Patient-Reported Outcomes of Baricitinib in Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment

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SCIENCE
Patient-Reported Outcomes of Baricitinib in Rheumatoid Arthritis and No or Limited Prior Disease-Modifying Antirheumatic Drug Treatment
Key Take-Away: 

Baricitinib alone or in combination with methotrexate, when used as initial therapyleads to a significant improvement in rheumatoid arthritis as compared to methotrexate alone.

Rheumatoid arthritis (RA) patients often suffer from number of restrictions in daily life due to frequent pain, fatigue, sleep disturbance and functional impairment in work and physical activities. 

ABSTRACT: 
Background: 

Rheumatoid arthritis (RA) patients often suffer from number of restrictions in daily life due to frequent pain, fatigue, sleep disturbance and functional impairment in work and physical activities.

Baricitinib is a selective JAK1 and JAK2 inhibitor approved in Europe for RA. Baricitinib interferes with JAK-STAT signaling pathways that further blocks the cytokine signaling that plays an important role in the pathogenesis of RA. RA-BEGIN was a phase III study (NCT01711359) conducted with active RA patients. Baricitinib alone or in combination with MTX demonstrated superior clinical efficacy with acceptable safety compared to MTX as the initial therapy for active RA. The present study reports the efficacy of baricitinib, administered as monotherapy or in combination with MTX compared to MTX monotherapy in RA.

Rationale behind the research

  • No statistically significant difference was assessed and compared between baricitinib as monotherapy and cobination with MTX against the RA in earlier studies.
  • Therefore, this study was conduct to compare the effectiveness of  baricitinib with MTX on the patient with RA and no prior DMARD therapy or limited prior MTX therapy.

Objective

The objective of this study was to evaluate and compare the efficacy of baricitinib as a monotherapy or in combination with MTX in RA.

Methods: 

 

Study outcomes measures

  • Visual Analog Scales (VAS): The Patient’s Global Assessment of Disease Activity (PtGA) and assessment of pain was evaluated using VAS.
  • Health Assessment Questionnaire-Disability Index (HAQ-DI): Physical function was assessed by HAQ-DI; scores range from 0 to 3, with lower scores reflecting better physical function and less disability.
  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale: Fatigue was assessed by the FACIT-F scale; scores range from 0 to 52, with higher scores representing less fatigue.
  • Duration of morning joint stiffness (MJS): It was reported by the patient as the length of time in minutes that joint stiffness lasted on the day prior to each study visit.
  • Numeric Rating Scales (NRS): Assessments of the worst joint pain and the worst tiredness over the past 24 hours were measured using novel Worst Joint Pain and Worst Tiredness NRS. Scores for both the NRSs range from 0 (no joint pain/tiredness) to 10 (“as bad as you can imagine”).
  • Health-related quality of life (HRQoL): It was evaluated using the Medical Outcomes Study (MOS) Short Form-36 (SF-36), physical and mental component scores (PCS) and EuroQol 5-Dimensions (EQ-5D) Health State Profile.
  • Overall work productivity: Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA) instrument was used to measure overall work productivity and impairment of regular activities during the past 7 days.
  • Time period: The PROs were assessed at baseline, week 1, week 2, week 4, and every 4 weeks thereafter to week 24; after week 24 they were assessed at weeks 32, 40, and 52; with the exception of the FACIT-F, which was assessed at baseline, week 1, week 4 and then followed the same schedule as the other PROs and the SF-36, EQ-5D, and WPAI-RA, which were assessed at baseline and week 4 and then followed the same schedule as the other PROs.
Results: 

 

Study Outcomes

  • HAQ-DI, PtGA: Improvements in both the baricitinib monotherapy and baricitinib + MTX groups were evident as early as week 1 compared to MTX. Significant improvements in physical function, PtGA and patient’s assessment of pain were maintained through week 24 to week 52.

At week 24 there were 70%, 81%, and 79% improvement in HAQ-DI scores that exceeded the MCID (≥ 0.22) patients with MTX, baricitinib monotherapy, and baricitinib + MTX, respectively and at week 52 there were 57%, 68%, and 72% (p ≤ 0.05 for baricitinib monotherapy vs. MTX; p ≤ 0.001 for baricitinib + MTX vs. MTX). The percentage of patients who achieved the normative value of ≤ 0.25 at week 24 for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively, were 21%, 33%, and 34% (p ≤ 0.05 for the baricitinib monotherapy vs. MTX; p ≤ 0.01 for baricitinib + MTX vs. MTX) and were 18%, 29%, and 34% (p ≤ 0.05 for the baricitinib monotherapy vs. MTX; p ≤ 0.001 for baricitinib + MTX vs. MTX) at week 52 (Figure 1,2).

