At this year’s 2020 American College of Rheumatology (ACR) virtual meeting, an array of new research abstracts for potential treatments were presented showing promising outcomes for those with spondyloarthritis. Following are summaries of five different research abstracts on medications studied for ankylosing spondylitis from this year’s conference.
XELJANZ®/XELJANZ® XR (Tofacitinib) for the Treatment of Adult Patients with Ankylosing Spondylitis: Primary Analysis of a Phase 3, Randomized, Double-blind, Placebo-controlled Study
To examine the safety and efficacy of the JAK inhibitor, tofacitinib (Xeljanz) in patients with ankylosing spondylitis (AS), a double-blind study was conducted, in which neither the participants nor the researchers know who is receiving the treatment medication. The study included adult-onset AS patients, who have had inadequate response or an intolerance to two or more nonsteroidal anti-inflammatory drugs (NSAIDs). Among the 239 participants, 133 were randomly selected to receive with the other 136 participants in the placebo group receiving an inactive substance (sugar pill). After 16 weeks, ALL participants received, and were told they were receiving, tofacitinib until the end of the 48-week trial.
Improvements in disease activity were significantly greater in those taking tofacitinib compared with those in the placebo group. At the end of week 16, 56.4% of the tofacitinib group vs 29.4% of the placebo group improved enough to achieve ASAS201, and 40.6% of the tofacitinib group vs 12.5% of the placebo group improved enough to achieve ASAS 402. These findings demonstrate a significant improvement with the treatment group in total back pain, morning stiffness, Patient’s Global Assessment of disease activity3, and Bath Ankylosing Spondylitis Functional Index score.4
Dr. Atul Deodhar a member of SAA’s Medical and Scientific Board, and contributing writer on this study stated, “The safety profile of tofacitinib in patients with ankylosing spondylitis was consistent with the known safety profile in patients with rheumatoid arthritis or psoriatic arthritis. No new potential safety risks were identified in patients with ankylosing spondylitis.”
In conclusion, the study determined that patients with active AS taking tofacitinib had rapid improvements in disease activity, with a significant difference demonstrated between the treatment group and the placebo group at week 16. Reactions and adverse effects (such as upper respiratory tract infection, nasopharyngitis, diarrhea etc.) were more frequent with tofacitinib vs placebo, but there were no new safety risks identified.
COSENTYX® (Secukinumab) 150 Mg Provides Sustained Relief in Total and Nocturnal Back Pain, Morning Stiffness, Fatigue, and Low Disease Activity in Patients with Active Ankylosing Spondylitis: End-of-study (5-year) Data from the MEASURE 2 Trial
An end-of-study analysis was conducted on a 5-year study, called “Measure 2” which analyzed the effects of treatment with 150mg of secukinumab (Cosentyx) compared to a Placebo Group (participants receiving an inactive substance.) This study confirmed that the participants being treated with 150 mg secukinumab felt less pain and stiffness even after 5 years of continuous treatment, compared to when they first enrolled in the study. The study reported maintaining clinically significant improvements in total back pain, nocturnal back pain, morning stiffness, fatigue, and disease activity in patients with active AS throughout the full 5 years of treatment with secukinumab.
In addition, sustained improvements were seen in both TNFi-naïve patients (those who’d never taken a TNFi medication before enrolling in the study) and those who’d had insufficient response to or were intolerant of another TNFi medication, with statistically higher sustained improvement in TNFi-naïve patients. This analysis demonstrated that people with AS treated with 150 mg secukinumab generally sustained improvements realized at week 16 through the 5th year of treatment with the medication.
Achievement of Partial Remission and Inactive Disease in Upadacitinib (RINVOQ™) Treated Patients with Ankylosing Spondylitis
In the SELECT-AXIS 1 study, participants with active AS with intolerance or inadequate response to two or more nonsteroidal anti-inflammatory drugs (NSAIDs), but who had not yet tried a biologic medication, were randomly assigned to two groups: a treatment group taking 15mg of upadacitinib (Rinvoq, a JAK inhibitor medication) taken once daily, and a placebo group (receiving inactive sugar pills).
After 14 weeks, 19% of those in the treatment group achieved ASAS Partial Remission10. At week 14, considerably more patients had an ASAS402 response in the upadacitinib group (52%) versus in the placebo group (26%). In addition, 33% of participants from the placebo group, who switched to receiving treatment after the 14-week mark, also achieved ASAS Partial Remission as early as 32 weeks into the study. The 44 total patients who achieved ASAS Partial Remission also achieved ASDAS Inactive Disease from both the continuous treatment group (69%) and the placebo to treatment group (57%). A consistent improvement was seen among those who achieved ASAS Partial Remission with upadacitinib treatment.
