Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance

Abstract

Background: In patients with rheumatoid arthritis (RA), persistent inflammation and increasing disease activity are associated with increased risk of adverse events (AEs). Objectives: To assess relationships between RA disease activity and AEs of interest in patients treated with tofacitinib or tumor necrosis factor inhibitors (TNFi). Design: This was a post hoc analysis of a long-term, postauthorization safety endpoint trial of tofacitinib versus TNFi. Methods: In ORAL Surveillance, 4362 patients aged ⩾50 years with active RA despite methotrexate, and ⩾1 additional cardiovascular (CV) risk factor, were randomized 1:1:1 to tofacitinib 5 or 10 mg twice daily or TNFi for up to 72 months. Post hoc time-dependent multivariable Cox analysis evaluated the relationships between disease activity [Clinical Disease Activity Index (CDAI)], inflammation [C-reactive protein (CRP)], and AEs of interest. The AEs included major adverse CV events (MACE), malignancies excluding nonmelanoma skin cancer (NMSC), venous thromboembolism (VTE), serious infections, herpes zoster (HZ), nonserious infections excluding HZ (NSI), and death. Results: Across treatments, risk for NSI was higher when patients had CDAI-defined active disease versus remission; MACE and VTE risks trended higher, but did not reach significance. Hazard ratios for MACE, malignancies excluding NMSC, VTE, infections, and death rose by 2–9% for each 5-mg/L increment in serum CRP. The interaction terms evaluating the impact of treatment assignment on the relationship between disease activity and AEs were all p > 0.05. Conclusion: In ORAL Surveillance, higher NSI risk was observed in the presence of active RA versus remission. The risk of MACE and VTE directionally increased in active disease versus remission, although statistical power was limited due to small event numbers in these categories. The relationship between active disease and AEs was not impacted by treatment with tofacitinib versus TNFi. Registration: NCT02092467.

Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data

“…Notably, markers of disease activity have been associated with CV risk in RA, PsA, and AS [ 51 – 54 ]. In ORAL Surveillance, risk of MACE and VTE was numerically higher in patients with active disease (low, medium, or high disease activity) versus those in remission [ 55 ]. Accordingly, the European Alliance of Associations for Rheumatology recommendations emphasize the importance of optimal control of disease activity in patients with inflammatory joint disorders to reduce CV risk [ 10 ].…”

Tofaticinib as a potential therapeutic agent: a review

“…In rare cases tofacitinib therapy has also led to shingles, rash and anemia. 25,26 FDA have mandated a box warning on the label of tofacitinib about the possible adverse events including bacterial, viral or fungal infections, TB and hepatic toxicity. [25][26][27]…”

“…27,28 TOXICITY Tofacitinib therapy should be cautiously used in females of reproductive age as the therapy may lead to a possible risk to developing foetus, also breast feeding for 18 to 36 months is not recommended for lactating mothers on tofacitinib therapy. [25][26][27][28] Tofacitinib therapy may also lead to infertility in women of reproductive age. Tofacitinib therapy may also elevate the chances of bacterial, fungal and viral infections or TB leading to hospitalization and mortality.…”

“…Lymphomas and malignancy are possible toxic effects of tofacitinib therapy. [23][24][25][26][27] Tofacitinib therapy may cause lymphoproliferative disorder in patients receiving renal transplant. 28…”

“…Immunosuppressants like cyclosporines, tacrolimus, azathioprine or biologic DMARDs like etanercept, abatacept, adalimumab, infliximab, rituximab, tocilizumab, certolizumab, golimumab, ustekinuma, secukinumab, vedolizumab, ixekizumab, anakinra are not recommended concomitantly with tofacitinib therapy as it may increase the risk of infection. [25][26][27][28][29] Administration of vaccine alongside, before or soon after tofacitinib therapy is not recommended as tofacitinib therapy may decrease the effectiveness of vaccines. 28,29…”