti RO or Anti-LA antibodies), UWSFR (Unstimulated Whole Salivary Flow Rate), Schirmer and Lissamine test. In this cross-sectional study, eighty three consecutive RA patients (according to American College of Rheumatology criteria 1987) who were visited at rheumatology clinic of Razi General Hospital located in the north of Iran entered into our study. Our exclusion criteria was a positive history of past head and neck radiation treatment, Hepatitis C infection, acquired immunodeficiency disease (AIDS), pre-existing lymphoma, sarcoidosis, graft versus host disease, use of anticholinergic drugs (including neuroleptics, antidepressants, antihypertensive and parasympatholytics). They examined with UWSFR by a rheumatologist and with Schirmer test and Lissamine test by an ophthalmologist. Participants were 90.4% female with the mean age 48.3±13 years. Duration of RA was in 36.1% less than 5 years, in 22.9% 5-10 years, in 12.1% 11-15 years and in 28.9% more than 15 years. Our results demonstrated that the prevalence of sSS was 5.9% (CI:0.6%-10.5%). Number of 27.7% of RA patients positively responded to at least one question about sicca symptoms. Among objective tests, only Positive UWSFR and Lissamine test were significantly more common in RA patients with sSS in comparison to ones without sSS (P<0.001, P=0.01 respectively). In RA patients, we found a linear trend between sicca symptoms and aging (P=0.02). In patients with sicca symptoms, among tests that used for assessing decrease in saliva or tear production, only USWFR significantly more common (P=0.01). In conclusion: In RA population in North of Iran prevalence of sSS was less than 10%. In them, a significant linear trend existed between aging and sicca symptoms. Among objective tests of AUCG-criteria (except for lip biopsy that was not performed in the current study) only UWSFR and Lissamine test were significantly more common in patients with sSS in comparison ones without it

A Phase IV Study of the Safety and Efficacy of CinnoPar® in Iranian Patients with Osteoporosis

The safety of teriparatide has been studied in various phase III and phase IV trials. However, a postmarketing study of the biosimilar of teriparatide, CinnoPar®, has not been conducted on Iranian patients. This was a phase IV study conducted on osteoporotic patients who received an Iranian teriparatide biosimilar with a dose of 20 μg daily. The primary outcome of this study was to monitor for adverse events (AEs). Effectiveness as the secondary outcome was measured using the EQ-5D quality-of-life questionnaire and back pain Visual Analogue Scale (VAS) score. Among 193 analyzed patients between September 2015 and March 2019, the most common AEs were hypercalcemia (4%), nausea, and pain (3%). No deaths, serious AEs, or other significant AEs occurred in this study. The mean EQ-5D scores decreased after the course of the treatment from 2.3 ± 0.66 at the baseline to 2 ± 0.66. The mean back pain VAS scores also decreased from 4.9 ± 3.6 at baseline to 1.8 ± 2.1 at the end of the study. Both changes were statistically significant (p<0.001). Consistent with the findings of previous studies and the drug monograph, no new safety concern was observed with this biosimilar teriparatide, and the drug was effective based on the VAS score and EQ-5D in osteoporotic patients