Effect of RINVOQ™ (Upadacitinib) on Reducing Pain in Patients with Active Ankylosing Spondylitis and Inadequate Response to Nonsteroidal Anti-inflammatory Drugs
In additional analysis the SELECT-AXIS 1 authors assessed the effects of 15mg of upadacitinib (Rinvoq) on pain levels in patients with active ankylosing spondylitis, using multiple pain assessment tools. The analysis concluded that a larger proportion of patients treated with upadacitinib achieved fast, substantial, and clinically meaningful reductions in pain vs the placebo group. In addition, the reductions in pain were sustained over time starting as early as two weeks into the study, and improving over time, demonstrating an increased response rate over time. Patients who switched from the placebo group to the treatment group at week 14 reached the same level of improvement in pain scores after switching, as the group taking upadacitinib to begin with.
Improvements in Global Functioning and Health-related Quality of Life and Their Association with Disease Activity and Functional Improvement in Patients with Active Ankylosing Spondylitis Treated with RINVOQ™ (Upadacitinib)
An additional, post-hoc analysis12 of the SELECT-AXIS 1 trial was done to evaluate the effect of 15 mg of upadacitinib (Rinvoq)on AS disease activity and physical function improvements. The Assessment of Spondyloarthritis international Society Health Index (ASAS HI)7 and Ankylosing Spondylitis Quality of Life (ASQoL)8 questionnaires were used to measure improvements in disease activity throughout the 14-week period. At week 14, significantly more patients in the upadacitinib group achieved the Minimum Clinically Important Difference (MCID)9 measure in ASAS HI7 (score ≤5) and ASQoL8 (score ≤8) than those in the placebo group (taking an inactive sugar pill). At Week 14, significantly more patients in the upadacitinib group achieved improvement of MCID9 ((≥3-point Improvement from Baseline to Week 14) in ASAS HI7 (upadacitinib (44.7%) vs. placebo (27%)) and ASQoL8 (upadacitinib (61.4%) vs. placebo (43%)). This analysis concluded that patients with active AS being treated with upadacitinib achieved clinically meaningful improvements compared with the placebo group in global functioning and health-related quality of life (HRQoL11) as measured by ASAS HI7 and ASQoL8.
Glossary:
[1] The ASAS Response Criteria (ASAS 20) is defined as an improvement of at least 20%, and an absolute improvement of at least 10 units on a 0-100 scale, in at least three of the following domains: Patient Global Assessment, Pain Assessment, Function (BASFI), and Inflammation (last 2 questions of BASDAI).
[2] The ASAS Response Criteria (ASAS 40) is defined as an improvement of at least 40%, and an absolute improvement of at least 10 units on a 0-100 scale, in at least three of the following domains: Patient Global Assessment, Pain Assessment, Function (BASFI), and Inflammation (last 2 questions of BASDAI).
[3] Patient Global Assessment (PGA) is one of the most widely used patient-reported outcomes in rheumatology practice and research and is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is often assessed by a single question with a 0–10 or 0–100 response.
[4] The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is an established self-administered measurement tool which allows a physician to determine the effectiveness of a current drug therapy by measuring severity of fatigue, spinal and peripheral joint pain, localized tenderness, and morning stiffness. Scores range from 0 (best) to 10 (worst); a score >4 indicates active disease.
[5] C-reactive protein (CRP) is a blood marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP is classified as an acute phase reactant, which means that its levels will rise in response to inflammation.
[6] The Ankylosing Spondylitis Disease Activity Score (ASDAS) is used to assess disease activity in the participants, which is defined as a decrease of at least two points from baseline (ASDAS-MI: ≥2.0) or lowest possible score (0.6).
[7] The ASAS Health Index (ASAS HI) has been developed under the auspices of the Assessment of Spondyloarthritis International Society (ASAS) to assess health in patients with all forms of spondyloarthritis (SpA) (specifically radiographic and non-radiographic axial SpA as well as peripheral SpA). The self-report questionnaire measures functioning and health across 17 aspects of health and 9 environmental factors (EF) in patients with SpA.
[8] Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire is a patient-reported outcome (PRO) measure which assesses the quality of life of patients with ankylosing spondylitis. The ASQoL is based on the needs-based quality of life model. It is a self-administered questionnaire which contains 18 items, total score ranging from 0 to 18 with lower scores indicating better HRQoL
[9] The Minimum Clinically Important Difference (MCID) represents the smallest improvement considered worthwhile by a patient. The concept of an MCID is offered as the new standard for determining effectiveness of a given treatment and describing patient satisfaction in reference to that treatment.