Figure 1: Change from baseline at week 24 for patient-reported outcomes 

Figure 2: Change from baseline at week 52 for patient-reported outcomes

  • FACIT-F, duration of MJS: Significant improvement was observed in the FACIT-F for both the baricitinib monotherapy and combinational group at week 1 (p≤ 0.001 for both baricitinib groups vs. MTX). The duration of MJS, worst joint pain, and worst tiredness were significantly reduced in both baricitinib groups compared to MTX from week 1 and these improvements were maintained to week 24 and 52 in both baricitinib groups.

At week 24 there were 65%, 75%, and 71% improvement in the FACIT-F that exceed the MCID for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively. On the other hand at week 52 there were 54%, 62% and 62% improvement was observed for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively.

  • HRQoL: At week 4 there were statistically significant improvement in SF-36 and PCS were observed in both the baricitinib monotherapy and the baricitinib + MTX and these improvements were maintained and shows statistically significant results at weeks 40 and 52 also (p ≤ 0.05) .

There were 62%, 71%, and 74% improvement in SF-36 PCS at week 24 for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively. On the other hand, at week 52 the percentage of improvement were 48%, 65%, and 65% for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively.

Statistically significant improvement in EQ-5D UK index score in both the baricitinib monotherapy and baricitinib + MTX groups compared to MTX at wek 4 and which were maintained through week 52. Similarly at the begining of week 4, statistically significant improvement  was seen in the EQ-5D VAS in both baricitinib groups compared to the MTX group.

  • WPAI-RA: The baricitinib monotherapy and baricitinib + MTX groups showed significant improvement in WPAI-RA as compared with MTX montherapy group. These improvements were only maintained at week 52 in the baricitinib + MTX group compared to the MTX group, with respect to work productivity loss (p≤0.05) (Figure 3).

Figure 3: Impairment of regular activities among all patients at baseline and least-squares mean change from baseline at week 24 and at week 52 

Conclusion: 

This study concluded that baricitinib may either be used as monotherapy or in combination with MTX, for the treatment of RA. Beacuase of its effectiveness in controlling disease and improving the patient QoL, the ACR guidelines and EULAR recommend MTX as the first-line treatment for DMARD-naïve patients. Heijde et al in 2006 also known as TEMPO study showed that etanercept monotherapy had similar benefit to MTX monotherapy in improving PROs.

Many patients do not respond to MTX monotherapy or is unsuitable for them, thus, there is need for an alternativetherapy for these patients.

The present study reported the similar results as that of previous studies bDMARDs plus MTX in RA patients. A PREMIER study conducted by Breedveld et al in 2006 compare the adalimumab as monotherapy and in combination with MTX. In PREMIER, the baseline HAQ-DI values for MTX monotherapy, adalimumab monotherapy, and adalimumab + MTX were decreaed from 1.5, 1.6, and 1.5  to  − 0.8, − 0.8 and − 1.1 at 1 year. In the RA-BEGIN analysis, the mean baseline HAQ-DI scores for MTX, baricitinib monotherapy, and baricitinib + MTX, respectively, were 1.7, 1.6, and 1.6 with decrements of − 0.71, − 0.99 and − 1.06 at one year. A  2014 study by Lee et al known as ORAL start trial compared tofacitinib with MTX and found that on physical functioning,  tofacitinib exhibit more benifit than MTX monotherapy.

The PRO results of this study are similar to the results of the previous studies such as OPTIMA trial, which compared adalimumab with MTX in RA patients.

In the HRQOL assessments, both the baricitinib groups showed significant improvement in the EQ-5D index score, VAS score and SF-36 PCS as compared to the MTX monotherapy group. The SF-36 MCS results were similar with the previous clinical trials. In this study, all three treatment groups had shown effectiveness in improving the work impairment.

Arthritis research & therapy. 2017 Dec;19(1):208.

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