BIRMINGHAM, ENGLAND – Patients being treated with biologics for rheumatoid arthritis have a low risk for developing opportunistic infections, based on a new analysis of data from one of the largest and longest running biologics registers.
Data on 19,162 patients included in the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) showed that the incidence rate of opportunistic infections was 1.33 cases per 1,000 patient years when using any biologic drug, including anti–tumor necrosis factor (anti-TNF) drugs, rituximab (Rituxan/MabThera), or the interleukin-6 receptor inhibitor tocilizumab (Actemra).
Incidence rates for opportunistic infections appeared to be lowest with tocilizumab at 0.88 per 1,000 patient years, although the duration of follow-up with this drug was the shortest. Rates for anti-TNF drugs as a whole and rituximab were a respective 1.30 and 1.58 per 1,000 patient years.
“Opportunistic infections remain very rare events,” said Dr. Andrew Rutherford, a rheumatology clinical fellow at King’s College London, England.
The potential for serious infections to develop with biologic treatment is well known, and several analyses have already been performed on the BSRBR-RA data, Dr. Rutherford acknowledged at the British Society for Rheumatology annual conference. However, these prior analyses have become somewhat outdated and don’t reflect current practice or the current cohort of patients starting biologic therapy, he said.
“Using the old comparator arm of continuing patients on DMARD [disease-modifying anti-rheumatic drug] therapy isn’t really relevant for us in clinical practice any more,” he said. “I think for the majority of us, when we’re faced with a patient who’s got high disease activity, we are going to start them on a biologic, and the question is ‘Which biologic is safest or most effective?’ as opposed to ‘Should they just remain on DMARDs?’ ”
Patients currently starting biologic treatments who are included in the Register are also less likely to have been treated with steroids and more likely to have been diagnosed with RA for less than 5 years. Then, there are the newer biologics, such as tocilizumab and even more recently the Janus kinase (JAK) inhibitors.
“So, I think, clearly, there is a need to do updated analyses using the BSRBR,” Dr. Rutherford reasoned.
In the current analysis, which covers more than 99,000 patient years of follow-up overall, the primary aim was to estimate the incidence of opportunistic infections other than tuberculosis (TB) by biologic drug class.
Of 106 cases of opportunistic infections seen in patients treated with anti-TNF drugs, most (48%) resulted from herpes zoster, Pneumocystis pneumonia (PCP; 11.3%), or Aspergillus (11.3%).
There were 24 opportunistic infections in patients treated with rituximab, of which PCP (33.3%) or herpes zoster (29%) were the most common causes.
There were just three opportunistic infections in patients treated with tocilizumab, which were all different organisms, Dr. Rutherford reported.
Using anti-TNF therapy as the control, the unadjusted and adjusted hazard ratios for an opportunistic infection were a respective 1.21 and 0.92 for rituximab and 0.60 and 0.28 for tocilizumab. The confidence intervals were wide, however, crossing 1.0 in all comparisons, Dr. Rutherford emphasized.
PCP is rare with all biologics, but the incidence was almost four-times higher (HR, 3.91) with rituximab versus anti-TNF therapy, but the 95% CIs were wide (1.60–9.92) and probably not enough to influence practice.
A secondary analysis also looked at the incidence of TB by biologic drug class, although this was originally excluded from the study design. Not only has it been previously reported on from BSRBR, “guidelines have come into place that have probably changed the rates of TB dramatically over the years,” Dr. Rutherford said, so comparing older and new cohorts of biologic-treated patients might be “a little bit unfair.”
The incidence of TB per 100,000 patient years was 67.8 for all anti-TNF therapies, with a lower rate seen with rituximab (13.2 per 100,000 patient years) than any individual anti-TNF drug (48.9 for etanercept, 75.5 for infliximab, 84.6 for adalimumab, and 99.0 for certolizumab per 100,000 patient years).
These rates might potentially influence the choice of drug for a patient with a high-risk for reactivation of TB, Dr. Rutherford suggested.
Overall, rates of TB have fallen year over year in the Register. However, that likely reflects better screening and treatment of the infection, he added.
The BSRBR-RA is funded by the BSR through restricted grants from UK pharmaceutical companies. Past and present participating companies include Abbvie, Celltrion, Hospira, Pfizer, UCB, Roche, Merck and Samsung. Dr. Rutherford had no conflicts of interest.