[10] ASAS partial remission (ASAS PR) is defined as a value of ≤2 (on a 0–10 scale) for four domains: patient global assessment of disease activity, pain, function (BASFI), and inflammation (mean of BASDAI questions 5 and 6).
[11] Health-related quality of life (HRQoL) is a multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning. It goes beyond direct measures of population health, life expectancy, and causes of death, and focuses on the impact health status has on quality of life.
[12] A post-hoc analysis involves looking at the data after a study has been concluded, and trying to find patterns that were not primary objectives of the study. In other words, all analyses that were not pre-planned and were conducted as additional analyses after completing the experiment are considered to be post-hoc analyses.
Medication List:
Tofacitinib (Janus kinase (JAK) inhibitor)
Tofacitinib, sold under the brand Xeljanz among others, is a Janus kinase (JAK) inhibitor medication that is taken orally, and currently used to treat rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. JAK inhibitors belong to a family of medicines called DMARDs (disease-modifying antirheumatic drugs). Janus kinase (JAK) inhibitors are a group of medications that inhibit activity and response of one or more of the Janus kinase enzymes (JAK1, JAK2, JAK3, and TYK2). These enzymes normally promote inflammation and autoimmunity.
Upadacitinib (Janus kinase (JAK) inhibitor)
Upadacitinib, sold under the brand name Rinvoq, is a Janus kinase (JAK) inhibitor medication that is taken orally, and is currently approved for the treatment of moderate to severe rheumatoid arthritis in adults where methotrexate did not work well or could not be tolerated. It is classified as a small molecule Disease-Modifying Anti-Rheumatic Drug (DMARD), rather than a biologic, and works by very specifically targeting and inhibiting the JAK1 enzyme’s inflammatory activity.
Secukinumab (IL-17 Inhibitor)
Secukinumab, sold under the brand name Cosentyx, is a biologic IL-17 inhibitor medication that works by binding to the inflammatory cytokines interleukin (IL)-17A and inhibiting the inflammation these cytokines set off. It is currently approved for the treatment of psoriasis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and psoriatic arthritis. Secukinumab is given as an injection under the skin (subcutaneous injection).
References:
Deodhar A, Sliwinska-Stanczyk P, Xu H, et al. Tofacitinib for the treatment of adult patients with ankylosing spondylitis: primary analysis of a phase 3, randomized, double-blind, placebo-controlled study. Presented at: ACR Convergence 2020; November 5-9, 2020. Abstract L11.
Deodhar A, Östör A, Maniccia A, Ganz F, Gao T, Chu A, Poddubnyy D. Achievement of Partial Remission and Inactive Disease in Upadacitinib-Treated Patients with Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/achievement-of-partial-remission-and-inactive-disease-in-upadacitinib-treated-patients-with-ankylosing-spondylitis/. Accessed December 17, 2020.
Kiltz U, Sieper J, Deodhar A, Zueger P, Song I, Chen N, van der Heijde D. Improvements in Global Functioning and Health-related Quality of Life and Their Association with Disease Activity and Functional Improvement in Patients with Active Ankylosing Spondylitis Treated with Upadacitinib [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/improvements-in-global-functioning-and-health-related-quality-of-life-and-their-association-with-disease-activity-and-functional-improvement-in-patients-with-active-ankylosing-spondylitis-treated-with/. Accessed December 16, 2020.
Deodhar A, Baraliakos X, McInnes I, de Vlam K, Bessette L, Maniccia A, Lippe R, Saffore C, Gao T, Song I, Östör A. Effect of Upadacitinib on Reducing Pain in Patients with Active Ankylosing Spondylitis and Inadequate Response to Nonsteroidal Anti-inflammatory Drugs [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/effect-of-upadacitinib-on-reducing-pain-in-patients-with-active-ankylosing-spondylitis-and-inadequate-response-to-nonsteroidal-anti-inflammatory-drugs/. Accessed December 16, 2020.
Marzo-Ortega H, Miceli-Richard C, Gill S, Magrey M, Machado P, Shete A, Wang J, Rohrer S, Deodhar A. Subcutaneous Secukinumab 150 Mg Provides Sustained Relief in Total and Nocturnal Back Pain, Morning Stiffness, Fatigue, and Low Disease Activity in Patients with Active Ankylosing Spondylitis: End-of-study (5-year) Data from the MEASURE 2 Trial [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/subcutaneous-secukinumab-150-mg-provides-sustained-relief-in-total-and-nocturnal-back-pain-morning-stiffness-fatigue-and-low-disease-activity-in-patients-with-active-ankylosing-spondylitis-end-of/. Accessed December 16, 2020.
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